In January, as Mississippi health officials planned for their incoming shipments of COVID-19 vaccine, they assessed the state’s most vulnerable: health care workers, of course, and elderly people in nursing homes. But among those who needed urgent protection from the virus ripping across the Magnolia State were 1 million Mississippians with obesity.

Obesity and weight-related illnesses have been deadly liabilities in the COVID era. A report released this month by the World Obesity Federation found that increased body weight is the second-greatest predictor of COVID-related hospitalization and death across the globe, trailing only old age as a risk factor.

As a fixture of life in the American South – home to 9 of the nation’s 12 heaviest states – obesity is playing a role not only in COVID outcomes, but in the calculus of the vaccination rollout. Mississippi was one of the first states to add a body mass index of 30 or more (a rough gauge of obesity tied to height and weight) to the list of qualifying medical conditions for a shot. About 40% of the state’s adults meet that definition, according to federal health survey data, and combined with the risk group already eligible for vaccination – residents 65 and older – that means fully half of Mississippi’s adults are entitled to vie for a restricted allotment of shots.

At least 29 states have green-lighted obesity for inclusion in the first phases of the vaccine rollout, according to KFF – a vast widening of eligibility that has the potential to overwhelm government efforts and heighten competition for scarce doses.

“We have a lifesaving intervention, and we don’t have enough of it,” said Jen Kates, PhD, director of global health and HIV policy for Kaiser Family Foundation. “Hard choices are being made about who should go first, and there is no right answer.”

The sheer prevalence of obesity in the nation – two in three Americans exceed what is considered a healthy weight – was a public health concern well before the pandemic. But COVID-19 dramatically fast-tracked the discussion from warnings about the long-term damage excess fat tissue can pose to heart, lung and metabolic functions to far more immediate threats.

In the United Kingdom, for example, overweight COVID patients were 67% more likely to require intensive care, and obese patients three times likelier, according to the World Obesity Federation report. A Centers for Disease Control and Prevention study released Monday found a similar trend among U.S. patients and noted that the risk of COVID-related hospitalization, ventilation and death increased with patients’ obesity level.

The counties that hug the southern Mississippi River are home to some of the most concentrated pockets of extreme obesity in the United States. Coronavirus infections began surging in Southern states early last summer, and hospitalizations rose in step.

Deaths in rural stretches of Arkansas, Louisiana, Mississippi, and Tennessee have been overshadowed by the sheer number of deaths in metropolitan areas like New York, Los Angeles, and Essex County, N.J. But as a share of the population, the coronavirus has been similarly unsparing in many Southern communities. In sparsely populated Claiborne County, Miss., on the floodplains of the Mississippi River, 30 residents – about 1 in 300 – had died as of early March. In East Feliciana Parish, La., north of Baton Rouge, with 106 deaths, about 1 in 180 had died by then.

“It’s just math. If the population is more obese and obesity clearly contributes to worse outcomes, then neighborhoods, cities, states and countries that are more obese will have a greater toll from COVID,” said Dr. James de Lemos, MD, a professor of internal medicine at UT Southwestern Medical Center in Dallas who led a study of hospitalized COVID patients published in the medical journal Circulation.

And, because in the U.S. obesity rates tend to be relatively high among African Americans and Latinos who are poor, with diminished access to health care, “it’s a triple whammy,” Dr. de Lemos said. “All these things intersect.”

Poverty and limited access to medical care are common features in the South, where residents like Michelle Antonyshyn, a former registered nurse and mother of seven in Salem, Ark., say they are afraid of the virus. Ms. Antonyshyn, 49, has obesity and debilitating pain in her knees and back, though she does not have high blood pressure or diabetes, two underlying conditions that federal health officials have determined are added risk factors for severe cases of COVID-19.

Still, she said, she “was very concerned just knowing that being obese puts you more at risk for bad outcomes such as being on a ventilator and death.” As a precaution, Ms. Antonyshyn said, she and her large brood locked down early and stopped attending church services in person, watching online instead.

“It’s not the same as having fellowship, but the risk for me was enough,” said Ms. Antonyshyn.

Governors throughout the South seem to recognize that weight can contribute to COVID-19 complications and have pushed for vaccine eligibility rules that prioritize obesity. But on the ground, local health officials are girding for having to tell newly eligible people who qualify as obese that there aren’t enough shots to go around.

In Port Gibson, Miss., Mheja Williams, MD, medical director of the Claiborne County Family Health Center, has been receiving barely enough doses to inoculate the health workers and oldest seniors in her county of 9,600. One week in early February, she received 100 doses.

Obesity and extreme obesity are endemic in Claiborne County, and health officials say the “normalization” of obesity means people often don’t register their weight as a risk factor, whether for COVID or other health issues. The risks are exacerbated by a general flouting of pandemic etiquette: Dr. Williams said that middle-aged and younger residents are not especially vigilant about physical distancing and that mask use is rare.

The rise of obesity in the United States is well documented over the past half-century, as the nation turned from a diet of fruits, vegetables and limited meats to one laden with ultra-processed foods and rich with salt, fat, sugar, and flavorings, along with copious amounts of meat, fast food, and soda. The U.S. has generally led the global obesity race, setting records as even toddlers and young children grew implausibly, dangerously overweight.

Well before COVID, obesity was a leading cause of preventable death in the United States. The National Institutes of Health declared it a disease in 1998, one that fosters heart disease, stroke, type 2 diabetes, and breast, colon, and other cancers.

Researchers say it is no coincidence that nations like the United States, the United Kingdom, and Italy, with relatively high obesity rates, have proved particularly vulnerable to the novel coronavirus.

They believe the virus may exploit underlying metabolic and physiological impairments that often exist in concert with obesity. Extra fat can lead to a cascade of metabolic disruptions, chronic systemic inflammation, and hormonal dysregulation that may thwart the body’s response to infection.

Other respiratory viruses, like influenza and SARS, which appeared in China in 2002, rely on cholesterol to spread enveloped RNA virus to neighboring cells, and researchers have proposed that a similar mechanism may play a role in the spread of the novel coronavirus.

There are also practical problems for coronavirus patients with obesity admitted to the hospital. They can be more difficult to intubate because of excess central weight pressing down on the diaphragm, making breathing with infected lungs even more difficult.

Physicians who specialize in treating patients with obesity say public health officials need to be more forthright and urgent in their messaging, telegraphing the risks of this COVID era.

“It should be explicit and direct,” said Fatima Stanford, MD, an obesity medicine specialist at Massachusetts General Hospital, Boston, and a Harvard Medical School instructor.

Dr. Stanford denounces the fat-shaming and bullying that people with obesity often experience. But telling patients – and the public – that obesity increases the risk of hospitalization and death is crucial, she said.

“I don’t think it’s stigmatizing,” she said. “If you tell them in that way, it’s not to scare you, it’s just giving information. Sometimes people are just unaware.”



KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

In January, as Mississippi health officials planned for their incoming shipments of COVID-19 vaccine, they assessed the state’s most vulnerable: health care workers, of course, and elderly people in nursing homes. But among those who needed urgent protection from the virus ripping across the Magnolia State were 1 million Mississippians with obesity.

Obesity and weight-related illnesses have been deadly liabilities in the COVID era. A report released this month by the World Obesity Federation found that increased body weight is the second-greatest predictor of COVID-related hospitalization and death across the globe, trailing only old age as a risk factor.

As a fixture of life in the American South – home to 9 of the nation’s 12 heaviest states – obesity is playing a role not only in COVID outcomes, but in the calculus of the vaccination rollout. Mississippi was one of the first states to add a body mass index of 30 or more (a rough gauge of obesity tied to height and weight) to the list of qualifying medical conditions for a shot. About 40% of the state’s adults meet that definition, according to federal health survey data, and combined with the risk group already eligible for vaccination – residents 65 and older – that means fully half of Mississippi’s adults are entitled to vie for a restricted allotment of shots.

At least 29 states have green-lighted obesity for inclusion in the first phases of the vaccine rollout, according to KFF – a vast widening of eligibility that has the potential to overwhelm government efforts and heighten competition for scarce doses.

“We have a lifesaving intervention, and we don’t have enough of it,” said Jen Kates, PhD, director of global health and HIV policy for Kaiser Family Foundation. “Hard choices are being made about who should go first, and there is no right answer.”

The sheer prevalence of obesity in the nation – two in three Americans exceed what is considered a healthy weight – was a public health concern well before the pandemic. But COVID-19 dramatically fast-tracked the discussion from warnings about the long-term damage excess fat tissue can pose to heart, lung and metabolic functions to far more immediate threats.

In the United Kingdom, for example, overweight COVID patients were 67% more likely to require intensive care, and obese patients three times likelier, according to the World Obesity Federation report. A Centers for Disease Control and Prevention study released Monday found a similar trend among U.S. patients and noted that the risk of COVID-related hospitalization, ventilation and death increased with patients’ obesity level.

The counties that hug the southern Mississippi River are home to some of the most concentrated pockets of extreme obesity in the United States. Coronavirus infections began surging in Southern states early last summer, and hospitalizations rose in step.

Deaths in rural stretches of Arkansas, Louisiana, Mississippi, and Tennessee have been overshadowed by the sheer number of deaths in metropolitan areas like New York, Los Angeles, and Essex County, N.J. But as a share of the population, the coronavirus has been similarly unsparing in many Southern communities. In sparsely populated Claiborne County, Miss., on the floodplains of the Mississippi River, 30 residents – about 1 in 300 – had died as of early March. In East Feliciana Parish, La., north of Baton Rouge, with 106 deaths, about 1 in 180 had died by then.

“It’s just math. If the population is more obese and obesity clearly contributes to worse outcomes, then neighborhoods, cities, states and countries that are more obese will have a greater toll from COVID,” said Dr. James de Lemos, MD, a professor of internal medicine at UT Southwestern Medical Center in Dallas who led a study of hospitalized COVID patients published in the medical journal Circulation.

And, because in the U.S. obesity rates tend to be relatively high among African Americans and Latinos who are poor, with diminished access to health care, “it’s a triple whammy,” Dr. de Lemos said. “All these things intersect.”

Poverty and limited access to medical care are common features in the South, where residents like Michelle Antonyshyn, a former registered nurse and mother of seven in Salem, Ark., say they are afraid of the virus. Ms. Antonyshyn, 49, has obesity and debilitating pain in her knees and back, though she does not have high blood pressure or diabetes, two underlying conditions that federal health officials have determined are added risk factors for severe cases of COVID-19.

Still, she said, she “was very concerned just knowing that being obese puts you more at risk for bad outcomes such as being on a ventilator and death.” As a precaution, Ms. Antonyshyn said, she and her large brood locked down early and stopped attending church services in person, watching online instead.

“It’s not the same as having fellowship, but the risk for me was enough,” said Ms. Antonyshyn.

Governors throughout the South seem to recognize that weight can contribute to COVID-19 complications and have pushed for vaccine eligibility rules that prioritize obesity. But on the ground, local health officials are girding for having to tell newly eligible people who qualify as obese that there aren’t enough shots to go around.

In Port Gibson, Miss., Mheja Williams, MD, medical director of the Claiborne County Family Health Center, has been receiving barely enough doses to inoculate the health workers and oldest seniors in her county of 9,600. One week in early February, she received 100 doses.

Obesity and extreme obesity are endemic in Claiborne County, and health officials say the “normalization” of obesity means people often don’t register their weight as a risk factor, whether for COVID or other health issues. The risks are exacerbated by a general flouting of pandemic etiquette: Dr. Williams said that middle-aged and younger residents are not especially vigilant about physical distancing and that mask use is rare.

The rise of obesity in the United States is well documented over the past half-century, as the nation turned from a diet of fruits, vegetables and limited meats to one laden with ultra-processed foods and rich with salt, fat, sugar, and flavorings, along with copious amounts of meat, fast food, and soda. The U.S. has generally led the global obesity race, setting records as even toddlers and young children grew implausibly, dangerously overweight.

Well before COVID, obesity was a leading cause of preventable death in the United States. The National Institutes of Health declared it a disease in 1998, one that fosters heart disease, stroke, type 2 diabetes, and breast, colon, and other cancers.

Researchers say it is no coincidence that nations like the United States, the United Kingdom, and Italy, with relatively high obesity rates, have proved particularly vulnerable to the novel coronavirus.

They believe the virus may exploit underlying metabolic and physiological impairments that often exist in concert with obesity. Extra fat can lead to a cascade of metabolic disruptions, chronic systemic inflammation, and hormonal dysregulation that may thwart the body’s response to infection.

Other respiratory viruses, like influenza and SARS, which appeared in China in 2002, rely on cholesterol to spread enveloped RNA virus to neighboring cells, and researchers have proposed that a similar mechanism may play a role in the spread of the novel coronavirus.

There are also practical problems for coronavirus patients with obesity admitted to the hospital. They can be more difficult to intubate because of excess central weight pressing down on the diaphragm, making breathing with infected lungs even more difficult.

Physicians who specialize in treating patients with obesity say public health officials need to be more forthright and urgent in their messaging, telegraphing the risks of this COVID era.

“It should be explicit and direct,” said Fatima Stanford, MD, an obesity medicine specialist at Massachusetts General Hospital, Boston, and a Harvard Medical School instructor.

Dr. Stanford denounces the fat-shaming and bullying that people with obesity often experience. But telling patients – and the public – that obesity increases the risk of hospitalization and death is crucial, she said.

“I don’t think it’s stigmatizing,” she said. “If you tell them in that way, it’s not to scare you, it’s just giving information. Sometimes people are just unaware.”



KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

In January, as Mississippi health officials planned for their incoming shipments of COVID-19 vaccine, they assessed the state’s most vulnerable: health care workers, of course, and elderly people in nursing homes. But among those who needed urgent protection from the virus ripping across the Magnolia State were 1 million Mississippians with obesity.

Obesity and weight-related illnesses have been deadly liabilities in the COVID era. A report released this month by the World Obesity Federation found that increased body weight is the second-greatest predictor of COVID-related hospitalization and death across the globe, trailing only old age as a risk factor.

As a fixture of life in the American South – home to 9 of the nation’s 12 heaviest states – obesity is playing a role not only in COVID outcomes, but in the calculus of the vaccination rollout. Mississippi was one of the first states to add a body mass index of 30 or more (a rough gauge of obesity tied to height and weight) to the list of qualifying medical conditions for a shot. About 40% of the state’s adults meet that definition, according to federal health survey data, and combined with the risk group already eligible for vaccination – residents 65 and older – that means fully half of Mississippi’s adults are entitled to vie for a restricted allotment of shots.

At least 29 states have green-lighted obesity for inclusion in the first phases of the vaccine rollout, according to KFF – a vast widening of eligibility that has the potential to overwhelm government efforts and heighten competition for scarce doses.

“We have a lifesaving intervention, and we don’t have enough of it,” said Jen Kates, PhD, director of global health and HIV policy for Kaiser Family Foundation. “Hard choices are being made about who should go first, and there is no right answer.”

The sheer prevalence of obesity in the nation – two in three Americans exceed what is considered a healthy weight – was a public health concern well before the pandemic. But COVID-19 dramatically fast-tracked the discussion from warnings about the long-term damage excess fat tissue can pose to heart, lung and metabolic functions to far more immediate threats.

In the United Kingdom, for example, overweight COVID patients were 67% more likely to require intensive care, and obese patients three times likelier, according to the World Obesity Federation report. A Centers for Disease Control and Prevention study released Monday found a similar trend among U.S. patients and noted that the risk of COVID-related hospitalization, ventilation and death increased with patients’ obesity level.

The counties that hug the southern Mississippi River are home to some of the most concentrated pockets of extreme obesity in the United States. Coronavirus infections began surging in Southern states early last summer, and hospitalizations rose in step.

Deaths in rural stretches of Arkansas, Louisiana, Mississippi, and Tennessee have been overshadowed by the sheer number of deaths in metropolitan areas like New York, Los Angeles, and Essex County, N.J. But as a share of the population, the coronavirus has been similarly unsparing in many Southern communities. In sparsely populated Claiborne County, Miss., on the floodplains of the Mississippi River, 30 residents – about 1 in 300 – had died as of early March. In East Feliciana Parish, La., north of Baton Rouge, with 106 deaths, about 1 in 180 had died by then.

“It’s just math. If the population is more obese and obesity clearly contributes to worse outcomes, then neighborhoods, cities, states and countries that are more obese will have a greater toll from COVID,” said Dr. James de Lemos, MD, a professor of internal medicine at UT Southwestern Medical Center in Dallas who led a study of hospitalized COVID patients published in the medical journal Circulation.

And, because in the U.S. obesity rates tend to be relatively high among African Americans and Latinos who are poor, with diminished access to health care, “it’s a triple whammy,” Dr. de Lemos said. “All these things intersect.”

Poverty and limited access to medical care are common features in the South, where residents like Michelle Antonyshyn, a former registered nurse and mother of seven in Salem, Ark., say they are afraid of the virus. Ms. Antonyshyn, 49, has obesity and debilitating pain in her knees and back, though she does not have high blood pressure or diabetes, two underlying conditions that federal health officials have determined are added risk factors for severe cases of COVID-19.

Still, she said, she “was very concerned just knowing that being obese puts you more at risk for bad outcomes such as being on a ventilator and death.” As a precaution, Ms. Antonyshyn said, she and her large brood locked down early and stopped attending church services in person, watching online instead.

“It’s not the same as having fellowship, but the risk for me was enough,” said Ms. Antonyshyn.

Governors throughout the South seem to recognize that weight can contribute to COVID-19 complications and have pushed for vaccine eligibility rules that prioritize obesity. But on the ground, local health officials are girding for having to tell newly eligible people who qualify as obese that there aren’t enough shots to go around.

In Port Gibson, Miss., Mheja Williams, MD, medical director of the Claiborne County Family Health Center, has been receiving barely enough doses to inoculate the health workers and oldest seniors in her county of 9,600. One week in early February, she received 100 doses.

Obesity and extreme obesity are endemic in Claiborne County, and health officials say the “normalization” of obesity means people often don’t register their weight as a risk factor, whether for COVID or other health issues. The risks are exacerbated by a general flouting of pandemic etiquette: Dr. Williams said that middle-aged and younger residents are not especially vigilant about physical distancing and that mask use is rare.

The rise of obesity in the United States is well documented over the past half-century, as the nation turned from a diet of fruits, vegetables and limited meats to one laden with ultra-processed foods and rich with salt, fat, sugar, and flavorings, along with copious amounts of meat, fast food, and soda. The U.S. has generally led the global obesity race, setting records as even toddlers and young children grew implausibly, dangerously overweight.

Well before COVID, obesity was a leading cause of preventable death in the United States. The National Institutes of Health declared it a disease in 1998, one that fosters heart disease, stroke, type 2 diabetes, and breast, colon, and other cancers.

Researchers say it is no coincidence that nations like the United States, the United Kingdom, and Italy, with relatively high obesity rates, have proved particularly vulnerable to the novel coronavirus.

They believe the virus may exploit underlying metabolic and physiological impairments that often exist in concert with obesity. Extra fat can lead to a cascade of metabolic disruptions, chronic systemic inflammation, and hormonal dysregulation that may thwart the body’s response to infection.

Other respiratory viruses, like influenza and SARS, which appeared in China in 2002, rely on cholesterol to spread enveloped RNA virus to neighboring cells, and researchers have proposed that a similar mechanism may play a role in the spread of the novel coronavirus.

There are also practical problems for coronavirus patients with obesity admitted to the hospital. They can be more difficult to intubate because of excess central weight pressing down on the diaphragm, making breathing with infected lungs even more difficult.

Physicians who specialize in treating patients with obesity say public health officials need to be more forthright and urgent in their messaging, telegraphing the risks of this COVID era.

“It should be explicit and direct,” said Fatima Stanford, MD, an obesity medicine specialist at Massachusetts General Hospital, Boston, and a Harvard Medical School instructor.

Dr. Stanford denounces the fat-shaming and bullying that people with obesity often experience. But telling patients – and the public – that obesity increases the risk of hospitalization and death is crucial, she said.

“I don’t think it’s stigmatizing,” she said. “If you tell them in that way, it’s not to scare you, it’s just giving information. Sometimes people are just unaware.”



KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

The lungs Bill Thompson was born with told a gruesome, harrowing and unmistakable tale to Dr. Anthony Szema when he analyzed them and found the black spots, scarring, partially combusted jet fuel and metal inside.

The retired Army staff sergeant had suffered catastrophic lung damage from breathing incinerated waste burned in massive open-air pits and probably other irritants during his tour of duty in Iraq.

“There’s black spots that are burns, particles all over; there’s metal. It was all scarred,” said Szema, a pulmonologist and professor who studies toxic exposures and examined Thompson’s preserved lung tissue. “There was no gas exchange anywhere in that lung.”

Thompson is still alive, surviving on his second transplanted set of lungs. Yet the story burned into the veteran’s internal organs is not one that has been entirely convincing to the U.S. government.

The military has not linked the burn pits to illness. That means many who were exposed to burn pits and are sick do not qualify for benefits under any existing program.

Retirement and health benefits for members of the military depend on factors like length of service, active or reserve status, deployments to combat zones and whether the military considers specific injuries or illnesses to be service-related. Thompson has been able to get care through the Department of Veterans Affairs for his lung disease but has not been able to secure other benefits, like early retirement pay.

“I was denied my Army retirement because if it was not a combat action, then I don’t receive that retirement,” Thompson said at a Senate Veterans’ Affairs Committee hearing last week on service members’ exposures to toxic substances.

Thompson is one of at least 3.5 million veterans since 2001 who have served in war zones where the U.S. military decided to dispose of its trash by burning it, according to VA estimates.

It’s not clear how many people within that population have gotten sick from exposure. Only a small fraction — 234,000 — have enrolled in the VA’s online burn pit registry. Veterans’ advocacy groups have said the majority of claims to the agency stemming from toxic exposures are denied, even as most former service members report contacts with toxins in their deployments.

Soldiers returning from tours in the global war on terror have reported debilitating illnesses almost from its beginning, but got little traction with the military. This year, though, the likelihood of congressional action is high, with Democrats expressing interest and a president who suspects burn pits are to blame for his son’s death.

President Joe Biden’s son Beau died of brain cancer in 2015 at age 46. He had deployed to Iraq in two sites with burn pits — at Baghdad and Balad — around the same time Thompson was at Camp Striker, near the Baghdad airport.

“Because of exposure to burn pits — in my view, I can’t prove it yet — he came back with stage 4 glioblastoma,” Biden said in a 2019 speech.

In testimony at the March 10 hearing, Shane Liermann, who works for the group Disabled American Veterans, told the committee that 78% of burn pit claims are denied. “Part of the problem is VA is not recognizing that exposure as being toxic exposures,” Liermann said.

Aleks Morosky, with the Wounded Warrior Project, said that in his group’s survey of 28,000 veterans last year, 71% said they had “definitely” been exposed to toxic substances or hazardous chemicals, and 18% said they had “probably” been exposed. Half of those people rated their health as poor or fair. Only about 16% of the service members who believed they had suffered exposure said they got treatment from the VA, and 11% said they were denied treatment.

Thompson, who is 49, said care for his lung disease is often slow and sometimes denied. It took the VA three years to approve an air purifier for his home to filter out allergens, and the VA refused to help pay for the removal of dust-trapping carpets, he said.

Thompson’s presence at the hearing, though, was not just meant to put the spotlight on the VA. The military’s entire approach to toxic exposure is a morass that leaves ill soldiers and veterans like Thompson trying to navigate a bureaucracy more labyrinthine than the Pentagon’s corridors.

After Thompson was shipped back to Fort Stewart in Georgia, his medical ordeal was at first addressed within the military system, including a year at Walter Reed National Military Medical Center in Bethesda, Maryland, where doctors found his lungs filled with titanium, magnesium, iron and silica.

Yet he said he didn’t qualify for the Army’s traumatic-injury insurance program, which might have helped him pay to retrofit his home in West Virginia. And he can’t get his military retirement pay until he’s 60.

“I may not live to be age 60. I turn 50 this year,” Thompson said.

Illustrating the problem, several officials at the hearing with the Department of Defense, the Army and the National Guard were unable to explain why Thompson — with 23 years of service between the Guard and Army — might have such a hard time qualifying for retirement benefits when the evidence of his lungs and the findings of the Army’s own doctors are so vivid and extreme.

For advocates who have been working on the problem for decades, it reminds them all too vividly of Agent Orange, which the military is still coming to grips with.

“It’s already been, since the first Persian Gulf [War] — we’re talking 30 years — and since burn pits were again active, since 2001,” said Liermann. “We’re way behind the curve here.”

Although Congress has done relatively little to deal with burn pits, many members seem to at least be thinking along the same lines. The Senate Veterans’ Affairs hearing promised to be something of a kickoff to a year when lawmakers are poised to offer a slew of bills designed to confront the military’s inability to care for service members poisoned during their deployments.

“Make no mistake about it,” said the committee chairman, Sen. Jon Tester (D-Mont.). “We hold these hearings for two reasons: to gather information for the committee members and to help educate the VA that they might take action before Congress does.”

Republicans have also shown growing interest in the problem, offering targeted bills to ensure a handful of toxin-related diseases are covered by the VA.

At the hearing, conservative freshman Sen. Tommy Tuberville (R-Ala.) seemed especially moved.

“We got to do a better job of taking care of our young people,” Tuberville said. “If we’re going to go to war, we got to understand we got to pay the price for it on both ends.”

There is also likely to be high-profile support and attention when revised legislation starts rolling out this spring.

The broadest bill likely to be offered was first introduced by Sen. Kirsten Gillibrand (D-N.Y.) in the Senate and Rep. Raul Ruiz (D-Calif.) in the House in late 2019, with a boost from former “Daily Show” host Jon Stewart and a cadre of 9/11 responders who are turning their attention to toxic exposures.

Indeed, Ruiz and Gillibrand’s legislation is modeled in part on the 9/11 health act that passed in 2015. The burn pit bill would remove the burden of proving a service-related connection.

It would vastly simplify the lives of people like Thompson.

“I am a warrior of the United States of America. I gave my lungs for my country,” Thompson said.

He was cut off before he could finish, but his prepared remarks concluded, “Hopefully, after hearing my story, it will bring awareness for not only me but others who are battling the same or similar injuries related to burn pit exposures from Iraq or Afghanistan.”

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

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The lungs Bill Thompson was born with told a gruesome, harrowing and unmistakable tale to Dr. Anthony Szema when he analyzed them and found the black spots, scarring, partially combusted jet fuel and metal inside.

The retired Army staff sergeant had suffered catastrophic lung damage from breathing incinerated waste burned in massive open-air pits and probably other irritants during his tour of duty in Iraq.

“There’s black spots that are burns, particles all over; there’s metal. It was all scarred,” said Szema, a pulmonologist and professor who studies toxic exposures and examined Thompson’s preserved lung tissue. “There was no gas exchange anywhere in that lung.”

Thompson is still alive, surviving on his second transplanted set of lungs. Yet the story burned into the veteran’s internal organs is not one that has been entirely convincing to the U.S. government.

The military has not linked the burn pits to illness. That means many who were exposed to burn pits and are sick do not qualify for benefits under any existing program.

Retirement and health benefits for members of the military depend on factors like length of service, active or reserve status, deployments to combat zones and whether the military considers specific injuries or illnesses to be service-related. Thompson has been able to get care through the Department of Veterans Affairs for his lung disease but has not been able to secure other benefits, like early retirement pay.

“I was denied my Army retirement because if it was not a combat action, then I don’t receive that retirement,” Thompson said at a Senate Veterans’ Affairs Committee hearing last week on service members’ exposures to toxic substances.

Thompson is one of at least 3.5 million veterans since 2001 who have served in war zones where the U.S. military decided to dispose of its trash by burning it, according to VA estimates.

It’s not clear how many people within that population have gotten sick from exposure. Only a small fraction — 234,000 — have enrolled in the VA’s online burn pit registry. Veterans’ advocacy groups have said the majority of claims to the agency stemming from toxic exposures are denied, even as most former service members report contacts with toxins in their deployments.

Soldiers returning from tours in the global war on terror have reported debilitating illnesses almost from its beginning, but got little traction with the military. This year, though, the likelihood of congressional action is high, with Democrats expressing interest and a president who suspects burn pits are to blame for his son’s death.

President Joe Biden’s son Beau died of brain cancer in 2015 at age 46. He had deployed to Iraq in two sites with burn pits — at Baghdad and Balad — around the same time Thompson was at Camp Striker, near the Baghdad airport.

“Because of exposure to burn pits — in my view, I can’t prove it yet — he came back with stage 4 glioblastoma,” Biden said in a 2019 speech.

In testimony at the March 10 hearing, Shane Liermann, who works for the group Disabled American Veterans, told the committee that 78% of burn pit claims are denied. “Part of the problem is VA is not recognizing that exposure as being toxic exposures,” Liermann said.

Aleks Morosky, with the Wounded Warrior Project, said that in his group’s survey of 28,000 veterans last year, 71% said they had “definitely” been exposed to toxic substances or hazardous chemicals, and 18% said they had “probably” been exposed. Half of those people rated their health as poor or fair. Only about 16% of the service members who believed they had suffered exposure said they got treatment from the VA, and 11% said they were denied treatment.

Thompson, who is 49, said care for his lung disease is often slow and sometimes denied. It took the VA three years to approve an air purifier for his home to filter out allergens, and the VA refused to help pay for the removal of dust-trapping carpets, he said.

Thompson’s presence at the hearing, though, was not just meant to put the spotlight on the VA. The military’s entire approach to toxic exposure is a morass that leaves ill soldiers and veterans like Thompson trying to navigate a bureaucracy more labyrinthine than the Pentagon’s corridors.

After Thompson was shipped back to Fort Stewart in Georgia, his medical ordeal was at first addressed within the military system, including a year at Walter Reed National Military Medical Center in Bethesda, Maryland, where doctors found his lungs filled with titanium, magnesium, iron and silica.

Yet he said he didn’t qualify for the Army’s traumatic-injury insurance program, which might have helped him pay to retrofit his home in West Virginia. And he can’t get his military retirement pay until he’s 60.

“I may not live to be age 60. I turn 50 this year,” Thompson said.

Illustrating the problem, several officials at the hearing with the Department of Defense, the Army and the National Guard were unable to explain why Thompson — with 23 years of service between the Guard and Army — might have such a hard time qualifying for retirement benefits when the evidence of his lungs and the findings of the Army’s own doctors are so vivid and extreme.

For advocates who have been working on the problem for decades, it reminds them all too vividly of Agent Orange, which the military is still coming to grips with.

“It’s already been, since the first Persian Gulf [War] — we’re talking 30 years — and since burn pits were again active, since 2001,” said Liermann. “We’re way behind the curve here.”

Although Congress has done relatively little to deal with burn pits, many members seem to at least be thinking along the same lines. The Senate Veterans’ Affairs hearing promised to be something of a kickoff to a year when lawmakers are poised to offer a slew of bills designed to confront the military’s inability to care for service members poisoned during their deployments.

“Make no mistake about it,” said the committee chairman, Sen. Jon Tester (D-Mont.). “We hold these hearings for two reasons: to gather information for the committee members and to help educate the VA that they might take action before Congress does.”

Republicans have also shown growing interest in the problem, offering targeted bills to ensure a handful of toxin-related diseases are covered by the VA.

At the hearing, conservative freshman Sen. Tommy Tuberville (R-Ala.) seemed especially moved.

“We got to do a better job of taking care of our young people,” Tuberville said. “If we’re going to go to war, we got to understand we got to pay the price for it on both ends.”

There is also likely to be high-profile support and attention when revised legislation starts rolling out this spring.

The broadest bill likely to be offered was first introduced by Sen. Kirsten Gillibrand (D-N.Y.) in the Senate and Rep. Raul Ruiz (D-Calif.) in the House in late 2019, with a boost from former “Daily Show” host Jon Stewart and a cadre of 9/11 responders who are turning their attention to toxic exposures.

Indeed, Ruiz and Gillibrand’s legislation is modeled in part on the 9/11 health act that passed in 2015. The burn pit bill would remove the burden of proving a service-related connection.

It would vastly simplify the lives of people like Thompson.

“I am a warrior of the United States of America. I gave my lungs for my country,” Thompson said.

He was cut off before he could finish, but his prepared remarks concluded, “Hopefully, after hearing my story, it will bring awareness for not only me but others who are battling the same or similar injuries related to burn pit exposures from Iraq or Afghanistan.”

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

USE OUR CONTENT

This story can be republished for free (details).

Subscribe to KHN's free Morning Briefing.

The lungs Bill Thompson was born with told a gruesome, harrowing and unmistakable tale to Dr. Anthony Szema when he analyzed them and found the black spots, scarring, partially combusted jet fuel and metal inside.

The retired Army staff sergeant had suffered catastrophic lung damage from breathing incinerated waste burned in massive open-air pits and probably other irritants during his tour of duty in Iraq.

“There’s black spots that are burns, particles all over; there’s metal. It was all scarred,” said Szema, a pulmonologist and professor who studies toxic exposures and examined Thompson’s preserved lung tissue. “There was no gas exchange anywhere in that lung.”

Thompson is still alive, surviving on his second transplanted set of lungs. Yet the story burned into the veteran’s internal organs is not one that has been entirely convincing to the U.S. government.

The military has not linked the burn pits to illness. That means many who were exposed to burn pits and are sick do not qualify for benefits under any existing program.

Retirement and health benefits for members of the military depend on factors like length of service, active or reserve status, deployments to combat zones and whether the military considers specific injuries or illnesses to be service-related. Thompson has been able to get care through the Department of Veterans Affairs for his lung disease but has not been able to secure other benefits, like early retirement pay.

“I was denied my Army retirement because if it was not a combat action, then I don’t receive that retirement,” Thompson said at a Senate Veterans’ Affairs Committee hearing last week on service members’ exposures to toxic substances.

Thompson is one of at least 3.5 million veterans since 2001 who have served in war zones where the U.S. military decided to dispose of its trash by burning it, according to VA estimates.

It’s not clear how many people within that population have gotten sick from exposure. Only a small fraction — 234,000 — have enrolled in the VA’s online burn pit registry. Veterans’ advocacy groups have said the majority of claims to the agency stemming from toxic exposures are denied, even as most former service members report contacts with toxins in their deployments.

Soldiers returning from tours in the global war on terror have reported debilitating illnesses almost from its beginning, but got little traction with the military. This year, though, the likelihood of congressional action is high, with Democrats expressing interest and a president who suspects burn pits are to blame for his son’s death.

President Joe Biden’s son Beau died of brain cancer in 2015 at age 46. He had deployed to Iraq in two sites with burn pits — at Baghdad and Balad — around the same time Thompson was at Camp Striker, near the Baghdad airport.

“Because of exposure to burn pits — in my view, I can’t prove it yet — he came back with stage 4 glioblastoma,” Biden said in a 2019 speech.

In testimony at the March 10 hearing, Shane Liermann, who works for the group Disabled American Veterans, told the committee that 78% of burn pit claims are denied. “Part of the problem is VA is not recognizing that exposure as being toxic exposures,” Liermann said.

Aleks Morosky, with the Wounded Warrior Project, said that in his group’s survey of 28,000 veterans last year, 71% said they had “definitely” been exposed to toxic substances or hazardous chemicals, and 18% said they had “probably” been exposed. Half of those people rated their health as poor or fair. Only about 16% of the service members who believed they had suffered exposure said they got treatment from the VA, and 11% said they were denied treatment.

Thompson, who is 49, said care for his lung disease is often slow and sometimes denied. It took the VA three years to approve an air purifier for his home to filter out allergens, and the VA refused to help pay for the removal of dust-trapping carpets, he said.

Thompson’s presence at the hearing, though, was not just meant to put the spotlight on the VA. The military’s entire approach to toxic exposure is a morass that leaves ill soldiers and veterans like Thompson trying to navigate a bureaucracy more labyrinthine than the Pentagon’s corridors.

After Thompson was shipped back to Fort Stewart in Georgia, his medical ordeal was at first addressed within the military system, including a year at Walter Reed National Military Medical Center in Bethesda, Maryland, where doctors found his lungs filled with titanium, magnesium, iron and silica.

Yet he said he didn’t qualify for the Army’s traumatic-injury insurance program, which might have helped him pay to retrofit his home in West Virginia. And he can’t get his military retirement pay until he’s 60.

“I may not live to be age 60. I turn 50 this year,” Thompson said.

Illustrating the problem, several officials at the hearing with the Department of Defense, the Army and the National Guard were unable to explain why Thompson — with 23 years of service between the Guard and Army — might have such a hard time qualifying for retirement benefits when the evidence of his lungs and the findings of the Army’s own doctors are so vivid and extreme.

For advocates who have been working on the problem for decades, it reminds them all too vividly of Agent Orange, which the military is still coming to grips with.

“It’s already been, since the first Persian Gulf [War] — we’re talking 30 years — and since burn pits were again active, since 2001,” said Liermann. “We’re way behind the curve here.”

Although Congress has done relatively little to deal with burn pits, many members seem to at least be thinking along the same lines. The Senate Veterans’ Affairs hearing promised to be something of a kickoff to a year when lawmakers are poised to offer a slew of bills designed to confront the military’s inability to care for service members poisoned during their deployments.

“Make no mistake about it,” said the committee chairman, Sen. Jon Tester (D-Mont.). “We hold these hearings for two reasons: to gather information for the committee members and to help educate the VA that they might take action before Congress does.”

Republicans have also shown growing interest in the problem, offering targeted bills to ensure a handful of toxin-related diseases are covered by the VA.

At the hearing, conservative freshman Sen. Tommy Tuberville (R-Ala.) seemed especially moved.

“We got to do a better job of taking care of our young people,” Tuberville said. “If we’re going to go to war, we got to understand we got to pay the price for it on both ends.”

There is also likely to be high-profile support and attention when revised legislation starts rolling out this spring.

The broadest bill likely to be offered was first introduced by Sen. Kirsten Gillibrand (D-N.Y.) in the Senate and Rep. Raul Ruiz (D-Calif.) in the House in late 2019, with a boost from former “Daily Show” host Jon Stewart and a cadre of 9/11 responders who are turning their attention to toxic exposures.

Indeed, Ruiz and Gillibrand’s legislation is modeled in part on the 9/11 health act that passed in 2015. The burn pit bill would remove the burden of proving a service-related connection.

It would vastly simplify the lives of people like Thompson.

“I am a warrior of the United States of America. I gave my lungs for my country,” Thompson said.

He was cut off before he could finish, but his prepared remarks concluded, “Hopefully, after hearing my story, it will bring awareness for not only me but others who are battling the same or similar injuries related to burn pit exposures from Iraq or Afghanistan.”

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

USE OUR CONTENT

This story can be republished for free (details).

Subscribe to KHN's free Morning Briefing.

The first large study of its kind reveals that SARS-CoV-2 reinfections remain rare, although people older than 65 are at higher risk.

When researchers analyzed test results of 4 million people in Denmark, they found that less than 1% of those who tested positive experienced reinfection.

Initial infection was associated with about 80% protection overall against getting SARS-CoV-2 again. However, among those older than 65, the protection plummeted to 47%.

“Not everybody is protected against reinfection after a first infection. Older people are at higher risk of catching it again,” co–lead author Daniela Michlmayr, PhD, said in an interview. “Our findings emphasize the importance of policies to protect the elderly and of adhering to infection control measures and restrictions, even if previously infected with COVID-19.”
 

Verifying the need for vaccination

“The findings also highlight the need to vaccinate people who had COVID-19 before, as natural immunity to infection – especially among the elderly 65 and older – cannot be relied upon,” added Dr. Michlmayr, a researcher in the department of bacteria, parasites, and fungi at the Staten Serums Institut, Copenhagen.

The population-based observational study was published online March 17 in The Lancet.

“The findings make sense, as patients who are immunocompromised or of advanced age may not mount an immune response that is as long-lasting,” David Hirschwerk, MD, said in an interview. “It does underscore the importance of vaccination for people of more advanced age, even if they previously were infected with COVID.

“For those who were infected last spring and have not yet been vaccinated, this helps to support the value of still pursuing the vaccine,” added Dr. Hirschwerk, an infectious disease specialist at Northwell Health in Manhasset, N.Y.

Evidence on reinfection risk was limited prior to this study. “Little is known about protection against SARS-CoV-2 repeat infections, but two studies in the UK have found that immunity could last at least 5 to 6 months after infection,” the authors noted.

Along with co–lead author Christian Holm Hansen, PhD, Dr. Michlmayr and colleagues found that 2.11% of 525,339 individuals tested positive for SARS-CoV-2 during the first surge in Denmark from March to May 2020. Within this group, 0.65% tested positive during a second surge from September to December.

By the end of 2020, more than 10 million people had undergone free polymerase chain reaction testing by the Danish government or through the national TestDenmark program.

“My overall take is that it is great to have such a big dataset looking at this question,” E. John Wherry, PhD, said in an interview. The findings support “what we’ve seen in previous, smaller studies.”

Natural protection against reinfection of approximately 80% “is not as good as the vaccines, but not bad,” added Dr. Wherry, director of the Institute for Immunology at the University of Pennsylvania, Philadelphia.
 

Age alters immunity?

“Our finding that older people were more likely than younger people to test positive again if they had already tested positive could be explained by natural age-related changes in the immune system of older adults, also referred to as immune senescence,” the authors noted.

The investigators found no significant differences in reinfection rates between women and men.

As with the previous research, this study also indicates that an initial bout with SARS-CoV-2 infection appears to confer protection for at least 6 months. The researchers found no significant differences between people who were followed for 3-6 months and those followed for 7 months or longer.
 

Variants not included

To account for possible bias among people who got tested repeatedly, Dr. Michlmayr and colleagues performed a sensitivity analysis in a subgroup. They assessed reinfection rates among people who underwent testing frequently and routinely – nurses, doctors, social workers, and health care assistants – and found that 1.2% tested positive a second time during the second surge.

A limitation of the study was the inability to correlate symptoms with risk for reinfection. Also, the researchers did not account for SARS-CoV-2 variants, noting that “during the study period, such variants were not yet established in Denmark; although into 2021 this pattern is changing.”

Asked to speculate whether the results would be different had the study accounted for variants, Dr. Hirschwerk said, “It depends upon the variant, but certainly for the B.1.351 variant, there already has been data clearly demonstrating risk of reinfection with SARS-CoV-2 despite prior infection with the original strain of virus.”

The emergence of SARS-CoV-2 variants of concern that could escape natural and vaccine-related immunity “complicates matters further,” Rosemary J. Boyton, MBBS, and Daniel M. Altmann, PhD, both of Imperial College London, wrote in an accompanying comment in The Lancet.

“Emerging variants of concern might shift immunity below a protective margin, prompting the need for updated vaccines. Interestingly, vaccine responses even after single dose are substantially enhanced in individuals with a history of infection with SARS-CoV-2,” they added.

The current study confirms that “the hope of protective immunity through natural infections might not be within our reach, and a global vaccination program with high efficacy vaccines is the enduring solution,” Dr. Boyton and Dr. Altmann noted.

Cause for alarm?

Despite evidence that reinfection is relatively rare, “many will find the data reported by Hansen and colleagues about protection through natural infection relatively alarming,” Dr. Boyton and Dr. Altmann wrote in their commentary. The 80% protection rate from reinfection in general and the 47% rate among people aged 65 and older “are more concerning figures than offered by previous studies.”

Vaccines appear to provide better quality, quantity, and durability of protection against repeated infection – measured in terms of neutralizing antibodies and T cells – compared with previous infection with SARS-CoV-2, Dr. Boyton and Dr. Altmann wrote.
 

More research needed

The duration of natural protection against reinfection remains an unanswered question, the researchers noted, “because too little time has elapsed since the beginning of the pandemic.”

Future prospective and longitudinal cohort studies coupled with molecular surveillance are needed to characterize antibody titers and waning of protection against repeat infections, the authors noted. Furthermore, more answers are needed regarding how some virus variants might contribute to reinfection risk.

No funding for the study has been reported. Dr. Michlmayr, Dr. Hirschwerk, Dr. Wherry, Dr. Boyton, and Dr. Altmann have disclosed no relevant financial relationships.
 

A version of this article first appeared on Medscape.com.

The first large study of its kind reveals that SARS-CoV-2 reinfections remain rare, although people older than 65 are at higher risk.

When researchers analyzed test results of 4 million people in Denmark, they found that less than 1% of those who tested positive experienced reinfection.

Initial infection was associated with about 80% protection overall against getting SARS-CoV-2 again. However, among those older than 65, the protection plummeted to 47%.

“Not everybody is protected against reinfection after a first infection. Older people are at higher risk of catching it again,” co–lead author Daniela Michlmayr, PhD, said in an interview. “Our findings emphasize the importance of policies to protect the elderly and of adhering to infection control measures and restrictions, even if previously infected with COVID-19.”
 

Verifying the need for vaccination

“The findings also highlight the need to vaccinate people who had COVID-19 before, as natural immunity to infection – especially among the elderly 65 and older – cannot be relied upon,” added Dr. Michlmayr, a researcher in the department of bacteria, parasites, and fungi at the Staten Serums Institut, Copenhagen.

The population-based observational study was published online March 17 in The Lancet.

“The findings make sense, as patients who are immunocompromised or of advanced age may not mount an immune response that is as long-lasting,” David Hirschwerk, MD, said in an interview. “It does underscore the importance of vaccination for people of more advanced age, even if they previously were infected with COVID.

“For those who were infected last spring and have not yet been vaccinated, this helps to support the value of still pursuing the vaccine,” added Dr. Hirschwerk, an infectious disease specialist at Northwell Health in Manhasset, N.Y.

Evidence on reinfection risk was limited prior to this study. “Little is known about protection against SARS-CoV-2 repeat infections, but two studies in the UK have found that immunity could last at least 5 to 6 months after infection,” the authors noted.

Along with co–lead author Christian Holm Hansen, PhD, Dr. Michlmayr and colleagues found that 2.11% of 525,339 individuals tested positive for SARS-CoV-2 during the first surge in Denmark from March to May 2020. Within this group, 0.65% tested positive during a second surge from September to December.

By the end of 2020, more than 10 million people had undergone free polymerase chain reaction testing by the Danish government or through the national TestDenmark program.

“My overall take is that it is great to have such a big dataset looking at this question,” E. John Wherry, PhD, said in an interview. The findings support “what we’ve seen in previous, smaller studies.”

Natural protection against reinfection of approximately 80% “is not as good as the vaccines, but not bad,” added Dr. Wherry, director of the Institute for Immunology at the University of Pennsylvania, Philadelphia.
 

Age alters immunity?

“Our finding that older people were more likely than younger people to test positive again if they had already tested positive could be explained by natural age-related changes in the immune system of older adults, also referred to as immune senescence,” the authors noted.

The investigators found no significant differences in reinfection rates between women and men.

As with the previous research, this study also indicates that an initial bout with SARS-CoV-2 infection appears to confer protection for at least 6 months. The researchers found no significant differences between people who were followed for 3-6 months and those followed for 7 months or longer.
 

Variants not included

To account for possible bias among people who got tested repeatedly, Dr. Michlmayr and colleagues performed a sensitivity analysis in a subgroup. They assessed reinfection rates among people who underwent testing frequently and routinely – nurses, doctors, social workers, and health care assistants – and found that 1.2% tested positive a second time during the second surge.

A limitation of the study was the inability to correlate symptoms with risk for reinfection. Also, the researchers did not account for SARS-CoV-2 variants, noting that “during the study period, such variants were not yet established in Denmark; although into 2021 this pattern is changing.”

Asked to speculate whether the results would be different had the study accounted for variants, Dr. Hirschwerk said, “It depends upon the variant, but certainly for the B.1.351 variant, there already has been data clearly demonstrating risk of reinfection with SARS-CoV-2 despite prior infection with the original strain of virus.”

The emergence of SARS-CoV-2 variants of concern that could escape natural and vaccine-related immunity “complicates matters further,” Rosemary J. Boyton, MBBS, and Daniel M. Altmann, PhD, both of Imperial College London, wrote in an accompanying comment in The Lancet.

“Emerging variants of concern might shift immunity below a protective margin, prompting the need for updated vaccines. Interestingly, vaccine responses even after single dose are substantially enhanced in individuals with a history of infection with SARS-CoV-2,” they added.

The current study confirms that “the hope of protective immunity through natural infections might not be within our reach, and a global vaccination program with high efficacy vaccines is the enduring solution,” Dr. Boyton and Dr. Altmann noted.

Cause for alarm?

Despite evidence that reinfection is relatively rare, “many will find the data reported by Hansen and colleagues about protection through natural infection relatively alarming,” Dr. Boyton and Dr. Altmann wrote in their commentary. The 80% protection rate from reinfection in general and the 47% rate among people aged 65 and older “are more concerning figures than offered by previous studies.”

Vaccines appear to provide better quality, quantity, and durability of protection against repeated infection – measured in terms of neutralizing antibodies and T cells – compared with previous infection with SARS-CoV-2, Dr. Boyton and Dr. Altmann wrote.
 

More research needed

The duration of natural protection against reinfection remains an unanswered question, the researchers noted, “because too little time has elapsed since the beginning of the pandemic.”

Future prospective and longitudinal cohort studies coupled with molecular surveillance are needed to characterize antibody titers and waning of protection against repeat infections, the authors noted. Furthermore, more answers are needed regarding how some virus variants might contribute to reinfection risk.

No funding for the study has been reported. Dr. Michlmayr, Dr. Hirschwerk, Dr. Wherry, Dr. Boyton, and Dr. Altmann have disclosed no relevant financial relationships.
 

A version of this article first appeared on Medscape.com.

The first large study of its kind reveals that SARS-CoV-2 reinfections remain rare, although people older than 65 are at higher risk.

When researchers analyzed test results of 4 million people in Denmark, they found that less than 1% of those who tested positive experienced reinfection.

Initial infection was associated with about 80% protection overall against getting SARS-CoV-2 again. However, among those older than 65, the protection plummeted to 47%.

“Not everybody is protected against reinfection after a first infection. Older people are at higher risk of catching it again,” co–lead author Daniela Michlmayr, PhD, said in an interview. “Our findings emphasize the importance of policies to protect the elderly and of adhering to infection control measures and restrictions, even if previously infected with COVID-19.”
 

Verifying the need for vaccination

“The findings also highlight the need to vaccinate people who had COVID-19 before, as natural immunity to infection – especially among the elderly 65 and older – cannot be relied upon,” added Dr. Michlmayr, a researcher in the department of bacteria, parasites, and fungi at the Staten Serums Institut, Copenhagen.

The population-based observational study was published online March 17 in The Lancet.

“The findings make sense, as patients who are immunocompromised or of advanced age may not mount an immune response that is as long-lasting,” David Hirschwerk, MD, said in an interview. “It does underscore the importance of vaccination for people of more advanced age, even if they previously were infected with COVID.

“For those who were infected last spring and have not yet been vaccinated, this helps to support the value of still pursuing the vaccine,” added Dr. Hirschwerk, an infectious disease specialist at Northwell Health in Manhasset, N.Y.

Evidence on reinfection risk was limited prior to this study. “Little is known about protection against SARS-CoV-2 repeat infections, but two studies in the UK have found that immunity could last at least 5 to 6 months after infection,” the authors noted.

Along with co–lead author Christian Holm Hansen, PhD, Dr. Michlmayr and colleagues found that 2.11% of 525,339 individuals tested positive for SARS-CoV-2 during the first surge in Denmark from March to May 2020. Within this group, 0.65% tested positive during a second surge from September to December.

By the end of 2020, more than 10 million people had undergone free polymerase chain reaction testing by the Danish government or through the national TestDenmark program.

“My overall take is that it is great to have such a big dataset looking at this question,” E. John Wherry, PhD, said in an interview. The findings support “what we’ve seen in previous, smaller studies.”

Natural protection against reinfection of approximately 80% “is not as good as the vaccines, but not bad,” added Dr. Wherry, director of the Institute for Immunology at the University of Pennsylvania, Philadelphia.
 

Age alters immunity?

“Our finding that older people were more likely than younger people to test positive again if they had already tested positive could be explained by natural age-related changes in the immune system of older adults, also referred to as immune senescence,” the authors noted.

The investigators found no significant differences in reinfection rates between women and men.

As with the previous research, this study also indicates that an initial bout with SARS-CoV-2 infection appears to confer protection for at least 6 months. The researchers found no significant differences between people who were followed for 3-6 months and those followed for 7 months or longer.
 

Variants not included

To account for possible bias among people who got tested repeatedly, Dr. Michlmayr and colleagues performed a sensitivity analysis in a subgroup. They assessed reinfection rates among people who underwent testing frequently and routinely – nurses, doctors, social workers, and health care assistants – and found that 1.2% tested positive a second time during the second surge.

A limitation of the study was the inability to correlate symptoms with risk for reinfection. Also, the researchers did not account for SARS-CoV-2 variants, noting that “during the study period, such variants were not yet established in Denmark; although into 2021 this pattern is changing.”

Asked to speculate whether the results would be different had the study accounted for variants, Dr. Hirschwerk said, “It depends upon the variant, but certainly for the B.1.351 variant, there already has been data clearly demonstrating risk of reinfection with SARS-CoV-2 despite prior infection with the original strain of virus.”

The emergence of SARS-CoV-2 variants of concern that could escape natural and vaccine-related immunity “complicates matters further,” Rosemary J. Boyton, MBBS, and Daniel M. Altmann, PhD, both of Imperial College London, wrote in an accompanying comment in The Lancet.

“Emerging variants of concern might shift immunity below a protective margin, prompting the need for updated vaccines. Interestingly, vaccine responses even after single dose are substantially enhanced in individuals with a history of infection with SARS-CoV-2,” they added.

The current study confirms that “the hope of protective immunity through natural infections might not be within our reach, and a global vaccination program with high efficacy vaccines is the enduring solution,” Dr. Boyton and Dr. Altmann noted.

Cause for alarm?

Despite evidence that reinfection is relatively rare, “many will find the data reported by Hansen and colleagues about protection through natural infection relatively alarming,” Dr. Boyton and Dr. Altmann wrote in their commentary. The 80% protection rate from reinfection in general and the 47% rate among people aged 65 and older “are more concerning figures than offered by previous studies.”

Vaccines appear to provide better quality, quantity, and durability of protection against repeated infection – measured in terms of neutralizing antibodies and T cells – compared with previous infection with SARS-CoV-2, Dr. Boyton and Dr. Altmann wrote.
 

More research needed

The duration of natural protection against reinfection remains an unanswered question, the researchers noted, “because too little time has elapsed since the beginning of the pandemic.”

Future prospective and longitudinal cohort studies coupled with molecular surveillance are needed to characterize antibody titers and waning of protection against repeat infections, the authors noted. Furthermore, more answers are needed regarding how some virus variants might contribute to reinfection risk.

No funding for the study has been reported. Dr. Michlmayr, Dr. Hirschwerk, Dr. Wherry, Dr. Boyton, and Dr. Altmann have disclosed no relevant financial relationships.
 

A version of this article first appeared on Medscape.com.

Buprenorphine for the treatment of opioid-use disorder (OUD) may also mitigate the risk associated with concomitant benzodiazepine and Z-drug use, which is frequent in this patient population, new research suggests.

A case-crossover study of more than 20,000 participants with OUD showed that drug treatment days in which benzodiazepines and Z-drugs were taken were associated with an 88% increase in nonfatal overdose; buprenorphine appeared to reduce this risk by almost 40%.

“One of our two primary findings is that patients with opioid use disorder can still benefit substantially from buprenorphine treatment, even if they have benzodiazepines on board,” lead author Kevin Xu, MD, a resident at the Washington University, St. Louis, told this news organization.

The other key finding was that “not all benzodiazepines are equal” and that some are associated with higher risk than others, Dr. Xu added.

“If anything, patients who are on buprenorphine and benzodiazepines do not necessarily need to be abruptly tapered off their benzodiazepines. Our data actually demonstrate that there are safe avenues for them,” he added.

The findings were published online March 3 in the American Journal of Psychiatry.
 

Cloudy relationship

Buprenorphine is commonly used to treat patients with OUD because of its ability to decrease all-cause mortality. However, up to 30% of these patients also take benzodiazepines for comorbid mood and anxiety disorders, Dr. Xu noted.

In addition, recent research shows that benzodiazepine/Z-drug use is associated with a variety of potential adverse effects, including respiratory depression, overdose, and addiction risk.

The relationship between benzodiazepine use and buprenorphine treatment outcomes is poorly characterized in individuals with OUD. Although some studies suggest benzodiazepines may enhance retention in buprenorphine maintenance treatment, others suggest a link to increased adverse events, including all-cause mortality, drug-related poisonings, and accidental injury–related emergency department visits.

In addition, there has been little research on the potential adverse effects associated with use of selective benzodiazepine receptor modulators in patients with OUD. These so-called Z-drugs include zolpidem, zaleplon, and eszopiclone.

Nevertheless, previous research in the general population shows that these medications have a range of adverse effects similar to those of benzodiazepines, with comparable dose-response effects on all-cause mortality.

“The challenge for any clinician is that many patients who are addicted to opioids are also polysubstance users,” said Dr. Xu. “There are so many hopeful articles regarding the benefits of buprenorphine treatment in opioid use disorder patients, but it seems like the individuals with polysubstance use are largely ignored in the setting of the opioid epidemic.”

“And this is really the back story that got me inspired to study this particular topic,” he added.
 

Improve, nullify, or reverse?

Given these questions, the researchers set out to quantify the odds of nonfatal drug-related poisoning, including overdoses, associated with benzodiazepine or Z-drug use by patients with OUD who were also taking buprenorphine.

“While the drug-related poisoning variable encompasses opioid overdoses, we used a broad definition per CDC guidelines to also include other types of drug overdoses – including poisoning events involving stimulants, overdoses involving sedatives, and overdoses involving psychotropic prescription drugs” that are commonly used by patients with OUD, said Dr. Xu.

They also wanted to determine whether the use of benzodiazepines or Z-drugs would improve, nullify, or reverse the protective effect of buprenorphine. The researchers also evaluated whether different sedative and hypnotic subtypes of these drugs were associated with different poisoning risks.

The researchers analyzed pharmaceutical claims data from 304,676 individuals (aged 12-64 years) in the IBM MarketScan Commercial and Multi-State Medicaid Databases. All had received buprenorphine treatment for OUD between Jan. 1, 2006, and Dec. 31, 2016.

Buprenorphine use was converted to a daily milligram dose and was classified as either greater than 12 mg or less than or equal to 12 mg, because previous research suggests there may be differences in treatment retention associated with this dose. Given the case-control nature of the investigation, patients who did not experience a drug-related poisoning were excluded from the analysis.

The study’s primary unit of observation was person-days, which were those days during which patients were enrolled in a health insurance plan. Participants were evaluated for 1 year before their first drug-related poisoning and 1 year after their first such poisoning. The primary outcome was nonfatal drug-related poisonings, including overdoses. The primary exposure was determined on the basis of benzodiazepine or Z-drug prescriptions.

The daily dose of benzodiazepines or Z-drugs was standardized as a function of diazepam-equivalent milligrams. Doses were classified as either high dose (diazepam-equivalent mg dose >30 mg) or low dose (≤30 mg). The drugs were also distinguished on the basis of their pharmacologic properties, such as whether they were short-acting or long-acting.
 

37% risk reduction

Of the original cohort of 304,676 patients with OUD, the study’s final analytic sample included 23,036 patients (mean age, 30 years; 51% men), representing 14,213,075 person-days of insurance coverage. Of these, 2,210,927 person-days (15.6%) entailed claims for buprenorphine (mean daily dose, 15.4 mg; SD, 7.31 mg).

A total of 474,181 person-days included claims for benzodiazepines or Z-drugs with concurrent buprenorphine treatment. The mean daily dose of any benzodiazepine or Z-drug was 23.4 diazepam-milligram equivalents. The mean daily dose of short-acting benzodiazepines, long-acting benzodiazepines, and Z-drugs was 25.3, 31.3, and 4.9 diazepam-milligram equivalents, respectively.

Buprenorphine treatment days were associated with a 37% lower chance of drug-related poisoning (95% confidence interval, 0.60-0.66) in comparison with nontreatment days. On the other hand, the odds of poisoning increased by 81% on days on which patients were treated with Z-drugs or benzodiazepines (95% CI, 1.73-1.91).

Interestingly, individual analyses showed that benzodiazepine and Z-drug treatment days were associated with increased odds of poisoning events (odds ratio, 1.29; 95% CI, 1.19-1.39). Odds of poisoning events on benzodiazepine-only treatment days, on the other hand, were markedly lower (OR, 1.88; 95% CI, 1.78-1.98).

Subgroup analyses revealed that both short-acting and long-acting benzodiazepine treatment days were associated with comparably elevated odds of drug-related poisoning (OR, 1.86 and 1.68, respectively). High-dose benzodiazepine treatment days were associated with higher increased odds of a poisoning event (122%) in comparison with low-dose treatment days (78%).

High-dose, but not low-dose, benzodiazepine or Z-drug treatment was linked to increased poisonings when the drug was taken concurrently with buprenorphine (OR, 1.64; 95% CI, 1.39-1.93). However, the risk was still lower than the risk associated with taking the agents without concurrent treatment with buprenorphine (low-dose OR, 1.69; high-dose OR, 2.23).
 

‘Not all benzodiazepines are bad’

Dr. Xu noted that the findings have potentially important implications for clinical practice, beginning with the dose-dependent relationship between benzodiazepine/Z-drug use and drug-related poisonings among individuals with OUD. This indicates that lowering doses or shortening treatment duration may reduce risk, he said.

Similarly, the lower risk associated with long-acting benzodiazepines relative to short-acting beonzodiazepines – as well as the substantially lower risk associated with Z-drugs, compared with either short- or long-acting benzodiazepines – suggests that switching from benzodiazepines to long-acting agents or Z-drugs may lower the risk for overdose, he added.

“Clinicians are often challenged by patients with opioid use disorder who are also on benzodiazepines or Z-drugs. There’s an inclination to say no to them, because they’re too high risk to start buprenorphine maintenance, or abruptly taper the benzodiazepines, which can be very destabilizing,” he noted.

“Our data show that people on benzodiazepines can absolutely receive buprenorphine and still get some benefit,” Dr. Xu said. “In addition, not all benzodiazepines are bad for these individuals. There are safer formulations and safer doses, too.”

However, he added, he would not initiate benzodiazepine treatment if he didn’t have to, especially long-term treatment.

“One of the messages from our data is that this clearly contributes to higher overdose risk. But we often inherit patients who already have benzodiazepines on board, so we need to figure out what to do. That is the question that nobody had really clearly addressed prior to this study,” Dr. Xu concluded.
 

Vigilance needed

Commenting on the findings for this news organization, Jerrold F. Rosenbaum, MD, Stanley Cobb Professor of Psychiatry, Harvard Medical School, Boston, urged caution when combining benzodiazepines with opioids.

“There are situations where you need to be circumspect about the use of benzodiazepines, and that’s clearly when people are being prescribed them in combination with other drugs that could be either sedating or respiratory depressant,” said Dr. Rosenbaum, who was not involved with the research.

“This paper reminds us that physicians need to be particularly vigilant about situations where patients might be combining the two agents,” he added.

Dr. Rosenbaum noted that patients who are using more medication than prescribed are at risk “for not appreciating the synergy” between the two treatments in terms of adverse events such as respiratory depression.

In addition, “if they’re intending to do themselves harm, the lethality of an overdose will be certainly far more than the benzodiazepines or opiates alone,” he said.

Another potential challenge for clinicians are situations in which patients are taking benzodiazepines for preexisting conditions that also require opiates. “Then you have to use special vigilance and try to use lowest doses to reduce the total burden of medication to minimize the potential risk,” said Dr. Rosenbaum.

The study was funded by the National Institutes of Health. Dr. Xu has reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Buprenorphine for the treatment of opioid-use disorder (OUD) may also mitigate the risk associated with concomitant benzodiazepine and Z-drug use, which is frequent in this patient population, new research suggests.

A case-crossover study of more than 20,000 participants with OUD showed that drug treatment days in which benzodiazepines and Z-drugs were taken were associated with an 88% increase in nonfatal overdose; buprenorphine appeared to reduce this risk by almost 40%.

“One of our two primary findings is that patients with opioid use disorder can still benefit substantially from buprenorphine treatment, even if they have benzodiazepines on board,” lead author Kevin Xu, MD, a resident at the Washington University, St. Louis, told this news organization.

The other key finding was that “not all benzodiazepines are equal” and that some are associated with higher risk than others, Dr. Xu added.

“If anything, patients who are on buprenorphine and benzodiazepines do not necessarily need to be abruptly tapered off their benzodiazepines. Our data actually demonstrate that there are safe avenues for them,” he added.

The findings were published online March 3 in the American Journal of Psychiatry.
 

Cloudy relationship

Buprenorphine is commonly used to treat patients with OUD because of its ability to decrease all-cause mortality. However, up to 30% of these patients also take benzodiazepines for comorbid mood and anxiety disorders, Dr. Xu noted.

In addition, recent research shows that benzodiazepine/Z-drug use is associated with a variety of potential adverse effects, including respiratory depression, overdose, and addiction risk.

The relationship between benzodiazepine use and buprenorphine treatment outcomes is poorly characterized in individuals with OUD. Although some studies suggest benzodiazepines may enhance retention in buprenorphine maintenance treatment, others suggest a link to increased adverse events, including all-cause mortality, drug-related poisonings, and accidental injury–related emergency department visits.

In addition, there has been little research on the potential adverse effects associated with use of selective benzodiazepine receptor modulators in patients with OUD. These so-called Z-drugs include zolpidem, zaleplon, and eszopiclone.

Nevertheless, previous research in the general population shows that these medications have a range of adverse effects similar to those of benzodiazepines, with comparable dose-response effects on all-cause mortality.

“The challenge for any clinician is that many patients who are addicted to opioids are also polysubstance users,” said Dr. Xu. “There are so many hopeful articles regarding the benefits of buprenorphine treatment in opioid use disorder patients, but it seems like the individuals with polysubstance use are largely ignored in the setting of the opioid epidemic.”

“And this is really the back story that got me inspired to study this particular topic,” he added.
 

Improve, nullify, or reverse?

Given these questions, the researchers set out to quantify the odds of nonfatal drug-related poisoning, including overdoses, associated with benzodiazepine or Z-drug use by patients with OUD who were also taking buprenorphine.

“While the drug-related poisoning variable encompasses opioid overdoses, we used a broad definition per CDC guidelines to also include other types of drug overdoses – including poisoning events involving stimulants, overdoses involving sedatives, and overdoses involving psychotropic prescription drugs” that are commonly used by patients with OUD, said Dr. Xu.

They also wanted to determine whether the use of benzodiazepines or Z-drugs would improve, nullify, or reverse the protective effect of buprenorphine. The researchers also evaluated whether different sedative and hypnotic subtypes of these drugs were associated with different poisoning risks.

The researchers analyzed pharmaceutical claims data from 304,676 individuals (aged 12-64 years) in the IBM MarketScan Commercial and Multi-State Medicaid Databases. All had received buprenorphine treatment for OUD between Jan. 1, 2006, and Dec. 31, 2016.

Buprenorphine use was converted to a daily milligram dose and was classified as either greater than 12 mg or less than or equal to 12 mg, because previous research suggests there may be differences in treatment retention associated with this dose. Given the case-control nature of the investigation, patients who did not experience a drug-related poisoning were excluded from the analysis.

The study’s primary unit of observation was person-days, which were those days during which patients were enrolled in a health insurance plan. Participants were evaluated for 1 year before their first drug-related poisoning and 1 year after their first such poisoning. The primary outcome was nonfatal drug-related poisonings, including overdoses. The primary exposure was determined on the basis of benzodiazepine or Z-drug prescriptions.

The daily dose of benzodiazepines or Z-drugs was standardized as a function of diazepam-equivalent milligrams. Doses were classified as either high dose (diazepam-equivalent mg dose >30 mg) or low dose (≤30 mg). The drugs were also distinguished on the basis of their pharmacologic properties, such as whether they were short-acting or long-acting.
 

37% risk reduction

Of the original cohort of 304,676 patients with OUD, the study’s final analytic sample included 23,036 patients (mean age, 30 years; 51% men), representing 14,213,075 person-days of insurance coverage. Of these, 2,210,927 person-days (15.6%) entailed claims for buprenorphine (mean daily dose, 15.4 mg; SD, 7.31 mg).

A total of 474,181 person-days included claims for benzodiazepines or Z-drugs with concurrent buprenorphine treatment. The mean daily dose of any benzodiazepine or Z-drug was 23.4 diazepam-milligram equivalents. The mean daily dose of short-acting benzodiazepines, long-acting benzodiazepines, and Z-drugs was 25.3, 31.3, and 4.9 diazepam-milligram equivalents, respectively.

Buprenorphine treatment days were associated with a 37% lower chance of drug-related poisoning (95% confidence interval, 0.60-0.66) in comparison with nontreatment days. On the other hand, the odds of poisoning increased by 81% on days on which patients were treated with Z-drugs or benzodiazepines (95% CI, 1.73-1.91).

Interestingly, individual analyses showed that benzodiazepine and Z-drug treatment days were associated with increased odds of poisoning events (odds ratio, 1.29; 95% CI, 1.19-1.39). Odds of poisoning events on benzodiazepine-only treatment days, on the other hand, were markedly lower (OR, 1.88; 95% CI, 1.78-1.98).

Subgroup analyses revealed that both short-acting and long-acting benzodiazepine treatment days were associated with comparably elevated odds of drug-related poisoning (OR, 1.86 and 1.68, respectively). High-dose benzodiazepine treatment days were associated with higher increased odds of a poisoning event (122%) in comparison with low-dose treatment days (78%).

High-dose, but not low-dose, benzodiazepine or Z-drug treatment was linked to increased poisonings when the drug was taken concurrently with buprenorphine (OR, 1.64; 95% CI, 1.39-1.93). However, the risk was still lower than the risk associated with taking the agents without concurrent treatment with buprenorphine (low-dose OR, 1.69; high-dose OR, 2.23).
 

‘Not all benzodiazepines are bad’

Dr. Xu noted that the findings have potentially important implications for clinical practice, beginning with the dose-dependent relationship between benzodiazepine/Z-drug use and drug-related poisonings among individuals with OUD. This indicates that lowering doses or shortening treatment duration may reduce risk, he said.

Similarly, the lower risk associated with long-acting benzodiazepines relative to short-acting beonzodiazepines – as well as the substantially lower risk associated with Z-drugs, compared with either short- or long-acting benzodiazepines – suggests that switching from benzodiazepines to long-acting agents or Z-drugs may lower the risk for overdose, he added.

“Clinicians are often challenged by patients with opioid use disorder who are also on benzodiazepines or Z-drugs. There’s an inclination to say no to them, because they’re too high risk to start buprenorphine maintenance, or abruptly taper the benzodiazepines, which can be very destabilizing,” he noted.

“Our data show that people on benzodiazepines can absolutely receive buprenorphine and still get some benefit,” Dr. Xu said. “In addition, not all benzodiazepines are bad for these individuals. There are safer formulations and safer doses, too.”

However, he added, he would not initiate benzodiazepine treatment if he didn’t have to, especially long-term treatment.

“One of the messages from our data is that this clearly contributes to higher overdose risk. But we often inherit patients who already have benzodiazepines on board, so we need to figure out what to do. That is the question that nobody had really clearly addressed prior to this study,” Dr. Xu concluded.
 

Vigilance needed

Commenting on the findings for this news organization, Jerrold F. Rosenbaum, MD, Stanley Cobb Professor of Psychiatry, Harvard Medical School, Boston, urged caution when combining benzodiazepines with opioids.

“There are situations where you need to be circumspect about the use of benzodiazepines, and that’s clearly when people are being prescribed them in combination with other drugs that could be either sedating or respiratory depressant,” said Dr. Rosenbaum, who was not involved with the research.

“This paper reminds us that physicians need to be particularly vigilant about situations where patients might be combining the two agents,” he added.

Dr. Rosenbaum noted that patients who are using more medication than prescribed are at risk “for not appreciating the synergy” between the two treatments in terms of adverse events such as respiratory depression.

In addition, “if they’re intending to do themselves harm, the lethality of an overdose will be certainly far more than the benzodiazepines or opiates alone,” he said.

Another potential challenge for clinicians are situations in which patients are taking benzodiazepines for preexisting conditions that also require opiates. “Then you have to use special vigilance and try to use lowest doses to reduce the total burden of medication to minimize the potential risk,” said Dr. Rosenbaum.

The study was funded by the National Institutes of Health. Dr. Xu has reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Buprenorphine for the treatment of opioid-use disorder (OUD) may also mitigate the risk associated with concomitant benzodiazepine and Z-drug use, which is frequent in this patient population, new research suggests.

A case-crossover study of more than 20,000 participants with OUD showed that drug treatment days in which benzodiazepines and Z-drugs were taken were associated with an 88% increase in nonfatal overdose; buprenorphine appeared to reduce this risk by almost 40%.

“One of our two primary findings is that patients with opioid use disorder can still benefit substantially from buprenorphine treatment, even if they have benzodiazepines on board,” lead author Kevin Xu, MD, a resident at the Washington University, St. Louis, told this news organization.

The other key finding was that “not all benzodiazepines are equal” and that some are associated with higher risk than others, Dr. Xu added.

“If anything, patients who are on buprenorphine and benzodiazepines do not necessarily need to be abruptly tapered off their benzodiazepines. Our data actually demonstrate that there are safe avenues for them,” he added.

The findings were published online March 3 in the American Journal of Psychiatry.
 

Cloudy relationship

Buprenorphine is commonly used to treat patients with OUD because of its ability to decrease all-cause mortality. However, up to 30% of these patients also take benzodiazepines for comorbid mood and anxiety disorders, Dr. Xu noted.

In addition, recent research shows that benzodiazepine/Z-drug use is associated with a variety of potential adverse effects, including respiratory depression, overdose, and addiction risk.

The relationship between benzodiazepine use and buprenorphine treatment outcomes is poorly characterized in individuals with OUD. Although some studies suggest benzodiazepines may enhance retention in buprenorphine maintenance treatment, others suggest a link to increased adverse events, including all-cause mortality, drug-related poisonings, and accidental injury–related emergency department visits.

In addition, there has been little research on the potential adverse effects associated with use of selective benzodiazepine receptor modulators in patients with OUD. These so-called Z-drugs include zolpidem, zaleplon, and eszopiclone.

Nevertheless, previous research in the general population shows that these medications have a range of adverse effects similar to those of benzodiazepines, with comparable dose-response effects on all-cause mortality.

“The challenge for any clinician is that many patients who are addicted to opioids are also polysubstance users,” said Dr. Xu. “There are so many hopeful articles regarding the benefits of buprenorphine treatment in opioid use disorder patients, but it seems like the individuals with polysubstance use are largely ignored in the setting of the opioid epidemic.”

“And this is really the back story that got me inspired to study this particular topic,” he added.
 

Improve, nullify, or reverse?

Given these questions, the researchers set out to quantify the odds of nonfatal drug-related poisoning, including overdoses, associated with benzodiazepine or Z-drug use by patients with OUD who were also taking buprenorphine.

“While the drug-related poisoning variable encompasses opioid overdoses, we used a broad definition per CDC guidelines to also include other types of drug overdoses – including poisoning events involving stimulants, overdoses involving sedatives, and overdoses involving psychotropic prescription drugs” that are commonly used by patients with OUD, said Dr. Xu.

They also wanted to determine whether the use of benzodiazepines or Z-drugs would improve, nullify, or reverse the protective effect of buprenorphine. The researchers also evaluated whether different sedative and hypnotic subtypes of these drugs were associated with different poisoning risks.

The researchers analyzed pharmaceutical claims data from 304,676 individuals (aged 12-64 years) in the IBM MarketScan Commercial and Multi-State Medicaid Databases. All had received buprenorphine treatment for OUD between Jan. 1, 2006, and Dec. 31, 2016.

Buprenorphine use was converted to a daily milligram dose and was classified as either greater than 12 mg or less than or equal to 12 mg, because previous research suggests there may be differences in treatment retention associated with this dose. Given the case-control nature of the investigation, patients who did not experience a drug-related poisoning were excluded from the analysis.

The study’s primary unit of observation was person-days, which were those days during which patients were enrolled in a health insurance plan. Participants were evaluated for 1 year before their first drug-related poisoning and 1 year after their first such poisoning. The primary outcome was nonfatal drug-related poisonings, including overdoses. The primary exposure was determined on the basis of benzodiazepine or Z-drug prescriptions.

The daily dose of benzodiazepines or Z-drugs was standardized as a function of diazepam-equivalent milligrams. Doses were classified as either high dose (diazepam-equivalent mg dose >30 mg) or low dose (≤30 mg). The drugs were also distinguished on the basis of their pharmacologic properties, such as whether they were short-acting or long-acting.
 

37% risk reduction

Of the original cohort of 304,676 patients with OUD, the study’s final analytic sample included 23,036 patients (mean age, 30 years; 51% men), representing 14,213,075 person-days of insurance coverage. Of these, 2,210,927 person-days (15.6%) entailed claims for buprenorphine (mean daily dose, 15.4 mg; SD, 7.31 mg).

A total of 474,181 person-days included claims for benzodiazepines or Z-drugs with concurrent buprenorphine treatment. The mean daily dose of any benzodiazepine or Z-drug was 23.4 diazepam-milligram equivalents. The mean daily dose of short-acting benzodiazepines, long-acting benzodiazepines, and Z-drugs was 25.3, 31.3, and 4.9 diazepam-milligram equivalents, respectively.

Buprenorphine treatment days were associated with a 37% lower chance of drug-related poisoning (95% confidence interval, 0.60-0.66) in comparison with nontreatment days. On the other hand, the odds of poisoning increased by 81% on days on which patients were treated with Z-drugs or benzodiazepines (95% CI, 1.73-1.91).

Interestingly, individual analyses showed that benzodiazepine and Z-drug treatment days were associated with increased odds of poisoning events (odds ratio, 1.29; 95% CI, 1.19-1.39). Odds of poisoning events on benzodiazepine-only treatment days, on the other hand, were markedly lower (OR, 1.88; 95% CI, 1.78-1.98).

Subgroup analyses revealed that both short-acting and long-acting benzodiazepine treatment days were associated with comparably elevated odds of drug-related poisoning (OR, 1.86 and 1.68, respectively). High-dose benzodiazepine treatment days were associated with higher increased odds of a poisoning event (122%) in comparison with low-dose treatment days (78%).

High-dose, but not low-dose, benzodiazepine or Z-drug treatment was linked to increased poisonings when the drug was taken concurrently with buprenorphine (OR, 1.64; 95% CI, 1.39-1.93). However, the risk was still lower than the risk associated with taking the agents without concurrent treatment with buprenorphine (low-dose OR, 1.69; high-dose OR, 2.23).
 

‘Not all benzodiazepines are bad’

Dr. Xu noted that the findings have potentially important implications for clinical practice, beginning with the dose-dependent relationship between benzodiazepine/Z-drug use and drug-related poisonings among individuals with OUD. This indicates that lowering doses or shortening treatment duration may reduce risk, he said.

Similarly, the lower risk associated with long-acting benzodiazepines relative to short-acting beonzodiazepines – as well as the substantially lower risk associated with Z-drugs, compared with either short- or long-acting benzodiazepines – suggests that switching from benzodiazepines to long-acting agents or Z-drugs may lower the risk for overdose, he added.

“Clinicians are often challenged by patients with opioid use disorder who are also on benzodiazepines or Z-drugs. There’s an inclination to say no to them, because they’re too high risk to start buprenorphine maintenance, or abruptly taper the benzodiazepines, which can be very destabilizing,” he noted.

“Our data show that people on benzodiazepines can absolutely receive buprenorphine and still get some benefit,” Dr. Xu said. “In addition, not all benzodiazepines are bad for these individuals. There are safer formulations and safer doses, too.”

However, he added, he would not initiate benzodiazepine treatment if he didn’t have to, especially long-term treatment.

“One of the messages from our data is that this clearly contributes to higher overdose risk. But we often inherit patients who already have benzodiazepines on board, so we need to figure out what to do. That is the question that nobody had really clearly addressed prior to this study,” Dr. Xu concluded.
 

Vigilance needed

Commenting on the findings for this news organization, Jerrold F. Rosenbaum, MD, Stanley Cobb Professor of Psychiatry, Harvard Medical School, Boston, urged caution when combining benzodiazepines with opioids.

“There are situations where you need to be circumspect about the use of benzodiazepines, and that’s clearly when people are being prescribed them in combination with other drugs that could be either sedating or respiratory depressant,” said Dr. Rosenbaum, who was not involved with the research.

“This paper reminds us that physicians need to be particularly vigilant about situations where patients might be combining the two agents,” he added.

Dr. Rosenbaum noted that patients who are using more medication than prescribed are at risk “for not appreciating the synergy” between the two treatments in terms of adverse events such as respiratory depression.

In addition, “if they’re intending to do themselves harm, the lethality of an overdose will be certainly far more than the benzodiazepines or opiates alone,” he said.

Another potential challenge for clinicians are situations in which patients are taking benzodiazepines for preexisting conditions that also require opiates. “Then you have to use special vigilance and try to use lowest doses to reduce the total burden of medication to minimize the potential risk,” said Dr. Rosenbaum.

The study was funded by the National Institutes of Health. Dr. Xu has reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Obstetrician/gynecologists are often first-line providers in addressing mental health concerns for our patients. Routine screening for intimate partner violence, obtaining a history of sexual assault, and assessing patients for postpartum depression are among the many tools that we use to ascertain the psychological well-being of cisgender women. As transgender patients continue to seek care from ob.gyns., it is vital that we not only screen transgender patients for depression and intimate partner violence, but also assess factors relating to social support.

Mental health disorders disproportionately affect the transgender population. A large online survey showed that 41% of transgender patients had experienced suicidality, with rates among transgender youth even higher.¹ While the rates of sexual violence are higher among LGBTQ patients compared with cisgender counterparts, the rate of sexual assault is as high as 47% in the transgender population.^2,3 Additional surveys and studies have demonstrated that more than 70% of transgender individuals report discrimination in school (K-12), 27% have lost their jobs because of their gender identity; and 30% have experienced homelessness at some point.³ Tragically, these rates are further affected by race and ethnicity with American Indian (65%), multiracial (59%), Middle Eastern (58%), and Black (53%) respondents in the survey stating they were assaulted at some point.³

In a prepandemic world, mental health for transgender patients was influenced by several factors, such as stigmatization, health care disparities, limited access to health care, prolonged exposure to discrimination, lack of a supportive environment, and history of trauma or violence. During the pandemic, these factors have been magnified. Furthermore, many of the supportive services such as group meetings at LGBTQ centers, networking events/conferences, LGBTQ pride events, and social gatherings at bars or restaurants have been postponed, reduced to accommodate social distancing measures, or moved to virtual platforms.

While the pandemic has led to increased unemployment rates, concerns over housing and rent payments, and limiting one’s social circle in the general population, these rates are increased among LGBTQ adults. Data are limited on how significantly the pandemic has affected LGBTQ adults, but an analysis conducted by the Kaiser Family Foundation found that 56% of LGBTQ adults reported that they or someone they know lost a job, compared with 44% of non-LGBTQ adults.⁴ In addition, 75% of LGBTQ adults report that the pandemic has negatively affected their mental health, compared with 49% of the non-LGBTQ population.⁴ To my dismay, I’ve seen these statistics reflected in my own patient population.

Given this knowledge, it is even more crucial that obstetrician/gynecologists screen for depression, substance use, and intimate partner violence, in addition to assessing the patient’s social determinants for overall well-being. These often include determining a patient’s living situation, employment status, familial support, and social support. In my practice, if concerns are raised in any of these areas, we have a streamlined referral system connecting patients to a variety of therapists, psychologists, and/or social workers, with close follow-up on either a weekly or monthly basis depending on the particular issue the patient is facing. While many patients may be hesitant to go to in-office appointments or where transportation poses a barrier, telemedicine visits are useful adjuncts to assess patient’s overall well-being.

While the pandemic has been extraordinarily difficult for us all, it is important for us to be even stronger advocates for communities that have experienced further challenges as a result of this global tragedy.
 

Dr. Brandt is an ob.gyn. and fellowship-trained gender-affirming surgeon in West Reading, Pa.

References

1. Karasic D. Mental health care for the adult transgender patient. In: Ferrando CA, ed. Comprehensive Care of the Transgender Patient. Philadelphia, PA: Elsevier; 2020:8-11.

2. Black MC et al. The National Intimate Partner and Sexual Violence Survey (NISVS): 2010 Summary Report. Atlanta: National Center for Injury Prevention and Control, Centers for Disease Control and Prevention; 2011.

3. James SE et al. The Report of the 2015 U.S. Transgender Survey. Washington, DC: National Center for Transgender Equality; 2016.

4. Dawson L et al. The impact of the COVID-19 pandemic on LGBT people. KFF COVID-19 Vaccine Monitor. Kaiser Family Foundation. March 11, 2021.

Obstetrician/gynecologists are often first-line providers in addressing mental health concerns for our patients. Routine screening for intimate partner violence, obtaining a history of sexual assault, and assessing patients for postpartum depression are among the many tools that we use to ascertain the psychological well-being of cisgender women. As transgender patients continue to seek care from ob.gyns., it is vital that we not only screen transgender patients for depression and intimate partner violence, but also assess factors relating to social support.

Mental health disorders disproportionately affect the transgender population. A large online survey showed that 41% of transgender patients had experienced suicidality, with rates among transgender youth even higher.¹ While the rates of sexual violence are higher among LGBTQ patients compared with cisgender counterparts, the rate of sexual assault is as high as 47% in the transgender population.^2,3 Additional surveys and studies have demonstrated that more than 70% of transgender individuals report discrimination in school (K-12), 27% have lost their jobs because of their gender identity; and 30% have experienced homelessness at some point.³ Tragically, these rates are further affected by race and ethnicity with American Indian (65%), multiracial (59%), Middle Eastern (58%), and Black (53%) respondents in the survey stating they were assaulted at some point.³

In a prepandemic world, mental health for transgender patients was influenced by several factors, such as stigmatization, health care disparities, limited access to health care, prolonged exposure to discrimination, lack of a supportive environment, and history of trauma or violence. During the pandemic, these factors have been magnified. Furthermore, many of the supportive services such as group meetings at LGBTQ centers, networking events/conferences, LGBTQ pride events, and social gatherings at bars or restaurants have been postponed, reduced to accommodate social distancing measures, or moved to virtual platforms.

While the pandemic has led to increased unemployment rates, concerns over housing and rent payments, and limiting one’s social circle in the general population, these rates are increased among LGBTQ adults. Data are limited on how significantly the pandemic has affected LGBTQ adults, but an analysis conducted by the Kaiser Family Foundation found that 56% of LGBTQ adults reported that they or someone they know lost a job, compared with 44% of non-LGBTQ adults.⁴ In addition, 75% of LGBTQ adults report that the pandemic has negatively affected their mental health, compared with 49% of the non-LGBTQ population.⁴ To my dismay, I’ve seen these statistics reflected in my own patient population.

Given this knowledge, it is even more crucial that obstetrician/gynecologists screen for depression, substance use, and intimate partner violence, in addition to assessing the patient’s social determinants for overall well-being. These often include determining a patient’s living situation, employment status, familial support, and social support. In my practice, if concerns are raised in any of these areas, we have a streamlined referral system connecting patients to a variety of therapists, psychologists, and/or social workers, with close follow-up on either a weekly or monthly basis depending on the particular issue the patient is facing. While many patients may be hesitant to go to in-office appointments or where transportation poses a barrier, telemedicine visits are useful adjuncts to assess patient’s overall well-being.

While the pandemic has been extraordinarily difficult for us all, it is important for us to be even stronger advocates for communities that have experienced further challenges as a result of this global tragedy.
 

Dr. Brandt is an ob.gyn. and fellowship-trained gender-affirming surgeon in West Reading, Pa.

References

1. Karasic D. Mental health care for the adult transgender patient. In: Ferrando CA, ed. Comprehensive Care of the Transgender Patient. Philadelphia, PA: Elsevier; 2020:8-11.

2. Black MC et al. The National Intimate Partner and Sexual Violence Survey (NISVS): 2010 Summary Report. Atlanta: National Center for Injury Prevention and Control, Centers for Disease Control and Prevention; 2011.

3. James SE et al. The Report of the 2015 U.S. Transgender Survey. Washington, DC: National Center for Transgender Equality; 2016.

4. Dawson L et al. The impact of the COVID-19 pandemic on LGBT people. KFF COVID-19 Vaccine Monitor. Kaiser Family Foundation. March 11, 2021.

Obstetrician/gynecologists are often first-line providers in addressing mental health concerns for our patients. Routine screening for intimate partner violence, obtaining a history of sexual assault, and assessing patients for postpartum depression are among the many tools that we use to ascertain the psychological well-being of cisgender women. As transgender patients continue to seek care from ob.gyns., it is vital that we not only screen transgender patients for depression and intimate partner violence, but also assess factors relating to social support.

Mental health disorders disproportionately affect the transgender population. A large online survey showed that 41% of transgender patients had experienced suicidality, with rates among transgender youth even higher.¹ While the rates of sexual violence are higher among LGBTQ patients compared with cisgender counterparts, the rate of sexual assault is as high as 47% in the transgender population.^2,3 Additional surveys and studies have demonstrated that more than 70% of transgender individuals report discrimination in school (K-12), 27% have lost their jobs because of their gender identity; and 30% have experienced homelessness at some point.³ Tragically, these rates are further affected by race and ethnicity with American Indian (65%), multiracial (59%), Middle Eastern (58%), and Black (53%) respondents in the survey stating they were assaulted at some point.³

In a prepandemic world, mental health for transgender patients was influenced by several factors, such as stigmatization, health care disparities, limited access to health care, prolonged exposure to discrimination, lack of a supportive environment, and history of trauma or violence. During the pandemic, these factors have been magnified. Furthermore, many of the supportive services such as group meetings at LGBTQ centers, networking events/conferences, LGBTQ pride events, and social gatherings at bars or restaurants have been postponed, reduced to accommodate social distancing measures, or moved to virtual platforms.

While the pandemic has led to increased unemployment rates, concerns over housing and rent payments, and limiting one’s social circle in the general population, these rates are increased among LGBTQ adults. Data are limited on how significantly the pandemic has affected LGBTQ adults, but an analysis conducted by the Kaiser Family Foundation found that 56% of LGBTQ adults reported that they or someone they know lost a job, compared with 44% of non-LGBTQ adults.⁴ In addition, 75% of LGBTQ adults report that the pandemic has negatively affected their mental health, compared with 49% of the non-LGBTQ population.⁴ To my dismay, I’ve seen these statistics reflected in my own patient population.

Given this knowledge, it is even more crucial that obstetrician/gynecologists screen for depression, substance use, and intimate partner violence, in addition to assessing the patient’s social determinants for overall well-being. These often include determining a patient’s living situation, employment status, familial support, and social support. In my practice, if concerns are raised in any of these areas, we have a streamlined referral system connecting patients to a variety of therapists, psychologists, and/or social workers, with close follow-up on either a weekly or monthly basis depending on the particular issue the patient is facing. While many patients may be hesitant to go to in-office appointments or where transportation poses a barrier, telemedicine visits are useful adjuncts to assess patient’s overall well-being.

While the pandemic has been extraordinarily difficult for us all, it is important for us to be even stronger advocates for communities that have experienced further challenges as a result of this global tragedy.
 

Dr. Brandt is an ob.gyn. and fellowship-trained gender-affirming surgeon in West Reading, Pa.

References

1. Karasic D. Mental health care for the adult transgender patient. In: Ferrando CA, ed. Comprehensive Care of the Transgender Patient. Philadelphia, PA: Elsevier; 2020:8-11.

2. Black MC et al. The National Intimate Partner and Sexual Violence Survey (NISVS): 2010 Summary Report. Atlanta: National Center for Injury Prevention and Control, Centers for Disease Control and Prevention; 2011.

3. James SE et al. The Report of the 2015 U.S. Transgender Survey. Washington, DC: National Center for Transgender Equality; 2016.

4. Dawson L et al. The impact of the COVID-19 pandemic on LGBT people. KFF COVID-19 Vaccine Monitor. Kaiser Family Foundation. March 11, 2021.

Recommendations, as well as conspiracy theories about COVID-19, have changed at distressing rates over the past year. No disease has ever been more politicized, or more polarizing.

Experts, as well as the least educated, take a stand on what they believe is the most important way to prevent and treat this virus. Many medications have been touted as cures, even when doctors and scientists say they don’t work.

Just recently, a study was published revealing that ivermectin is not effective as a COVID-19 treatment while people continue to claim it works. It has never been more important for doctors, and especially family physicians, to have accurate and updated guidelines.

The NIH and CDC have been publishing recommendations and guidelines for the prevention and treatment of COVID-19 since the start of the pandemic. Like any new disease, these have been changing to keep up as new knowledge related to the disease becomes available.
 

NIH updates treatment guidelines

A recent update to the NIH COVID-19 treatment guidelines was published on March 5, 2021. While the complete guidelines are quite extensive, spanning over 200 pages, it’s most important to understand the most recent updates in them.

Since preventative medicine is an integral part of primary care, it is important to note that no medications have been advised to prevent infection with COVID-19. In fact, taking drugs for pre-exposure prophylaxis (PrEp) is not recommended even in the highest-risk patients, such as health care workers.

In the updated guidelines, tocilizumab in a single IV dose of 8 mg/kg up to a maximum of 800 mg can be given only in combination with dexamethasone (or equivalent corticosteroid) in certain hospitalized patients exhibiting rapid respiratory decompensation. These patients include recently hospitalized patients who have been admitted to the ICU within the previous 24 hours and now require mechanical ventilation or high-flow oxygen via nasal cannula. Those not in the ICU who require rapidly increasing oxygen levels and have significantly increased levels of inflammatory markers should also receive this therapy. In the new guidance, the NIH recommends treating other hospitalized patients who require oxygen with remdesivir, remdesivir + dexamethasone, or dexamethasone alone.

In outpatients, those who have mild to moderate infection and are at increased risk of developing severe disease and/or hospitalization can be treated with bamlanivimab 700 mg + etesevimab 1,400 mg. This should be started as soon as possible after a confirmed diagnosis and within 10 days of symptom onset, according to the NIH recommendations. There is no evidence to support its use in patients hospitalized because of infection. However, it can be used in patients hospitalized for other reasons who have mild to moderate infection, but should be reserved – because of limited supply – for those with the highest risk of complications.
 

Hydroxychloroquine and casirivimab + imdevimab

One medication that has been touted in the media as a tool to treat COVID-19 has been hydroxychloroquine. Past guidelines recommended against this medication as a treatment because it lacked efficacy and posed risks for no therapeutic benefit. The most recent guidelines also recommend against the use of hydroxychloroquine for pre- and postexposure prophylaxis.

Casirivimab + imdevimab has been another talked about therapy. However, current guidelines recommend against its use in hospitalized patients. In addition, it is advised that hospitalized patients be enrolled in a clinical trial to receive it.

Since the pandemic began, the world has seen more than 120 million infections and more than 2 million deaths. Family physicians have a vital role to play as we are often the first ones patients turn to for treatment and advice. It is imperative we stay current with the guidelines and follow the most recent updates as research data are published.
 

Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J. You can contact her at [email protected].

Recommendations, as well as conspiracy theories about COVID-19, have changed at distressing rates over the past year. No disease has ever been more politicized, or more polarizing.

Experts, as well as the least educated, take a stand on what they believe is the most important way to prevent and treat this virus. Many medications have been touted as cures, even when doctors and scientists say they don’t work.

Just recently, a study was published revealing that ivermectin is not effective as a COVID-19 treatment while people continue to claim it works. It has never been more important for doctors, and especially family physicians, to have accurate and updated guidelines.

The NIH and CDC have been publishing recommendations and guidelines for the prevention and treatment of COVID-19 since the start of the pandemic. Like any new disease, these have been changing to keep up as new knowledge related to the disease becomes available.
 

NIH updates treatment guidelines

A recent update to the NIH COVID-19 treatment guidelines was published on March 5, 2021. While the complete guidelines are quite extensive, spanning over 200 pages, it’s most important to understand the most recent updates in them.

Since preventative medicine is an integral part of primary care, it is important to note that no medications have been advised to prevent infection with COVID-19. In fact, taking drugs for pre-exposure prophylaxis (PrEp) is not recommended even in the highest-risk patients, such as health care workers.

In the updated guidelines, tocilizumab in a single IV dose of 8 mg/kg up to a maximum of 800 mg can be given only in combination with dexamethasone (or equivalent corticosteroid) in certain hospitalized patients exhibiting rapid respiratory decompensation. These patients include recently hospitalized patients who have been admitted to the ICU within the previous 24 hours and now require mechanical ventilation or high-flow oxygen via nasal cannula. Those not in the ICU who require rapidly increasing oxygen levels and have significantly increased levels of inflammatory markers should also receive this therapy. In the new guidance, the NIH recommends treating other hospitalized patients who require oxygen with remdesivir, remdesivir + dexamethasone, or dexamethasone alone.

In outpatients, those who have mild to moderate infection and are at increased risk of developing severe disease and/or hospitalization can be treated with bamlanivimab 700 mg + etesevimab 1,400 mg. This should be started as soon as possible after a confirmed diagnosis and within 10 days of symptom onset, according to the NIH recommendations. There is no evidence to support its use in patients hospitalized because of infection. However, it can be used in patients hospitalized for other reasons who have mild to moderate infection, but should be reserved – because of limited supply – for those with the highest risk of complications.
 

Hydroxychloroquine and casirivimab + imdevimab

One medication that has been touted in the media as a tool to treat COVID-19 has been hydroxychloroquine. Past guidelines recommended against this medication as a treatment because it lacked efficacy and posed risks for no therapeutic benefit. The most recent guidelines also recommend against the use of hydroxychloroquine for pre- and postexposure prophylaxis.

Casirivimab + imdevimab has been another talked about therapy. However, current guidelines recommend against its use in hospitalized patients. In addition, it is advised that hospitalized patients be enrolled in a clinical trial to receive it.

Since the pandemic began, the world has seen more than 120 million infections and more than 2 million deaths. Family physicians have a vital role to play as we are often the first ones patients turn to for treatment and advice. It is imperative we stay current with the guidelines and follow the most recent updates as research data are published.
 

Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J. You can contact her at [email protected].

Recommendations, as well as conspiracy theories about COVID-19, have changed at distressing rates over the past year. No disease has ever been more politicized, or more polarizing.

Experts, as well as the least educated, take a stand on what they believe is the most important way to prevent and treat this virus. Many medications have been touted as cures, even when doctors and scientists say they don’t work.

Just recently, a study was published revealing that ivermectin is not effective as a COVID-19 treatment while people continue to claim it works. It has never been more important for doctors, and especially family physicians, to have accurate and updated guidelines.

The NIH and CDC have been publishing recommendations and guidelines for the prevention and treatment of COVID-19 since the start of the pandemic. Like any new disease, these have been changing to keep up as new knowledge related to the disease becomes available.
 

NIH updates treatment guidelines

A recent update to the NIH COVID-19 treatment guidelines was published on March 5, 2021. While the complete guidelines are quite extensive, spanning over 200 pages, it’s most important to understand the most recent updates in them.

Since preventative medicine is an integral part of primary care, it is important to note that no medications have been advised to prevent infection with COVID-19. In fact, taking drugs for pre-exposure prophylaxis (PrEp) is not recommended even in the highest-risk patients, such as health care workers.

In the updated guidelines, tocilizumab in a single IV dose of 8 mg/kg up to a maximum of 800 mg can be given only in combination with dexamethasone (or equivalent corticosteroid) in certain hospitalized patients exhibiting rapid respiratory decompensation. These patients include recently hospitalized patients who have been admitted to the ICU within the previous 24 hours and now require mechanical ventilation or high-flow oxygen via nasal cannula. Those not in the ICU who require rapidly increasing oxygen levels and have significantly increased levels of inflammatory markers should also receive this therapy. In the new guidance, the NIH recommends treating other hospitalized patients who require oxygen with remdesivir, remdesivir + dexamethasone, or dexamethasone alone.

In outpatients, those who have mild to moderate infection and are at increased risk of developing severe disease and/or hospitalization can be treated with bamlanivimab 700 mg + etesevimab 1,400 mg. This should be started as soon as possible after a confirmed diagnosis and within 10 days of symptom onset, according to the NIH recommendations. There is no evidence to support its use in patients hospitalized because of infection. However, it can be used in patients hospitalized for other reasons who have mild to moderate infection, but should be reserved – because of limited supply – for those with the highest risk of complications.
 

Hydroxychloroquine and casirivimab + imdevimab

One medication that has been touted in the media as a tool to treat COVID-19 has been hydroxychloroquine. Past guidelines recommended against this medication as a treatment because it lacked efficacy and posed risks for no therapeutic benefit. The most recent guidelines also recommend against the use of hydroxychloroquine for pre- and postexposure prophylaxis.

Casirivimab + imdevimab has been another talked about therapy. However, current guidelines recommend against its use in hospitalized patients. In addition, it is advised that hospitalized patients be enrolled in a clinical trial to receive it.

Since the pandemic began, the world has seen more than 120 million infections and more than 2 million deaths. Family physicians have a vital role to play as we are often the first ones patients turn to for treatment and advice. It is imperative we stay current with the guidelines and follow the most recent updates as research data are published.
 

Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J. You can contact her at [email protected].

U.S. regulators are stepping up scrutiny of therapies that were granted an accelerated approval to treat cancers on the basis of surrogate endpoints but have failed to show clinical or survival benefits upon more extensive testing.

At issue are a number of cancer indications for immunotherapies. Four have already been withdrawn (voluntarily by the manufacturer), and six more will be reviewed at an upcoming meeting.

In recent years, the US Food and Drug Administration has granted accelerated approvals to oncology medicines on the basis of evidence that suggests a benefit for patients. Examples of such evidence relate to response rates and estimates of tumor shrinkage. But these approvals are granted on the condition that the manufacturer conducts larger clinical trials that show clinical benefit, including benefit in overall survival.

Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence, has argued that the point of these conditional approvals is to find acceptable surrogate markers to allow people with “desperate illnesses” to have access to potentially helpful drugs while work continues to determine the drug’s actual benefit to patients.

Oncologists are now questioning whether the FDA has become too lenient in its approach, Daniel A. Goldstein, MD, a senior physician in medical oncology and internal medicine at the Rabin Medical Center, Petah Tikva, Israel, told this news organization.

“The main two things you want from a cancer drug is to live longer and live a higher quality of life,” said Goldstein. “But these endpoints that they’ve been using over the past few years are not really giving us confidence that these drugs are actually going to help to live longer or better.”

Dr. Pazdur said the FDA will consider withdrawing its accelerated approvals when results of further studies do not confirm expected benefit for patients.

“This is like the pendulum has swung as far as it was going to swing and now is on the backswing,” said Dr. Goldstein, also of the department of health policy and management at the University of North Carolina at Chapel Hill. “You could call this a watershed moment.”

Although there’s near universal interest in allowing people with advanced cancer access to promising medicines, there’s also rising concern about exposing patients needlessly to costly drugs with potentially tough side effects. That may prompt a shift in the standards U.S. regulators apply to cancer medicines, Dr. Goldstein said.
 

Indications withdrawn and under review

In a meeting scheduled for April 27-29, the FDA’s Oncologic Drugs Advisory Committee will review indications granted through the accelerated approval process for three immunotherapies: pembrolizumab (Keytruda), atezolizumab (Tecentriq), and nivolumab (Opdivo).

It is part of an industry-wide evaluation of accelerated approvals for cancer indications in which confirmatory trials did not confirm clinical benefit, the FDA noted.

The process has already led to voluntary withdrawals of four cancer indications by the manufacturers, including one indication each for pembrolizumab, atezolizumab, and nivolumab, and one for durvalumab (Imfinzi).

All of these immunotherapies are approved for numerous cancer indications, and they all remain on the market. It is only the U.S. approvals for particular cancer indications that have been withdrawn.

In the past, olaratumab (Lartruvo) was withdrawn from the market altogether. The FDA granted accelerated approval of the drug for soft tissue sarcoma, but clinical benefit was not confirmed in a phase 3 trial.
 

Issue highlighted by Dr. Prasad and Dr. Gyawali

In recent years, much of the attention on accelerated approvals was spurred by the work of a few researchers, particularly Vinay Prasad, MD, MPH, associate professor in the department of epidemiology and biostatistics, University of California, San Francisco, and Bishal Gyawali, MD, PhD, from Queen’s University Cancer Research Institute, Kingston, Ont. (Both are regular contributors to the oncology section of this news organization.)

Dr. Goldstein made this point in a tweet about the FDA’s announcement of the April ODAC meetings:

“Well done to @oncology_bg and @VPrasadMDMPH among others for highlighting in their papers that the FDA wasn’t properly evaluating accelerated approval drugs.

FDA have listened.

And I thought that the impact of academia was limited!”

Dr. Prasad has made the case for closer scrutiny of accelerated approvals in a number of journal articles and in his 2020 book, “Malignant: How Bad Policy and Bad Evidence Harm People with Cancer,” published by Johns Hopkins University Press.

The book includes highlights of a 2016 article published in Mayo Clinic Proceedings that focused on surrogate endpoints used for FDA approvals. In the article, Dr. Prasad and his coauthor report that they did not find formal analyses of the strength of the surrogate-survival correlation in 14 of 25 cases of accelerated approvals (56%) and in 11 of 30 traditional approvals (37%).

“Our results were concerning. They imply that many surrogates are based on little more than a gut feeling. You might rationalize that and argue a gut feeling is the same as ‘reasonably likely to predict,’ but no reasonable person could think a gut feeling means established,” Dr. Prasad writes in his book. “Our result suggests the FDA is using surrogate endpoints far beyond what may be fair or reasonable.”

Dr. Gyawali has argued that the process by which the FDA assesses cancer drugs for approvals has undergone a profound shift. He has most recently remarked on this in an October 2020 commentary on Medscape.

“Until the recent floodgate of approvals based on response rates from single-arm trials, the majority of cancer therapy decisions were supported by evidence generated from randomized controlled trials (RCTs),” Dr. Gyawali wrote. “The evidence base to support clinical decisions in managing therapeutic side effects has been comparatively sparse.”
 

Accelerated approval to improve access

The FDA has struggled for about 2 decades with questions of where to set the bar on evidence for promising cancer drugs.

The agency’s accelerated approval program for drugs began in 1992. During the first decade, the focus was largely on medicines related to HIV.

In the early 2000s, oncology drugs began to dominate the program.

Dr. Pazdur has presided over the FDA’s marked changes regarding the use of surrogate markers when weighing whether to allow sales of cancer medicines. Formerly a professor at the University of Texas MD Anderson Cancer Center, Houston, Dr. Pazdur joined the FDA as director of the Division of Oncology Drug Products in 1999.

Soon after his appointment, he had to field inquiries from pharmaceutical companies about how much evidence they needed to receive accelerated approvals.

Early on, he publicly expressed impatience about the drugmakers’ approach. “The purpose of accelerated approval was not accelerated drug company profits,” Dr. Padzur said at a 2004 ODAC meeting.

Rather, the point is to allow access to potentially helpful drugs while work continues to determine their actual benefit to patients, he explained.

“It wasn’t a license to do less, less, less, and less to a point now that we may be getting companies that are coming in” intent on determining the minimum evidence the FDA will take, Dr. Pazdur said. “It shouldn’t be what is the lowest. It is what is a sufficient amount to give patients and physicians a real understanding of what their drug will do.”

In a 2016 interview with The New York Times, Dr. Pazdur said that his views on cancer drug approvals have evolved with time. He described himself as being “on a jihad to streamline the review process and get things out the door faster.”

“I have evolved from regulator to regulator-advocate,” Dr. Pazdur told the newspaper.

His attitude reflected his personal experience in losing his wife to ovarian cancer in 2015, as well as shifts in science and law. In 2012, Congress passed a law that gave the FDA new resources to speed medicines for life-threatening diseases to market. In addition, advances in genetics appeared to be making some medications more effective and easier to test, Dr. Pazdur said in The New York Times interview.
 

Withdrawals seen as sign of success

Since the program’s inception, only 6% of accelerated approvals for oncology indications have been withdrawn, the FDA said.

It would be a sign that the program is working if the April meetings lead to further withdrawals of indications that have been granted accelerated approval, Julie R. Gralow, MD, chief medical officer of the American Society of Clinical Oncology, said in an interview with this news organization.

“It shouldn’t be seen as a failure,” Dr. Gralow said.

In her own practice at the Fred Hutchinson Cancer Research Center, Seattle, she has seen the value of emerging therapies for patients fighting advanced cancers. During her 25 years of clinical practice in an academic setting, she has gained access to drugs through single-patient investigative new drug applications.

However, this path is not an option for many patients who undergo treatment in facilities other than academic centers, she commented. She noted that the accelerated approval process is a way to expand access to emerging medicines, but she sees a need for caution in the use of drugs that have been given only this conditional approval. She emphasizes that such drugs may be suitable only for certain patients.

“I would say that, for metastatic patients, patients with incurable disease, we are willing to take some risk,” Dr. Gralow said. “We don’t have other options. They can’t wait the years that it would take to get a drug approved.”

One such patient is David Mitchell, who serves as the consumer representative on ODAC. He told this news organization that he is taking three drugs for multiple myeloma that received accelerated approvals: pomalidomide, bortezomib, and daratumumab.

“I want the FDA to have the option to approve drugs in an accelerated pathway, because as a patient taking three drugs granted accelerated approval, I’m benefiting – I’ve lived the benefit,” Mr. Mitchell said, “and I want other patients to have the opportunity to have that benefit.”

He believes that the FDA’s approach regarding accelerated approvals serves to get potentially beneficial medicines to patients who have few options and also fulfills the FDA’s mandate to protect the public from treatments that have little benefit but can cause harm.

Accelerated approval also offers needed flexibility to drugmakers as they develop more specifically targeted drugs for diseases that affect relatively few people, such as multiple myeloma, he said. “As the targeting of your therapies gets tighter and for smaller groups of patients, you have a harder time following the traditional model,” such as conducting large, double-blind, placebo-controlled trials that may indicate increased overall survival, he said.

“To me, this is the way the FDA intended it to work,” he added. “It’s going to offer the accelerated approval based on a surrogate endpoint for a safe drug, but it’s going to require the confirmatory trial, and if the confirmatory trial fails, it will pull the drug off the market.”

Some medicines that have received accelerated approvals may ultimately be found not to benefit patients, Mr. Mitchell acknowledged. But people in his situation, whose disease has progressed despite treatments, may want to take that risk, he added.


 

Four cancer indications recently withdrawn voluntarily by the manufacturer

• December 2020: Nivolumab for the treatment of patients with metastatic small cell lung cancer with progression after platinum-based chemotherapy and at least one other line of therapy (Bristol Myers Squibb).
• February 2021: Durvalumab for the treatment of patients with locally advanced or metastatic urothelial carcinoma whose disease has progressed during or following platinum-based chemotherapy or within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy (AstraZeneca).
• March 2021: Pembrolizumab for the treatment of patients with metastatic small cell lung cancer with disease progression on or after platinum-based chemotherapy and at least one other prior line of therapy (Merck).
• March 2021: Atezolizumab for treatment of patients with locally advanced or metastatic urothelial carcinoma who experience disease progression during or following platinum-containing atezolizumab chemotherapy or disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy (Genentech).

Six cancer indications under review at the April 2021 ODAC meeting

• Atezolizumab indicated in combination with protein-bound  for the treatment of adults with unresectable locally advanced or metastatic triple-negative  whose tumors express PD-L1 (PD-L1 stained tumor-infiltrating immune cells of any intensity covering ≥1% of the tumor area), as determined by an FDA-approved test.
• Atezolizumab indicated for patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing chemotherapy.
• Pembrolizumab indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing chemotherapy.
• Pembrolizumab indicated for the treatment of patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma whose tumors express PD-L1 (Combined Positive Score ≥1), as determined by an FDA-approved test, with disease progression on or after two or more prior lines of therapy including fluoropyrimidine- and platinum-containing chemotherapy and if appropriate, HER2/neu-targeted therapy.
• Pembrolizumab indicated for the treatment of patients with  who have been previously treated with .
• Nivolumab indicated as a single agent for the treatment of patients with hepatocellular carcinoma who have been previously treated with sorafenib.

A version of this article first appeared on Medscape.com.

U.S. regulators are stepping up scrutiny of therapies that were granted an accelerated approval to treat cancers on the basis of surrogate endpoints but have failed to show clinical or survival benefits upon more extensive testing.

At issue are a number of cancer indications for immunotherapies. Four have already been withdrawn (voluntarily by the manufacturer), and six more will be reviewed at an upcoming meeting.

In recent years, the US Food and Drug Administration has granted accelerated approvals to oncology medicines on the basis of evidence that suggests a benefit for patients. Examples of such evidence relate to response rates and estimates of tumor shrinkage. But these approvals are granted on the condition that the manufacturer conducts larger clinical trials that show clinical benefit, including benefit in overall survival.

Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence, has argued that the point of these conditional approvals is to find acceptable surrogate markers to allow people with “desperate illnesses” to have access to potentially helpful drugs while work continues to determine the drug’s actual benefit to patients.

Oncologists are now questioning whether the FDA has become too lenient in its approach, Daniel A. Goldstein, MD, a senior physician in medical oncology and internal medicine at the Rabin Medical Center, Petah Tikva, Israel, told this news organization.

“The main two things you want from a cancer drug is to live longer and live a higher quality of life,” said Goldstein. “But these endpoints that they’ve been using over the past few years are not really giving us confidence that these drugs are actually going to help to live longer or better.”

Dr. Pazdur said the FDA will consider withdrawing its accelerated approvals when results of further studies do not confirm expected benefit for patients.

“This is like the pendulum has swung as far as it was going to swing and now is on the backswing,” said Dr. Goldstein, also of the department of health policy and management at the University of North Carolina at Chapel Hill. “You could call this a watershed moment.”

Although there’s near universal interest in allowing people with advanced cancer access to promising medicines, there’s also rising concern about exposing patients needlessly to costly drugs with potentially tough side effects. That may prompt a shift in the standards U.S. regulators apply to cancer medicines, Dr. Goldstein said.
 

Indications withdrawn and under review

In a meeting scheduled for April 27-29, the FDA’s Oncologic Drugs Advisory Committee will review indications granted through the accelerated approval process for three immunotherapies: pembrolizumab (Keytruda), atezolizumab (Tecentriq), and nivolumab (Opdivo).

It is part of an industry-wide evaluation of accelerated approvals for cancer indications in which confirmatory trials did not confirm clinical benefit, the FDA noted.

The process has already led to voluntary withdrawals of four cancer indications by the manufacturers, including one indication each for pembrolizumab, atezolizumab, and nivolumab, and one for durvalumab (Imfinzi).

All of these immunotherapies are approved for numerous cancer indications, and they all remain on the market. It is only the U.S. approvals for particular cancer indications that have been withdrawn.

In the past, olaratumab (Lartruvo) was withdrawn from the market altogether. The FDA granted accelerated approval of the drug for soft tissue sarcoma, but clinical benefit was not confirmed in a phase 3 trial.
 

Issue highlighted by Dr. Prasad and Dr. Gyawali

In recent years, much of the attention on accelerated approvals was spurred by the work of a few researchers, particularly Vinay Prasad, MD, MPH, associate professor in the department of epidemiology and biostatistics, University of California, San Francisco, and Bishal Gyawali, MD, PhD, from Queen’s University Cancer Research Institute, Kingston, Ont. (Both are regular contributors to the oncology section of this news organization.)

Dr. Goldstein made this point in a tweet about the FDA’s announcement of the April ODAC meetings:

“Well done to @oncology_bg and @VPrasadMDMPH among others for highlighting in their papers that the FDA wasn’t properly evaluating accelerated approval drugs.

FDA have listened.

And I thought that the impact of academia was limited!”

Dr. Prasad has made the case for closer scrutiny of accelerated approvals in a number of journal articles and in his 2020 book, “Malignant: How Bad Policy and Bad Evidence Harm People with Cancer,” published by Johns Hopkins University Press.

The book includes highlights of a 2016 article published in Mayo Clinic Proceedings that focused on surrogate endpoints used for FDA approvals. In the article, Dr. Prasad and his coauthor report that they did not find formal analyses of the strength of the surrogate-survival correlation in 14 of 25 cases of accelerated approvals (56%) and in 11 of 30 traditional approvals (37%).

“Our results were concerning. They imply that many surrogates are based on little more than a gut feeling. You might rationalize that and argue a gut feeling is the same as ‘reasonably likely to predict,’ but no reasonable person could think a gut feeling means established,” Dr. Prasad writes in his book. “Our result suggests the FDA is using surrogate endpoints far beyond what may be fair or reasonable.”

Dr. Gyawali has argued that the process by which the FDA assesses cancer drugs for approvals has undergone a profound shift. He has most recently remarked on this in an October 2020 commentary on Medscape.

“Until the recent floodgate of approvals based on response rates from single-arm trials, the majority of cancer therapy decisions were supported by evidence generated from randomized controlled trials (RCTs),” Dr. Gyawali wrote. “The evidence base to support clinical decisions in managing therapeutic side effects has been comparatively sparse.”
 

Accelerated approval to improve access

The FDA has struggled for about 2 decades with questions of where to set the bar on evidence for promising cancer drugs.

The agency’s accelerated approval program for drugs began in 1992. During the first decade, the focus was largely on medicines related to HIV.

In the early 2000s, oncology drugs began to dominate the program.

Dr. Pazdur has presided over the FDA’s marked changes regarding the use of surrogate markers when weighing whether to allow sales of cancer medicines. Formerly a professor at the University of Texas MD Anderson Cancer Center, Houston, Dr. Pazdur joined the FDA as director of the Division of Oncology Drug Products in 1999.

Soon after his appointment, he had to field inquiries from pharmaceutical companies about how much evidence they needed to receive accelerated approvals.

Early on, he publicly expressed impatience about the drugmakers’ approach. “The purpose of accelerated approval was not accelerated drug company profits,” Dr. Padzur said at a 2004 ODAC meeting.

Rather, the point is to allow access to potentially helpful drugs while work continues to determine their actual benefit to patients, he explained.

“It wasn’t a license to do less, less, less, and less to a point now that we may be getting companies that are coming in” intent on determining the minimum evidence the FDA will take, Dr. Pazdur said. “It shouldn’t be what is the lowest. It is what is a sufficient amount to give patients and physicians a real understanding of what their drug will do.”

In a 2016 interview with The New York Times, Dr. Pazdur said that his views on cancer drug approvals have evolved with time. He described himself as being “on a jihad to streamline the review process and get things out the door faster.”

“I have evolved from regulator to regulator-advocate,” Dr. Pazdur told the newspaper.

His attitude reflected his personal experience in losing his wife to ovarian cancer in 2015, as well as shifts in science and law. In 2012, Congress passed a law that gave the FDA new resources to speed medicines for life-threatening diseases to market. In addition, advances in genetics appeared to be making some medications more effective and easier to test, Dr. Pazdur said in The New York Times interview.
 

Withdrawals seen as sign of success

Since the program’s inception, only 6% of accelerated approvals for oncology indications have been withdrawn, the FDA said.

It would be a sign that the program is working if the April meetings lead to further withdrawals of indications that have been granted accelerated approval, Julie R. Gralow, MD, chief medical officer of the American Society of Clinical Oncology, said in an interview with this news organization.

“It shouldn’t be seen as a failure,” Dr. Gralow said.

In her own practice at the Fred Hutchinson Cancer Research Center, Seattle, she has seen the value of emerging therapies for patients fighting advanced cancers. During her 25 years of clinical practice in an academic setting, she has gained access to drugs through single-patient investigative new drug applications.

However, this path is not an option for many patients who undergo treatment in facilities other than academic centers, she commented. She noted that the accelerated approval process is a way to expand access to emerging medicines, but she sees a need for caution in the use of drugs that have been given only this conditional approval. She emphasizes that such drugs may be suitable only for certain patients.

“I would say that, for metastatic patients, patients with incurable disease, we are willing to take some risk,” Dr. Gralow said. “We don’t have other options. They can’t wait the years that it would take to get a drug approved.”

One such patient is David Mitchell, who serves as the consumer representative on ODAC. He told this news organization that he is taking three drugs for multiple myeloma that received accelerated approvals: pomalidomide, bortezomib, and daratumumab.

“I want the FDA to have the option to approve drugs in an accelerated pathway, because as a patient taking three drugs granted accelerated approval, I’m benefiting – I’ve lived the benefit,” Mr. Mitchell said, “and I want other patients to have the opportunity to have that benefit.”

He believes that the FDA’s approach regarding accelerated approvals serves to get potentially beneficial medicines to patients who have few options and also fulfills the FDA’s mandate to protect the public from treatments that have little benefit but can cause harm.

Accelerated approval also offers needed flexibility to drugmakers as they develop more specifically targeted drugs for diseases that affect relatively few people, such as multiple myeloma, he said. “As the targeting of your therapies gets tighter and for smaller groups of patients, you have a harder time following the traditional model,” such as conducting large, double-blind, placebo-controlled trials that may indicate increased overall survival, he said.

“To me, this is the way the FDA intended it to work,” he added. “It’s going to offer the accelerated approval based on a surrogate endpoint for a safe drug, but it’s going to require the confirmatory trial, and if the confirmatory trial fails, it will pull the drug off the market.”

Some medicines that have received accelerated approvals may ultimately be found not to benefit patients, Mr. Mitchell acknowledged. But people in his situation, whose disease has progressed despite treatments, may want to take that risk, he added.


 

Four cancer indications recently withdrawn voluntarily by the manufacturer

• December 2020: Nivolumab for the treatment of patients with metastatic small cell lung cancer with progression after platinum-based chemotherapy and at least one other line of therapy (Bristol Myers Squibb).
• February 2021: Durvalumab for the treatment of patients with locally advanced or metastatic urothelial carcinoma whose disease has progressed during or following platinum-based chemotherapy or within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy (AstraZeneca).
• March 2021: Pembrolizumab for the treatment of patients with metastatic small cell lung cancer with disease progression on or after platinum-based chemotherapy and at least one other prior line of therapy (Merck).
• March 2021: Atezolizumab for treatment of patients with locally advanced or metastatic urothelial carcinoma who experience disease progression during or following platinum-containing atezolizumab chemotherapy or disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy (Genentech).

Six cancer indications under review at the April 2021 ODAC meeting

• Atezolizumab indicated in combination with protein-bound  for the treatment of adults with unresectable locally advanced or metastatic triple-negative  whose tumors express PD-L1 (PD-L1 stained tumor-infiltrating immune cells of any intensity covering ≥1% of the tumor area), as determined by an FDA-approved test.
• Atezolizumab indicated for patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing chemotherapy.
• Pembrolizumab indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing chemotherapy.
• Pembrolizumab indicated for the treatment of patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma whose tumors express PD-L1 (Combined Positive Score ≥1), as determined by an FDA-approved test, with disease progression on or after two or more prior lines of therapy including fluoropyrimidine- and platinum-containing chemotherapy and if appropriate, HER2/neu-targeted therapy.
• Pembrolizumab indicated for the treatment of patients with  who have been previously treated with .
• Nivolumab indicated as a single agent for the treatment of patients with hepatocellular carcinoma who have been previously treated with sorafenib.

A version of this article first appeared on Medscape.com.

U.S. regulators are stepping up scrutiny of therapies that were granted an accelerated approval to treat cancers on the basis of surrogate endpoints but have failed to show clinical or survival benefits upon more extensive testing.

At issue are a number of cancer indications for immunotherapies. Four have already been withdrawn (voluntarily by the manufacturer), and six more will be reviewed at an upcoming meeting.

In recent years, the US Food and Drug Administration has granted accelerated approvals to oncology medicines on the basis of evidence that suggests a benefit for patients. Examples of such evidence relate to response rates and estimates of tumor shrinkage. But these approvals are granted on the condition that the manufacturer conducts larger clinical trials that show clinical benefit, including benefit in overall survival.

Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence, has argued that the point of these conditional approvals is to find acceptable surrogate markers to allow people with “desperate illnesses” to have access to potentially helpful drugs while work continues to determine the drug’s actual benefit to patients.

Oncologists are now questioning whether the FDA has become too lenient in its approach, Daniel A. Goldstein, MD, a senior physician in medical oncology and internal medicine at the Rabin Medical Center, Petah Tikva, Israel, told this news organization.

“The main two things you want from a cancer drug is to live longer and live a higher quality of life,” said Goldstein. “But these endpoints that they’ve been using over the past few years are not really giving us confidence that these drugs are actually going to help to live longer or better.”

Dr. Pazdur said the FDA will consider withdrawing its accelerated approvals when results of further studies do not confirm expected benefit for patients.

“This is like the pendulum has swung as far as it was going to swing and now is on the backswing,” said Dr. Goldstein, also of the department of health policy and management at the University of North Carolina at Chapel Hill. “You could call this a watershed moment.”

Although there’s near universal interest in allowing people with advanced cancer access to promising medicines, there’s also rising concern about exposing patients needlessly to costly drugs with potentially tough side effects. That may prompt a shift in the standards U.S. regulators apply to cancer medicines, Dr. Goldstein said.
 

Indications withdrawn and under review

In a meeting scheduled for April 27-29, the FDA’s Oncologic Drugs Advisory Committee will review indications granted through the accelerated approval process for three immunotherapies: pembrolizumab (Keytruda), atezolizumab (Tecentriq), and nivolumab (Opdivo).

It is part of an industry-wide evaluation of accelerated approvals for cancer indications in which confirmatory trials did not confirm clinical benefit, the FDA noted.

The process has already led to voluntary withdrawals of four cancer indications by the manufacturers, including one indication each for pembrolizumab, atezolizumab, and nivolumab, and one for durvalumab (Imfinzi).

All of these immunotherapies are approved for numerous cancer indications, and they all remain on the market. It is only the U.S. approvals for particular cancer indications that have been withdrawn.

In the past, olaratumab (Lartruvo) was withdrawn from the market altogether. The FDA granted accelerated approval of the drug for soft tissue sarcoma, but clinical benefit was not confirmed in a phase 3 trial.
 

Issue highlighted by Dr. Prasad and Dr. Gyawali

In recent years, much of the attention on accelerated approvals was spurred by the work of a few researchers, particularly Vinay Prasad, MD, MPH, associate professor in the department of epidemiology and biostatistics, University of California, San Francisco, and Bishal Gyawali, MD, PhD, from Queen’s University Cancer Research Institute, Kingston, Ont. (Both are regular contributors to the oncology section of this news organization.)

Dr. Goldstein made this point in a tweet about the FDA’s announcement of the April ODAC meetings:

“Well done to @oncology_bg and @VPrasadMDMPH among others for highlighting in their papers that the FDA wasn’t properly evaluating accelerated approval drugs.

FDA have listened.

And I thought that the impact of academia was limited!”

Dr. Prasad has made the case for closer scrutiny of accelerated approvals in a number of journal articles and in his 2020 book, “Malignant: How Bad Policy and Bad Evidence Harm People with Cancer,” published by Johns Hopkins University Press.

The book includes highlights of a 2016 article published in Mayo Clinic Proceedings that focused on surrogate endpoints used for FDA approvals. In the article, Dr. Prasad and his coauthor report that they did not find formal analyses of the strength of the surrogate-survival correlation in 14 of 25 cases of accelerated approvals (56%) and in 11 of 30 traditional approvals (37%).

“Our results were concerning. They imply that many surrogates are based on little more than a gut feeling. You might rationalize that and argue a gut feeling is the same as ‘reasonably likely to predict,’ but no reasonable person could think a gut feeling means established,” Dr. Prasad writes in his book. “Our result suggests the FDA is using surrogate endpoints far beyond what may be fair or reasonable.”

Dr. Gyawali has argued that the process by which the FDA assesses cancer drugs for approvals has undergone a profound shift. He has most recently remarked on this in an October 2020 commentary on Medscape.

“Until the recent floodgate of approvals based on response rates from single-arm trials, the majority of cancer therapy decisions were supported by evidence generated from randomized controlled trials (RCTs),” Dr. Gyawali wrote. “The evidence base to support clinical decisions in managing therapeutic side effects has been comparatively sparse.”
 

Accelerated approval to improve access

The FDA has struggled for about 2 decades with questions of where to set the bar on evidence for promising cancer drugs.

The agency’s accelerated approval program for drugs began in 1992. During the first decade, the focus was largely on medicines related to HIV.

In the early 2000s, oncology drugs began to dominate the program.

Dr. Pazdur has presided over the FDA’s marked changes regarding the use of surrogate markers when weighing whether to allow sales of cancer medicines. Formerly a professor at the University of Texas MD Anderson Cancer Center, Houston, Dr. Pazdur joined the FDA as director of the Division of Oncology Drug Products in 1999.

Soon after his appointment, he had to field inquiries from pharmaceutical companies about how much evidence they needed to receive accelerated approvals.

Early on, he publicly expressed impatience about the drugmakers’ approach. “The purpose of accelerated approval was not accelerated drug company profits,” Dr. Padzur said at a 2004 ODAC meeting.

Rather, the point is to allow access to potentially helpful drugs while work continues to determine their actual benefit to patients, he explained.

“It wasn’t a license to do less, less, less, and less to a point now that we may be getting companies that are coming in” intent on determining the minimum evidence the FDA will take, Dr. Pazdur said. “It shouldn’t be what is the lowest. It is what is a sufficient amount to give patients and physicians a real understanding of what their drug will do.”

In a 2016 interview with The New York Times, Dr. Pazdur said that his views on cancer drug approvals have evolved with time. He described himself as being “on a jihad to streamline the review process and get things out the door faster.”

“I have evolved from regulator to regulator-advocate,” Dr. Pazdur told the newspaper.

His attitude reflected his personal experience in losing his wife to ovarian cancer in 2015, as well as shifts in science and law. In 2012, Congress passed a law that gave the FDA new resources to speed medicines for life-threatening diseases to market. In addition, advances in genetics appeared to be making some medications more effective and easier to test, Dr. Pazdur said in The New York Times interview.
 

Withdrawals seen as sign of success

Since the program’s inception, only 6% of accelerated approvals for oncology indications have been withdrawn, the FDA said.

It would be a sign that the program is working if the April meetings lead to further withdrawals of indications that have been granted accelerated approval, Julie R. Gralow, MD, chief medical officer of the American Society of Clinical Oncology, said in an interview with this news organization.

“It shouldn’t be seen as a failure,” Dr. Gralow said.

In her own practice at the Fred Hutchinson Cancer Research Center, Seattle, she has seen the value of emerging therapies for patients fighting advanced cancers. During her 25 years of clinical practice in an academic setting, she has gained access to drugs through single-patient investigative new drug applications.

However, this path is not an option for many patients who undergo treatment in facilities other than academic centers, she commented. She noted that the accelerated approval process is a way to expand access to emerging medicines, but she sees a need for caution in the use of drugs that have been given only this conditional approval. She emphasizes that such drugs may be suitable only for certain patients.

“I would say that, for metastatic patients, patients with incurable disease, we are willing to take some risk,” Dr. Gralow said. “We don’t have other options. They can’t wait the years that it would take to get a drug approved.”

One such patient is David Mitchell, who serves as the consumer representative on ODAC. He told this news organization that he is taking three drugs for multiple myeloma that received accelerated approvals: pomalidomide, bortezomib, and daratumumab.

“I want the FDA to have the option to approve drugs in an accelerated pathway, because as a patient taking three drugs granted accelerated approval, I’m benefiting – I’ve lived the benefit,” Mr. Mitchell said, “and I want other patients to have the opportunity to have that benefit.”

He believes that the FDA’s approach regarding accelerated approvals serves to get potentially beneficial medicines to patients who have few options and also fulfills the FDA’s mandate to protect the public from treatments that have little benefit but can cause harm.

Accelerated approval also offers needed flexibility to drugmakers as they develop more specifically targeted drugs for diseases that affect relatively few people, such as multiple myeloma, he said. “As the targeting of your therapies gets tighter and for smaller groups of patients, you have a harder time following the traditional model,” such as conducting large, double-blind, placebo-controlled trials that may indicate increased overall survival, he said.

“To me, this is the way the FDA intended it to work,” he added. “It’s going to offer the accelerated approval based on a surrogate endpoint for a safe drug, but it’s going to require the confirmatory trial, and if the confirmatory trial fails, it will pull the drug off the market.”

Some medicines that have received accelerated approvals may ultimately be found not to benefit patients, Mr. Mitchell acknowledged. But people in his situation, whose disease has progressed despite treatments, may want to take that risk, he added.


 

Four cancer indications recently withdrawn voluntarily by the manufacturer

• December 2020: Nivolumab for the treatment of patients with metastatic small cell lung cancer with progression after platinum-based chemotherapy and at least one other line of therapy (Bristol Myers Squibb).
• February 2021: Durvalumab for the treatment of patients with locally advanced or metastatic urothelial carcinoma whose disease has progressed during or following platinum-based chemotherapy or within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy (AstraZeneca).
• March 2021: Pembrolizumab for the treatment of patients with metastatic small cell lung cancer with disease progression on or after platinum-based chemotherapy and at least one other prior line of therapy (Merck).
• March 2021: Atezolizumab for treatment of patients with locally advanced or metastatic urothelial carcinoma who experience disease progression during or following platinum-containing atezolizumab chemotherapy or disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy (Genentech).

Six cancer indications under review at the April 2021 ODAC meeting

• Atezolizumab indicated in combination with protein-bound  for the treatment of adults with unresectable locally advanced or metastatic triple-negative  whose tumors express PD-L1 (PD-L1 stained tumor-infiltrating immune cells of any intensity covering ≥1% of the tumor area), as determined by an FDA-approved test.
• Atezolizumab indicated for patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing chemotherapy.
• Pembrolizumab indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing chemotherapy.
• Pembrolizumab indicated for the treatment of patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma whose tumors express PD-L1 (Combined Positive Score ≥1), as determined by an FDA-approved test, with disease progression on or after two or more prior lines of therapy including fluoropyrimidine- and platinum-containing chemotherapy and if appropriate, HER2/neu-targeted therapy.
• Pembrolizumab indicated for the treatment of patients with  who have been previously treated with .
• Nivolumab indicated as a single agent for the treatment of patients with hepatocellular carcinoma who have been previously treated with sorafenib.

A version of this article first appeared on Medscape.com.

How many epidemics can one country contain? Nearly all of our national attention has been focused on the COVID-19 epidemic but, lest we forget, there’s still another one to be reckoned with: the HIV epidemic is still going strong. In fact, it’s gathering strength, in part, because of the economic and health devastation wrought by COVID.

                Over nearly 4 decades, the epidemiology of HIV has changed, according to The Lancet’s HIV in the USA series. Current data, the report says, “illustrate an epidemic defined by stark health inequities that largely fall along lines of disadvantages in economic opportunity and social capital.” Moreover, the US, the authors say, “continues to lag behind other G-7 nations when it comes to controlling its HIV epidemic and is the only high-income country among the top 10 countries most affected by HIV.”

                The 6-paper series’ release comes 2 years after the launch of the US Department of Health and Human Services’ (HHS) announcement of its goal to reduce HIV transmissions by at least 90% by 2030.

                The authors analyzed publicly available HIV surveillance and census data to describe current prevalence and new HIV diagnoses by region, race, ethnicity, and age, as well as trends in those categories over time. They also reviewed literature to “explore the reasons” for the distribution of cases and important disparities in prevalence. Among other things, the researchers found “pronounced” racial, sexual, and gender disparities, “substantial” gaps in domestic program funding, and a “patchwork healthcare system” that limited access to treatment and prevention services.

                Although when it began, the HIV epidemic was focused largely on the bicoastal big cities, mainly New York and San Francisco, in recent years the South has been hit particularly hard, with 52% of new HIV transmissions in 2018, despite representing only 37% of the US population. Six Southern states (Florida, Georgia, Louisiana, Maryland, Mississippi, and Tennessee) and the District of Columbia had the highest annual HIV diagnosis rates between 2010 and 2018, likely reflecting the higher burden of infection among black residents: In 2018, 38% of all new HIV diagnoses among men who have sex with men (MSM) were in the black population, and 63% of those were in the South.

                The South’s HIV problem is intensified by disparities, the report says, that are probably driven by the restricted expansion of Medicaid, health care provider shortages, low health literacy, and stigma. The South also has the lowest number of pre-exposure prophylaxis (PrEP) users per new HIV diagnosis, in part because of the longer distances to PrEP services relative to other regions. More than half of MSM who live at least 60 minutes away from PrEP services live in the South. While HIV in the rural South largely is due to sexual transmission, the researchers note, the largest clusters of the concurrent opioid epidemic have been detected in rural and periurban counties of West Virginia and Indiana.

                Identifying HIV transmission clusters and outbreaks has traditionally been challenging for several reasons, the researchers say, including delays between infection and diagnosis, mobility of populations, and limitations in tracing sex and drug partners. They suggest that analysis of molecular data can help overcome some of those barriers, making it possible to identify clusters of ongoing HIV transmission.

                The report also recommends other approaches to better understand and respond to ongoing HIV infections, such as mapping and data visualization, telemedicine, and automated data systems to facilitate linkage to care. However, the authors add, gaps in data and data systems remain that prevent full understanding of some key impacts of the epidemic. But any interventions to promote HIV prevention and treatment adherence, the authors suggested, should take a multifaceted approach and address the whole individual.

                Chris Beyrer, MD, MPH, investigator at the Johns Hopkins Bloomberg School of Public Health, Baltimore, and a lead author on the series, says, “We have incredible tools to prevent and treat HIV, but people may not fully utilize them if they are facing personal or structural issues that pose more immediate hardship, like substance use and mental health disorders. You may struggle to take a daily medication if you are facing food insecurity or cannot find affordable treatment for your substance use disorder.”

                Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, and now also Chief Medical Advisor to President Biden, says, “To end the HIV epidemic, we must continue to develop and deploy novel HIV treatment and prevention strategies suited to the different needs and preferences of diverse populations disproportionately affected by HIV. It is also essential that HIV health services continue during the COVID-19 pandemic.”

How many epidemics can one country contain? Nearly all of our national attention has been focused on the COVID-19 epidemic but, lest we forget, there’s still another one to be reckoned with: the HIV epidemic is still going strong. In fact, it’s gathering strength, in part, because of the economic and health devastation wrought by COVID.

                Over nearly 4 decades, the epidemiology of HIV has changed, according to The Lancet’s HIV in the USA series. Current data, the report says, “illustrate an epidemic defined by stark health inequities that largely fall along lines of disadvantages in economic opportunity and social capital.” Moreover, the US, the authors say, “continues to lag behind other G-7 nations when it comes to controlling its HIV epidemic and is the only high-income country among the top 10 countries most affected by HIV.”

                The 6-paper series’ release comes 2 years after the launch of the US Department of Health and Human Services’ (HHS) announcement of its goal to reduce HIV transmissions by at least 90% by 2030.

                The authors analyzed publicly available HIV surveillance and census data to describe current prevalence and new HIV diagnoses by region, race, ethnicity, and age, as well as trends in those categories over time. They also reviewed literature to “explore the reasons” for the distribution of cases and important disparities in prevalence. Among other things, the researchers found “pronounced” racial, sexual, and gender disparities, “substantial” gaps in domestic program funding, and a “patchwork healthcare system” that limited access to treatment and prevention services.

                Although when it began, the HIV epidemic was focused largely on the bicoastal big cities, mainly New York and San Francisco, in recent years the South has been hit particularly hard, with 52% of new HIV transmissions in 2018, despite representing only 37% of the US population. Six Southern states (Florida, Georgia, Louisiana, Maryland, Mississippi, and Tennessee) and the District of Columbia had the highest annual HIV diagnosis rates between 2010 and 2018, likely reflecting the higher burden of infection among black residents: In 2018, 38% of all new HIV diagnoses among men who have sex with men (MSM) were in the black population, and 63% of those were in the South.

                The South’s HIV problem is intensified by disparities, the report says, that are probably driven by the restricted expansion of Medicaid, health care provider shortages, low health literacy, and stigma. The South also has the lowest number of pre-exposure prophylaxis (PrEP) users per new HIV diagnosis, in part because of the longer distances to PrEP services relative to other regions. More than half of MSM who live at least 60 minutes away from PrEP services live in the South. While HIV in the rural South largely is due to sexual transmission, the researchers note, the largest clusters of the concurrent opioid epidemic have been detected in rural and periurban counties of West Virginia and Indiana.

                Identifying HIV transmission clusters and outbreaks has traditionally been challenging for several reasons, the researchers say, including delays between infection and diagnosis, mobility of populations, and limitations in tracing sex and drug partners. They suggest that analysis of molecular data can help overcome some of those barriers, making it possible to identify clusters of ongoing HIV transmission.

                The report also recommends other approaches to better understand and respond to ongoing HIV infections, such as mapping and data visualization, telemedicine, and automated data systems to facilitate linkage to care. However, the authors add, gaps in data and data systems remain that prevent full understanding of some key impacts of the epidemic. But any interventions to promote HIV prevention and treatment adherence, the authors suggested, should take a multifaceted approach and address the whole individual.

                Chris Beyrer, MD, MPH, investigator at the Johns Hopkins Bloomberg School of Public Health, Baltimore, and a lead author on the series, says, “We have incredible tools to prevent and treat HIV, but people may not fully utilize them if they are facing personal or structural issues that pose more immediate hardship, like substance use and mental health disorders. You may struggle to take a daily medication if you are facing food insecurity or cannot find affordable treatment for your substance use disorder.”

                Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, and now also Chief Medical Advisor to President Biden, says, “To end the HIV epidemic, we must continue to develop and deploy novel HIV treatment and prevention strategies suited to the different needs and preferences of diverse populations disproportionately affected by HIV. It is also essential that HIV health services continue during the COVID-19 pandemic.”

How many epidemics can one country contain? Nearly all of our national attention has been focused on the COVID-19 epidemic but, lest we forget, there’s still another one to be reckoned with: the HIV epidemic is still going strong. In fact, it’s gathering strength, in part, because of the economic and health devastation wrought by COVID.

                Over nearly 4 decades, the epidemiology of HIV has changed, according to The Lancet’s HIV in the USA series. Current data, the report says, “illustrate an epidemic defined by stark health inequities that largely fall along lines of disadvantages in economic opportunity and social capital.” Moreover, the US, the authors say, “continues to lag behind other G-7 nations when it comes to controlling its HIV epidemic and is the only high-income country among the top 10 countries most affected by HIV.”

                The 6-paper series’ release comes 2 years after the launch of the US Department of Health and Human Services’ (HHS) announcement of its goal to reduce HIV transmissions by at least 90% by 2030.

                The authors analyzed publicly available HIV surveillance and census data to describe current prevalence and new HIV diagnoses by region, race, ethnicity, and age, as well as trends in those categories over time. They also reviewed literature to “explore the reasons” for the distribution of cases and important disparities in prevalence. Among other things, the researchers found “pronounced” racial, sexual, and gender disparities, “substantial” gaps in domestic program funding, and a “patchwork healthcare system” that limited access to treatment and prevention services.

                Although when it began, the HIV epidemic was focused largely on the bicoastal big cities, mainly New York and San Francisco, in recent years the South has been hit particularly hard, with 52% of new HIV transmissions in 2018, despite representing only 37% of the US population. Six Southern states (Florida, Georgia, Louisiana, Maryland, Mississippi, and Tennessee) and the District of Columbia had the highest annual HIV diagnosis rates between 2010 and 2018, likely reflecting the higher burden of infection among black residents: In 2018, 38% of all new HIV diagnoses among men who have sex with men (MSM) were in the black population, and 63% of those were in the South.

                The South’s HIV problem is intensified by disparities, the report says, that are probably driven by the restricted expansion of Medicaid, health care provider shortages, low health literacy, and stigma. The South also has the lowest number of pre-exposure prophylaxis (PrEP) users per new HIV diagnosis, in part because of the longer distances to PrEP services relative to other regions. More than half of MSM who live at least 60 minutes away from PrEP services live in the South. While HIV in the rural South largely is due to sexual transmission, the researchers note, the largest clusters of the concurrent opioid epidemic have been detected in rural and periurban counties of West Virginia and Indiana.

                Identifying HIV transmission clusters and outbreaks has traditionally been challenging for several reasons, the researchers say, including delays between infection and diagnosis, mobility of populations, and limitations in tracing sex and drug partners. They suggest that analysis of molecular data can help overcome some of those barriers, making it possible to identify clusters of ongoing HIV transmission.

                The report also recommends other approaches to better understand and respond to ongoing HIV infections, such as mapping and data visualization, telemedicine, and automated data systems to facilitate linkage to care. However, the authors add, gaps in data and data systems remain that prevent full understanding of some key impacts of the epidemic. But any interventions to promote HIV prevention and treatment adherence, the authors suggested, should take a multifaceted approach and address the whole individual.

                Chris Beyrer, MD, MPH, investigator at the Johns Hopkins Bloomberg School of Public Health, Baltimore, and a lead author on the series, says, “We have incredible tools to prevent and treat HIV, but people may not fully utilize them if they are facing personal or structural issues that pose more immediate hardship, like substance use and mental health disorders. You may struggle to take a daily medication if you are facing food insecurity or cannot find affordable treatment for your substance use disorder.”

                Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, and now also Chief Medical Advisor to President Biden, says, “To end the HIV epidemic, we must continue to develop and deploy novel HIV treatment and prevention strategies suited to the different needs and preferences of diverse populations disproportionately affected by HIV. It is also essential that HIV health services continue during the COVID-19 pandemic.”