Pertuzumab has a durable benefit in patients with metastatic HER2-positive breast cancer when added to trastuzumab and docetaxel as first-line therapy, with nearly 40% of patients achieving long-term survival, the CLEOPATRA end-of-study analysis shows.

The regimen, combining dual HER2 targeting with chemotherapy, became standard of care in this population as a result of its good efficacy and safety relative to placebo, first established in the phase 3, randomized trial 8 years ago (N Engl J Med. 2012;366:109-19).

Trial updates since then, most recently at a median follow-up of 50 months (N Engl J Med. 2015;372:724-34), have shown clear progression-free and overall survival benefits, with acceptable cardiac and other toxicity.

Investigators led by Sandra M. Swain, MD, of Georgetown University, Washington, performed a final analysis of data from the 808 patients in CLEOPATRA, now at a median follow-up of 99.9 months.

Results reported in The Lancet Oncology showed that, compared with placebo, pertuzumab prolonged investigator-assessed progression-free survival by 6.3 months (the same as that seen in the previous update) and prolonged overall survival by 16.3 months (up from 15.7 months in the previous update).

At 8 years, 37% of patients in the pertuzumab group were still alive, and 16% were still alive without progression.

“The combination of pertuzumab, trastuzumab, and docetaxel remains the standard of care for the first-line treatment of HER2-positive metastatic breast cancer, owing to its overall survival benefits and maintained long-term overall and cardiac safety,” Dr. Swain and coinvestigators concluded. “Prospective identification of patients who will be long-term responders to treatment is an area for future research.”

In an accompanying comment, Matteo Lambertini, MD, PhD, of IRCCS Ospedale Policlinico San Martino in Genova, Italy, and Ines Vaz-Luis, MD, of Institut Gustave Roussy in Villejuif, France, contended that these results, “which are also observed in real-world datasets, challenge the concept of HER2-positive metastatic breast cancer being an incurable disease and open the path to several interconnected clinical and research questions.”

Those questions include the optimal duration of anti-HER2 maintenance therapy in patients without disease progression, best strategies for combining this systemic therapy with local treatment to further improve survival, and new markers to better identify patients likely to be long-term responders, who might benefit from a curative approach, the authors elaborated. They noted that more than half of CLEOPATRA patients had de novo stage IV disease.

“The performance of the current standard pertuzumab-based first-line treatment in patients previously exposed to adjuvant or neoadjuvant anti-HER2 therapy remains to be clarified,” the authors wrote. “Results from several ongoing prospective cohort studies investigating real-world patterns of care and outcomes of patients with HER2-positive metastatic breast cancer will help to clarify this important issue and optimize treatment sequencing.”
 

Study details

The end-of-study analysis showed that median progression-free survival was 18.7 months with pertuzumab and 12.4 months with placebo (hazard ratio, 0.69; 95% confidence interval, 0.59-0.81). The 8-year landmark progression-free survival rate was 16% with the former and 10% with the latter.

The median overall survival was 57.1 months with pertuzumab and 40.8 months with placebo (HR, 0.69; 95% CI, 0.58-0.82). The 8-year landmark overall survival rate was 37% with the former and 23% with the latter.

A comparison of patients who did and did not achieve long-term response showed that, in both treatment groups, the former more often had tumors that were 3+ positive by HER2 immunohistochemistry and PIK3CA wild-type tumors. The leading grade 3 or 4 adverse event was neutropenia, seen in 49% of patients in the pertuzumab group and 46% of those in the placebo group. The rate of treatment-related death was 1% and 2%, respectively.

Since the last update, only two additional serious adverse events were reported: one case of heart failure and one case of symptomatic left ventricular systolic dysfunction in patients given pertuzumab.

The CLEOPATRA trial was funded by F. Hoffmann-La Roche and Genentech. Dr. Swain and coauthors disclosed relationships with these and other companies. Dr. Lambertini disclosed relationships with Roche, Theramex, and Takeda. Dr. Vaz-Luis disclosed relationships with AstraZeneca, Kephren, and Novartis.

SOURCE: Swain SM et al. Lancet Oncol. 2020 Mar 12. doi: 10.1016/S1470-2045(19)30863-0; Lambertini M et al. Lancet Oncol. 2020 Mar 12. doi: 10.1016/S1470-2045(20)30058-9.

Pertuzumab has a durable benefit in patients with metastatic HER2-positive breast cancer when added to trastuzumab and docetaxel as first-line therapy, with nearly 40% of patients achieving long-term survival, the CLEOPATRA end-of-study analysis shows.

The regimen, combining dual HER2 targeting with chemotherapy, became standard of care in this population as a result of its good efficacy and safety relative to placebo, first established in the phase 3, randomized trial 8 years ago (N Engl J Med. 2012;366:109-19).

Trial updates since then, most recently at a median follow-up of 50 months (N Engl J Med. 2015;372:724-34), have shown clear progression-free and overall survival benefits, with acceptable cardiac and other toxicity.

Investigators led by Sandra M. Swain, MD, of Georgetown University, Washington, performed a final analysis of data from the 808 patients in CLEOPATRA, now at a median follow-up of 99.9 months.

Results reported in The Lancet Oncology showed that, compared with placebo, pertuzumab prolonged investigator-assessed progression-free survival by 6.3 months (the same as that seen in the previous update) and prolonged overall survival by 16.3 months (up from 15.7 months in the previous update).

At 8 years, 37% of patients in the pertuzumab group were still alive, and 16% were still alive without progression.

“The combination of pertuzumab, trastuzumab, and docetaxel remains the standard of care for the first-line treatment of HER2-positive metastatic breast cancer, owing to its overall survival benefits and maintained long-term overall and cardiac safety,” Dr. Swain and coinvestigators concluded. “Prospective identification of patients who will be long-term responders to treatment is an area for future research.”

In an accompanying comment, Matteo Lambertini, MD, PhD, of IRCCS Ospedale Policlinico San Martino in Genova, Italy, and Ines Vaz-Luis, MD, of Institut Gustave Roussy in Villejuif, France, contended that these results, “which are also observed in real-world datasets, challenge the concept of HER2-positive metastatic breast cancer being an incurable disease and open the path to several interconnected clinical and research questions.”

Those questions include the optimal duration of anti-HER2 maintenance therapy in patients without disease progression, best strategies for combining this systemic therapy with local treatment to further improve survival, and new markers to better identify patients likely to be long-term responders, who might benefit from a curative approach, the authors elaborated. They noted that more than half of CLEOPATRA patients had de novo stage IV disease.

“The performance of the current standard pertuzumab-based first-line treatment in patients previously exposed to adjuvant or neoadjuvant anti-HER2 therapy remains to be clarified,” the authors wrote. “Results from several ongoing prospective cohort studies investigating real-world patterns of care and outcomes of patients with HER2-positive metastatic breast cancer will help to clarify this important issue and optimize treatment sequencing.”
 

Study details

The end-of-study analysis showed that median progression-free survival was 18.7 months with pertuzumab and 12.4 months with placebo (hazard ratio, 0.69; 95% confidence interval, 0.59-0.81). The 8-year landmark progression-free survival rate was 16% with the former and 10% with the latter.

The median overall survival was 57.1 months with pertuzumab and 40.8 months with placebo (HR, 0.69; 95% CI, 0.58-0.82). The 8-year landmark overall survival rate was 37% with the former and 23% with the latter.

A comparison of patients who did and did not achieve long-term response showed that, in both treatment groups, the former more often had tumors that were 3+ positive by HER2 immunohistochemistry and PIK3CA wild-type tumors. The leading grade 3 or 4 adverse event was neutropenia, seen in 49% of patients in the pertuzumab group and 46% of those in the placebo group. The rate of treatment-related death was 1% and 2%, respectively.

Since the last update, only two additional serious adverse events were reported: one case of heart failure and one case of symptomatic left ventricular systolic dysfunction in patients given pertuzumab.

The CLEOPATRA trial was funded by F. Hoffmann-La Roche and Genentech. Dr. Swain and coauthors disclosed relationships with these and other companies. Dr. Lambertini disclosed relationships with Roche, Theramex, and Takeda. Dr. Vaz-Luis disclosed relationships with AstraZeneca, Kephren, and Novartis.

SOURCE: Swain SM et al. Lancet Oncol. 2020 Mar 12. doi: 10.1016/S1470-2045(19)30863-0; Lambertini M et al. Lancet Oncol. 2020 Mar 12. doi: 10.1016/S1470-2045(20)30058-9.

Pertuzumab has a durable benefit in patients with metastatic HER2-positive breast cancer when added to trastuzumab and docetaxel as first-line therapy, with nearly 40% of patients achieving long-term survival, the CLEOPATRA end-of-study analysis shows.

The regimen, combining dual HER2 targeting with chemotherapy, became standard of care in this population as a result of its good efficacy and safety relative to placebo, first established in the phase 3, randomized trial 8 years ago (N Engl J Med. 2012;366:109-19).

Trial updates since then, most recently at a median follow-up of 50 months (N Engl J Med. 2015;372:724-34), have shown clear progression-free and overall survival benefits, with acceptable cardiac and other toxicity.

Investigators led by Sandra M. Swain, MD, of Georgetown University, Washington, performed a final analysis of data from the 808 patients in CLEOPATRA, now at a median follow-up of 99.9 months.

Results reported in The Lancet Oncology showed that, compared with placebo, pertuzumab prolonged investigator-assessed progression-free survival by 6.3 months (the same as that seen in the previous update) and prolonged overall survival by 16.3 months (up from 15.7 months in the previous update).

At 8 years, 37% of patients in the pertuzumab group were still alive, and 16% were still alive without progression.

“The combination of pertuzumab, trastuzumab, and docetaxel remains the standard of care for the first-line treatment of HER2-positive metastatic breast cancer, owing to its overall survival benefits and maintained long-term overall and cardiac safety,” Dr. Swain and coinvestigators concluded. “Prospective identification of patients who will be long-term responders to treatment is an area for future research.”

In an accompanying comment, Matteo Lambertini, MD, PhD, of IRCCS Ospedale Policlinico San Martino in Genova, Italy, and Ines Vaz-Luis, MD, of Institut Gustave Roussy in Villejuif, France, contended that these results, “which are also observed in real-world datasets, challenge the concept of HER2-positive metastatic breast cancer being an incurable disease and open the path to several interconnected clinical and research questions.”

Those questions include the optimal duration of anti-HER2 maintenance therapy in patients without disease progression, best strategies for combining this systemic therapy with local treatment to further improve survival, and new markers to better identify patients likely to be long-term responders, who might benefit from a curative approach, the authors elaborated. They noted that more than half of CLEOPATRA patients had de novo stage IV disease.

“The performance of the current standard pertuzumab-based first-line treatment in patients previously exposed to adjuvant or neoadjuvant anti-HER2 therapy remains to be clarified,” the authors wrote. “Results from several ongoing prospective cohort studies investigating real-world patterns of care and outcomes of patients with HER2-positive metastatic breast cancer will help to clarify this important issue and optimize treatment sequencing.”
 

Study details

The end-of-study analysis showed that median progression-free survival was 18.7 months with pertuzumab and 12.4 months with placebo (hazard ratio, 0.69; 95% confidence interval, 0.59-0.81). The 8-year landmark progression-free survival rate was 16% with the former and 10% with the latter.

The median overall survival was 57.1 months with pertuzumab and 40.8 months with placebo (HR, 0.69; 95% CI, 0.58-0.82). The 8-year landmark overall survival rate was 37% with the former and 23% with the latter.

A comparison of patients who did and did not achieve long-term response showed that, in both treatment groups, the former more often had tumors that were 3+ positive by HER2 immunohistochemistry and PIK3CA wild-type tumors. The leading grade 3 or 4 adverse event was neutropenia, seen in 49% of patients in the pertuzumab group and 46% of those in the placebo group. The rate of treatment-related death was 1% and 2%, respectively.

Since the last update, only two additional serious adverse events were reported: one case of heart failure and one case of symptomatic left ventricular systolic dysfunction in patients given pertuzumab.

The CLEOPATRA trial was funded by F. Hoffmann-La Roche and Genentech. Dr. Swain and coauthors disclosed relationships with these and other companies. Dr. Lambertini disclosed relationships with Roche, Theramex, and Takeda. Dr. Vaz-Luis disclosed relationships with AstraZeneca, Kephren, and Novartis.

SOURCE: Swain SM et al. Lancet Oncol. 2020 Mar 12. doi: 10.1016/S1470-2045(19)30863-0; Lambertini M et al. Lancet Oncol. 2020 Mar 12. doi: 10.1016/S1470-2045(20)30058-9.

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The first data on myocardial injury linked with COVID-19 disease during the start of the pandemic in Wuhan, China serves as a “wake up call” for clinicians and the general public on what the United States and other Western countries can expect as the SARS-CoV-2 virus spreads and case numbers mount: a potentially “daunting” toll of deaths as an infection with a tendency to be most severe in patients with underlying cardiovascular disease hits populations that include large numbers of such patients.

“A consistent picture emerges” from two reports on a total of 603 COVID-19 patients treated at two academic hospitals in Wuhan, which described “remarkably similar characteristics of patients who develop myocardial injury” associated with their infection. “Patients who develop myocardial injury with COVID-19 have clinical evidence of higher acuity, with a higher incidence of acute respiratory distress syndrome and more frequent need for assisted ventilation than those without myocardial injury, and the patients who are more prone to have myocardial injury are “older patients with preexisting cardiovascular complications and diabetes,” Robert O. Bonow, MD, and coauthors wrote in an editorial published online (JAMA Cardiol. 2020 Mar 27. doi: 10.1001/jamacardio.2020.1105).

These new findings have special relevance to the United States and other Western countries because of their substantial numbers of elderly patients with cardiovascular diseases, said Dr. Bonow, professor of medicine at Northwestern University, Chicago, and coauthors.

One of the two reports cited in the editorial reviewed 416 patients hospitalized at Renmin Hospital in Wuhan during the period of Jan. 20 to Feb. 10, 2020, with confirmed COVID-19 disease, and found that 20% of the cohort had evidence of cardiac injury, defined as blood levels of the high-sensitivity troponin I cardiac biomarker above the 99th-percentile upper reference limit, regardless of new abnormalities in electrocardiography and echocardiography.

The analysis also showed that patients with myocardial injury had a significantly higher in-hospital mortality rate, 51%, compared with a 5% mortality rate among patients without myocardial injury, and among patients with myocardial injury those with elevated high-sensitivity troponin I had an even higher mortality rate (JAMA Cardiol. 2020 Mar 25. doi: 10.1001/jamacardio.2020.0950).

A second review of 187 confirmed COVID-19 cases at Seventh Hospital in Wuhan during the period of Jan. 23 to Feb. 23, 2020, showed similar findings, with a 28% prevalence of myocardial injury at admission based on an elevated level of plasma troponin T (TnT), and 35% had cardiovascular disease (CVD) including hypertension, coronary heart disease, and cardiomyopathy. Elevated TnT levels and CVD at entry each linked with substantially increased mortality. The incidence of death among patients with elevated TnT and no underlying CVD was 38% compared with 8% among patients without elevated TnT or underlying CVD. Among patients admitted with underlying CVD those who also had an elevated TnT had a 69% death rate during hospitalization compared with a 13% rate in those without TnT elevation (JAMA Cardiol. 2020 Mar 27. doi: 10.1001/jamacardio.2020.1017).

Dr. Bonow and coauthors noted that patients with chronic coronary artery disease have a heightened risk for developing acute coronary syndrome during acute infection, potentially resulting from a severe increase in myocardial demand during infection, or severe systemic inflammatory stress that could result in atherosclerotic plaque instability and rupture as well as vascular and myocardial inflammation.

In addition, patients with heart failure are prone to hemodynamic instability during severe infection. “Thus it is anticipated that patients with underlying cardiovascular diseases, which are more prevalent in older adults, would be susceptible to higher risks of adverse outcomes and death during the severe and aggressive inflammatory responses to COVID-19 than individuals who are younger and healthier,” they wrote.

They also cited the potential for acute or fulminant myocarditis as well as new-onset heart failure caused by the SARS-CoV-2 virus that causes COVID-19 disease based on experience with the related Middle East respiratory syndrome coronavirus. Another concerning observation is that the SARS-CoV-2 virus binds to the angiotensin-converting enzyme 2 protein on cell surfaces as its main entry receptor, “raising the possibility of direct viral infection of vascular endothelium and myocardium,” a process that itself could produce myocardial injury and myocarditis.

These new findings from COVID-19 patients in Wuhan represent early data from what has become a global pandemic, and raise questions about generalizability, but for the time being a key message from these early cases is that prevention of SARS-CoV-2 infection is paramount. “Until we know more, the populations described in these primary data reports should be most observant of strict hand hygiene, social distancing, and, where available, COVID-19 testing,” the authors said.

Dr. Bonow and coauthors had no disclosures.

[email protected]

The first data on myocardial injury linked with COVID-19 disease during the start of the pandemic in Wuhan, China serves as a “wake up call” for clinicians and the general public on what the United States and other Western countries can expect as the SARS-CoV-2 virus spreads and case numbers mount: a potentially “daunting” toll of deaths as an infection with a tendency to be most severe in patients with underlying cardiovascular disease hits populations that include large numbers of such patients.

“A consistent picture emerges” from two reports on a total of 603 COVID-19 patients treated at two academic hospitals in Wuhan, which described “remarkably similar characteristics of patients who develop myocardial injury” associated with their infection. “Patients who develop myocardial injury with COVID-19 have clinical evidence of higher acuity, with a higher incidence of acute respiratory distress syndrome and more frequent need for assisted ventilation than those without myocardial injury, and the patients who are more prone to have myocardial injury are “older patients with preexisting cardiovascular complications and diabetes,” Robert O. Bonow, MD, and coauthors wrote in an editorial published online (JAMA Cardiol. 2020 Mar 27. doi: 10.1001/jamacardio.2020.1105).

These new findings have special relevance to the United States and other Western countries because of their substantial numbers of elderly patients with cardiovascular diseases, said Dr. Bonow, professor of medicine at Northwestern University, Chicago, and coauthors.

One of the two reports cited in the editorial reviewed 416 patients hospitalized at Renmin Hospital in Wuhan during the period of Jan. 20 to Feb. 10, 2020, with confirmed COVID-19 disease, and found that 20% of the cohort had evidence of cardiac injury, defined as blood levels of the high-sensitivity troponin I cardiac biomarker above the 99th-percentile upper reference limit, regardless of new abnormalities in electrocardiography and echocardiography.

The analysis also showed that patients with myocardial injury had a significantly higher in-hospital mortality rate, 51%, compared with a 5% mortality rate among patients without myocardial injury, and among patients with myocardial injury those with elevated high-sensitivity troponin I had an even higher mortality rate (JAMA Cardiol. 2020 Mar 25. doi: 10.1001/jamacardio.2020.0950).

A second review of 187 confirmed COVID-19 cases at Seventh Hospital in Wuhan during the period of Jan. 23 to Feb. 23, 2020, showed similar findings, with a 28% prevalence of myocardial injury at admission based on an elevated level of plasma troponin T (TnT), and 35% had cardiovascular disease (CVD) including hypertension, coronary heart disease, and cardiomyopathy. Elevated TnT levels and CVD at entry each linked with substantially increased mortality. The incidence of death among patients with elevated TnT and no underlying CVD was 38% compared with 8% among patients without elevated TnT or underlying CVD. Among patients admitted with underlying CVD those who also had an elevated TnT had a 69% death rate during hospitalization compared with a 13% rate in those without TnT elevation (JAMA Cardiol. 2020 Mar 27. doi: 10.1001/jamacardio.2020.1017).

Dr. Bonow and coauthors noted that patients with chronic coronary artery disease have a heightened risk for developing acute coronary syndrome during acute infection, potentially resulting from a severe increase in myocardial demand during infection, or severe systemic inflammatory stress that could result in atherosclerotic plaque instability and rupture as well as vascular and myocardial inflammation.

In addition, patients with heart failure are prone to hemodynamic instability during severe infection. “Thus it is anticipated that patients with underlying cardiovascular diseases, which are more prevalent in older adults, would be susceptible to higher risks of adverse outcomes and death during the severe and aggressive inflammatory responses to COVID-19 than individuals who are younger and healthier,” they wrote.

They also cited the potential for acute or fulminant myocarditis as well as new-onset heart failure caused by the SARS-CoV-2 virus that causes COVID-19 disease based on experience with the related Middle East respiratory syndrome coronavirus. Another concerning observation is that the SARS-CoV-2 virus binds to the angiotensin-converting enzyme 2 protein on cell surfaces as its main entry receptor, “raising the possibility of direct viral infection of vascular endothelium and myocardium,” a process that itself could produce myocardial injury and myocarditis.

These new findings from COVID-19 patients in Wuhan represent early data from what has become a global pandemic, and raise questions about generalizability, but for the time being a key message from these early cases is that prevention of SARS-CoV-2 infection is paramount. “Until we know more, the populations described in these primary data reports should be most observant of strict hand hygiene, social distancing, and, where available, COVID-19 testing,” the authors said.

Dr. Bonow and coauthors had no disclosures.

[email protected]

The first data on myocardial injury linked with COVID-19 disease during the start of the pandemic in Wuhan, China serves as a “wake up call” for clinicians and the general public on what the United States and other Western countries can expect as the SARS-CoV-2 virus spreads and case numbers mount: a potentially “daunting” toll of deaths as an infection with a tendency to be most severe in patients with underlying cardiovascular disease hits populations that include large numbers of such patients.

“A consistent picture emerges” from two reports on a total of 603 COVID-19 patients treated at two academic hospitals in Wuhan, which described “remarkably similar characteristics of patients who develop myocardial injury” associated with their infection. “Patients who develop myocardial injury with COVID-19 have clinical evidence of higher acuity, with a higher incidence of acute respiratory distress syndrome and more frequent need for assisted ventilation than those without myocardial injury, and the patients who are more prone to have myocardial injury are “older patients with preexisting cardiovascular complications and diabetes,” Robert O. Bonow, MD, and coauthors wrote in an editorial published online (JAMA Cardiol. 2020 Mar 27. doi: 10.1001/jamacardio.2020.1105).

These new findings have special relevance to the United States and other Western countries because of their substantial numbers of elderly patients with cardiovascular diseases, said Dr. Bonow, professor of medicine at Northwestern University, Chicago, and coauthors.

One of the two reports cited in the editorial reviewed 416 patients hospitalized at Renmin Hospital in Wuhan during the period of Jan. 20 to Feb. 10, 2020, with confirmed COVID-19 disease, and found that 20% of the cohort had evidence of cardiac injury, defined as blood levels of the high-sensitivity troponin I cardiac biomarker above the 99th-percentile upper reference limit, regardless of new abnormalities in electrocardiography and echocardiography.

The analysis also showed that patients with myocardial injury had a significantly higher in-hospital mortality rate, 51%, compared with a 5% mortality rate among patients without myocardial injury, and among patients with myocardial injury those with elevated high-sensitivity troponin I had an even higher mortality rate (JAMA Cardiol. 2020 Mar 25. doi: 10.1001/jamacardio.2020.0950).

A second review of 187 confirmed COVID-19 cases at Seventh Hospital in Wuhan during the period of Jan. 23 to Feb. 23, 2020, showed similar findings, with a 28% prevalence of myocardial injury at admission based on an elevated level of plasma troponin T (TnT), and 35% had cardiovascular disease (CVD) including hypertension, coronary heart disease, and cardiomyopathy. Elevated TnT levels and CVD at entry each linked with substantially increased mortality. The incidence of death among patients with elevated TnT and no underlying CVD was 38% compared with 8% among patients without elevated TnT or underlying CVD. Among patients admitted with underlying CVD those who also had an elevated TnT had a 69% death rate during hospitalization compared with a 13% rate in those without TnT elevation (JAMA Cardiol. 2020 Mar 27. doi: 10.1001/jamacardio.2020.1017).

Dr. Bonow and coauthors noted that patients with chronic coronary artery disease have a heightened risk for developing acute coronary syndrome during acute infection, potentially resulting from a severe increase in myocardial demand during infection, or severe systemic inflammatory stress that could result in atherosclerotic plaque instability and rupture as well as vascular and myocardial inflammation.

In addition, patients with heart failure are prone to hemodynamic instability during severe infection. “Thus it is anticipated that patients with underlying cardiovascular diseases, which are more prevalent in older adults, would be susceptible to higher risks of adverse outcomes and death during the severe and aggressive inflammatory responses to COVID-19 than individuals who are younger and healthier,” they wrote.

They also cited the potential for acute or fulminant myocarditis as well as new-onset heart failure caused by the SARS-CoV-2 virus that causes COVID-19 disease based on experience with the related Middle East respiratory syndrome coronavirus. Another concerning observation is that the SARS-CoV-2 virus binds to the angiotensin-converting enzyme 2 protein on cell surfaces as its main entry receptor, “raising the possibility of direct viral infection of vascular endothelium and myocardium,” a process that itself could produce myocardial injury and myocarditis.

These new findings from COVID-19 patients in Wuhan represent early data from what has become a global pandemic, and raise questions about generalizability, but for the time being a key message from these early cases is that prevention of SARS-CoV-2 infection is paramount. “Until we know more, the populations described in these primary data reports should be most observant of strict hand hygiene, social distancing, and, where available, COVID-19 testing,” the authors said.

Dr. Bonow and coauthors had no disclosures.

[email protected]

Hyponatremia, defined as a plasma sodium concentration ≤ 135 mmol/L at admission, was associated with complications during episodes of acute pain from sickle cell disease, according to a large retrospective analysis.

The French study assessed 1,218 stays of 406 patients admitted for treatment of an acute painful episode of sickle cell disease between 2010-2015. The primary composite endpoint comprised acute chest syndrome, intensive care unit transfer, red blood cell transfusion or inpatient death. The analyses were adjusted for age, sex, hemoglobin genotype and concentration, LDH concentration, and white blood cell count, according to the researchers.

Hyponatremia at admission in the center was associated with the primary endpoint (adjusted odds ratio (OR) 1.95, P = .001). This association was independent from baseline demographic characteristics (age, sex, hemoglobin genotype) and from other prognostic factors examined in the study (lower hemoglobin concentration, higher white blood cell count and LDH concentration).

With regard to individual components of the primary endpoint, hyponatremia was associated with acute chest syndrome (OR 1.95, P = .008) and red blood cell transfusion (OR 2.71, P <.001), but not significantly with intensive care unit transfer (OR 1.83, P  = .074). In addition, the adjusted mean length of stay was significantly longer by 1.1 days (P < .001) in patients with hyponatremia at admission.

The study received no funding and the researchers reported that they had no conflicts of interest.

SOURCE: Rech JS et al. Amer J Med. 2020. doi.org/10.1016/j.amjmed.2020.02.017.

Hyponatremia, defined as a plasma sodium concentration ≤ 135 mmol/L at admission, was associated with complications during episodes of acute pain from sickle cell disease, according to a large retrospective analysis.

The French study assessed 1,218 stays of 406 patients admitted for treatment of an acute painful episode of sickle cell disease between 2010-2015. The primary composite endpoint comprised acute chest syndrome, intensive care unit transfer, red blood cell transfusion or inpatient death. The analyses were adjusted for age, sex, hemoglobin genotype and concentration, LDH concentration, and white blood cell count, according to the researchers.

Hyponatremia at admission in the center was associated with the primary endpoint (adjusted odds ratio (OR) 1.95, P = .001). This association was independent from baseline demographic characteristics (age, sex, hemoglobin genotype) and from other prognostic factors examined in the study (lower hemoglobin concentration, higher white blood cell count and LDH concentration).

With regard to individual components of the primary endpoint, hyponatremia was associated with acute chest syndrome (OR 1.95, P = .008) and red blood cell transfusion (OR 2.71, P <.001), but not significantly with intensive care unit transfer (OR 1.83, P  = .074). In addition, the adjusted mean length of stay was significantly longer by 1.1 days (P < .001) in patients with hyponatremia at admission.

The study received no funding and the researchers reported that they had no conflicts of interest.

SOURCE: Rech JS et al. Amer J Med. 2020. doi.org/10.1016/j.amjmed.2020.02.017.

Hyponatremia, defined as a plasma sodium concentration ≤ 135 mmol/L at admission, was associated with complications during episodes of acute pain from sickle cell disease, according to a large retrospective analysis.

The French study assessed 1,218 stays of 406 patients admitted for treatment of an acute painful episode of sickle cell disease between 2010-2015. The primary composite endpoint comprised acute chest syndrome, intensive care unit transfer, red blood cell transfusion or inpatient death. The analyses were adjusted for age, sex, hemoglobin genotype and concentration, LDH concentration, and white blood cell count, according to the researchers.

Hyponatremia at admission in the center was associated with the primary endpoint (adjusted odds ratio (OR) 1.95, P = .001). This association was independent from baseline demographic characteristics (age, sex, hemoglobin genotype) and from other prognostic factors examined in the study (lower hemoglobin concentration, higher white blood cell count and LDH concentration).

With regard to individual components of the primary endpoint, hyponatremia was associated with acute chest syndrome (OR 1.95, P = .008) and red blood cell transfusion (OR 2.71, P <.001), but not significantly with intensive care unit transfer (OR 1.83, P  = .074). In addition, the adjusted mean length of stay was significantly longer by 1.1 days (P < .001) in patients with hyponatremia at admission.

The study received no funding and the researchers reported that they had no conflicts of interest.

SOURCE: Rech JS et al. Amer J Med. 2020. doi.org/10.1016/j.amjmed.2020.02.017.

Current risk factors used to screen for hepatitis C should be updated, according to study results of 106,842 pregnant women who underwent screening.

Courtesy NIH

“Because risk-factor screening has obvious limitations, universal screening in pregnancy has been suggested to allow for linkage to postpartum care and identification of children for future testing and treatment,” wrote Mona Prasad, DO, of Ohio State University, Columbus, and colleagues.

In a study published in Obstetrics & Gynecology, the researchers reviewed data from women with singleton pregnancies presenting for prenatal care prior to 23 weeks’ gestation during 2012-2015. Of these, 254 tested positive for the hepatitis C virus (HCV) antibody, for a seroprevalence rate of 2.4 cases per 1,000 women.

The researchers conducted a case-control analysis of 131 women who tested positive and 251 controls to identify HCV infection risk factors based on interviews and chart reviews. They found that risk factors significantly associated with positive HCV antibodies included injection drug use (adjusted odds ratio, 22.9), a history of blood transfusion (aOR, 3.7), having an HCV-infected partner (aOR, 6.3), having had more than three sexual partners (aOR, 5.3), and smoking during pregnancy (aOR, 2.4).

In an unadjusted analysis, the researchers confirmed two of the risk factors currently recommended by the Centers for Disease Control and Prevention for screening for HCV: injection drug use and being born to a mother with HCV infection, but not dialysis, organ transplantation, or HIV infection.

“Our results demonstrate that current risk factors could be contemporized,” Dr. Prasad and colleagues noted. “The currently accepted risk factors such as exposure to clotting factors, dialysis, and organ transplants are unlikely to be found. A thorough assessment of injection drug use history, smoking, transfusions, number of sexual partners, and partners with HCV infection is more sensitive in an obstetric population.”

The study findings were limited by several factors including possible selection bias and inclusion of only 65% of eligible women who were HCV positive, as well as a lack of screening data from 2016 to the present, which may not reflect the impact of the recent opioid epidemic, the researchers noted. However, the results were strengthened by the large sample size, and the generalizability of the study population.

“Our results regarding prevalence rates and risk factors of HCV antibody among pregnant women in the United States will be valuable to policymakers as they weigh the costs and benefits of universal screening,” Dr. Prasad and associates concluded.

Although universal screening has the potential to be more cost effective, given the small population of pregnant women eligible for treatment and lack of an available treatment, “the rationale is weaker for unique universal HCV screening recommendations for pregnant women,” they said.

By contrast, Sammy Saab, MD, MPH, of the University of California, Los Angeles; Ravina Kullar, PharmD, MPH, of Gilead Sciences, Foster City, Calif.; and Prabhu Gounder, MD, MPH, of the Los Angeles Department of Public Health, wrote an accompanying commentary in favor of universal HCV screening for pregnant women, in part because of the increase in HCV in the younger population overall.

“For many women of reproductive age, pregnancy is one of their few points of contact with their health care provider; therefore, pregnancy could provide a crucial time for targeting this population,” they noted.

Risk-based screening is of limited effectiveness because patients are not identified by way of current screening tools or they decline to reveal risk factors that providers might miss, the editorialists said. Pregnancy has not been shown to affect the accuracy of HCV tests, and identifying infections in mothers allows for screening in children as well.

“The perinatal hepatitis B virus infection program, which has been implemented in several state and local public health departments, could serve as an example for how to conduct surveillance for mothers with HCV infection and to ensure that HCV-exposed children receive appropriate follow-up testing and linkage to care,” the editorialists concluded.

The study was supported in part by multiple grants from the National Institute of Child Health and Human Development. Dr. Prasad disclosed funding from Ohio State University and from Gilead. Coauthors had links with pharmaceutical companies, associations, and organizations – most unrelated to this study. The editorialists had no financial conflicts to disclose.

SOURCES: Prasad M et al. Obstet Gynecol. 2020;135:778-88; Saab S et al. Obstet Gynecol. 2020;135:773-7.

Current risk factors used to screen for hepatitis C should be updated, according to study results of 106,842 pregnant women who underwent screening.

Courtesy NIH

“Because risk-factor screening has obvious limitations, universal screening in pregnancy has been suggested to allow for linkage to postpartum care and identification of children for future testing and treatment,” wrote Mona Prasad, DO, of Ohio State University, Columbus, and colleagues.

In a study published in Obstetrics & Gynecology, the researchers reviewed data from women with singleton pregnancies presenting for prenatal care prior to 23 weeks’ gestation during 2012-2015. Of these, 254 tested positive for the hepatitis C virus (HCV) antibody, for a seroprevalence rate of 2.4 cases per 1,000 women.

The researchers conducted a case-control analysis of 131 women who tested positive and 251 controls to identify HCV infection risk factors based on interviews and chart reviews. They found that risk factors significantly associated with positive HCV antibodies included injection drug use (adjusted odds ratio, 22.9), a history of blood transfusion (aOR, 3.7), having an HCV-infected partner (aOR, 6.3), having had more than three sexual partners (aOR, 5.3), and smoking during pregnancy (aOR, 2.4).

In an unadjusted analysis, the researchers confirmed two of the risk factors currently recommended by the Centers for Disease Control and Prevention for screening for HCV: injection drug use and being born to a mother with HCV infection, but not dialysis, organ transplantation, or HIV infection.

“Our results demonstrate that current risk factors could be contemporized,” Dr. Prasad and colleagues noted. “The currently accepted risk factors such as exposure to clotting factors, dialysis, and organ transplants are unlikely to be found. A thorough assessment of injection drug use history, smoking, transfusions, number of sexual partners, and partners with HCV infection is more sensitive in an obstetric population.”

The study findings were limited by several factors including possible selection bias and inclusion of only 65% of eligible women who were HCV positive, as well as a lack of screening data from 2016 to the present, which may not reflect the impact of the recent opioid epidemic, the researchers noted. However, the results were strengthened by the large sample size, and the generalizability of the study population.

“Our results regarding prevalence rates and risk factors of HCV antibody among pregnant women in the United States will be valuable to policymakers as they weigh the costs and benefits of universal screening,” Dr. Prasad and associates concluded.

Although universal screening has the potential to be more cost effective, given the small population of pregnant women eligible for treatment and lack of an available treatment, “the rationale is weaker for unique universal HCV screening recommendations for pregnant women,” they said.

By contrast, Sammy Saab, MD, MPH, of the University of California, Los Angeles; Ravina Kullar, PharmD, MPH, of Gilead Sciences, Foster City, Calif.; and Prabhu Gounder, MD, MPH, of the Los Angeles Department of Public Health, wrote an accompanying commentary in favor of universal HCV screening for pregnant women, in part because of the increase in HCV in the younger population overall.

“For many women of reproductive age, pregnancy is one of their few points of contact with their health care provider; therefore, pregnancy could provide a crucial time for targeting this population,” they noted.

Risk-based screening is of limited effectiveness because patients are not identified by way of current screening tools or they decline to reveal risk factors that providers might miss, the editorialists said. Pregnancy has not been shown to affect the accuracy of HCV tests, and identifying infections in mothers allows for screening in children as well.

“The perinatal hepatitis B virus infection program, which has been implemented in several state and local public health departments, could serve as an example for how to conduct surveillance for mothers with HCV infection and to ensure that HCV-exposed children receive appropriate follow-up testing and linkage to care,” the editorialists concluded.

The study was supported in part by multiple grants from the National Institute of Child Health and Human Development. Dr. Prasad disclosed funding from Ohio State University and from Gilead. Coauthors had links with pharmaceutical companies, associations, and organizations – most unrelated to this study. The editorialists had no financial conflicts to disclose.

SOURCES: Prasad M et al. Obstet Gynecol. 2020;135:778-88; Saab S et al. Obstet Gynecol. 2020;135:773-7.

Current risk factors used to screen for hepatitis C should be updated, according to study results of 106,842 pregnant women who underwent screening.

Courtesy NIH

“Because risk-factor screening has obvious limitations, universal screening in pregnancy has been suggested to allow for linkage to postpartum care and identification of children for future testing and treatment,” wrote Mona Prasad, DO, of Ohio State University, Columbus, and colleagues.

In a study published in Obstetrics & Gynecology, the researchers reviewed data from women with singleton pregnancies presenting for prenatal care prior to 23 weeks’ gestation during 2012-2015. Of these, 254 tested positive for the hepatitis C virus (HCV) antibody, for a seroprevalence rate of 2.4 cases per 1,000 women.

The researchers conducted a case-control analysis of 131 women who tested positive and 251 controls to identify HCV infection risk factors based on interviews and chart reviews. They found that risk factors significantly associated with positive HCV antibodies included injection drug use (adjusted odds ratio, 22.9), a history of blood transfusion (aOR, 3.7), having an HCV-infected partner (aOR, 6.3), having had more than three sexual partners (aOR, 5.3), and smoking during pregnancy (aOR, 2.4).

In an unadjusted analysis, the researchers confirmed two of the risk factors currently recommended by the Centers for Disease Control and Prevention for screening for HCV: injection drug use and being born to a mother with HCV infection, but not dialysis, organ transplantation, or HIV infection.

“Our results demonstrate that current risk factors could be contemporized,” Dr. Prasad and colleagues noted. “The currently accepted risk factors such as exposure to clotting factors, dialysis, and organ transplants are unlikely to be found. A thorough assessment of injection drug use history, smoking, transfusions, number of sexual partners, and partners with HCV infection is more sensitive in an obstetric population.”

The study findings were limited by several factors including possible selection bias and inclusion of only 65% of eligible women who were HCV positive, as well as a lack of screening data from 2016 to the present, which may not reflect the impact of the recent opioid epidemic, the researchers noted. However, the results were strengthened by the large sample size, and the generalizability of the study population.

“Our results regarding prevalence rates and risk factors of HCV antibody among pregnant women in the United States will be valuable to policymakers as they weigh the costs and benefits of universal screening,” Dr. Prasad and associates concluded.

Although universal screening has the potential to be more cost effective, given the small population of pregnant women eligible for treatment and lack of an available treatment, “the rationale is weaker for unique universal HCV screening recommendations for pregnant women,” they said.

By contrast, Sammy Saab, MD, MPH, of the University of California, Los Angeles; Ravina Kullar, PharmD, MPH, of Gilead Sciences, Foster City, Calif.; and Prabhu Gounder, MD, MPH, of the Los Angeles Department of Public Health, wrote an accompanying commentary in favor of universal HCV screening for pregnant women, in part because of the increase in HCV in the younger population overall.

“For many women of reproductive age, pregnancy is one of their few points of contact with their health care provider; therefore, pregnancy could provide a crucial time for targeting this population,” they noted.

Risk-based screening is of limited effectiveness because patients are not identified by way of current screening tools or they decline to reveal risk factors that providers might miss, the editorialists said. Pregnancy has not been shown to affect the accuracy of HCV tests, and identifying infections in mothers allows for screening in children as well.

“The perinatal hepatitis B virus infection program, which has been implemented in several state and local public health departments, could serve as an example for how to conduct surveillance for mothers with HCV infection and to ensure that HCV-exposed children receive appropriate follow-up testing and linkage to care,” the editorialists concluded.

The study was supported in part by multiple grants from the National Institute of Child Health and Human Development. Dr. Prasad disclosed funding from Ohio State University and from Gilead. Coauthors had links with pharmaceutical companies, associations, and organizations – most unrelated to this study. The editorialists had no financial conflicts to disclose.

SOURCES: Prasad M et al. Obstet Gynecol. 2020;135:778-88; Saab S et al. Obstet Gynecol. 2020;135:773-7.

The single-tablet antiretroviral regimen of bictegravir, emtricitabine, and tenofovir alafenamide (B/F/TAF) was assessed as being noninferior to two dolutegravir (DTG)-containing regimens among adults aged 50 and over living with HIV, according to a new study.

The study pooled data from two phase 3, randomized, double-blind B/F/TAF studies comparing that regimen with DTG-containing regimens for adults living with HIV who were treatment naive. Anthony Mills, MD, a physician in private practice in West Hollywood, Calif., and his associates reported results at the 144-week mark for the two studies in a poster that was presented as part of the Conference on Retroviruses & Opportunistic Infections, which was presented online this year. CROI organizers chose to hold a virtual meeting because of concerns about the spread of COVID-19.

In the two trials, the B/F/TAF regimen was compared with a DTG and abacavir/lamivudine (DTG + ABC/3TC) regimen, as well as with DTG plus emtricitabine/tenofovir alafenamide (DTG + F/TAF). A total of 629 patients were enrolled in the first study, and 645 in the second. Of these, a total of 196 patients were aged 50 years or older. Across all study arms, most participants (73%-92%) were male, and 20%-37% were black or of African descent. Participants identifying as Hispanic or being of Latino ancestry made up 11%-27% of participants.

About 80%-90% of patients had asymptomatic HIV infection at the time of enrollment, with median CD4 counts ranging from 405-534 cells/mcL across study arms. Patients had a median 4.27-4.53 log (base 10) copies/mL at baseline. In both studies, patients had to have at least 500 HIV-1 RNA copies per mL, and couldn’t have known resistance to any of the study drugs.

At week 144, there were no statistically significant differences in virologic outcomes across study arms in the younger or older age subgroups: 81% of the B/F/TAF patients older than 50 years had fewer than 50 copies/mL of HIV-1 RNA, compared with 83% and 88% of the younger DTG/ABC/3TC and DTG + F/TAF groups meeting this mark, respectively.

Results were similar for the patients aged younger than 50 years, with 82%, 84%, and 83% of the B/F/TAF, DTG/ABC/3TC, and DTG + F/TAF groups having fewer than 50 copies/mL of HIV-1 RNA, respectively.

No patients in either age group showed resistance to any components of the treatment regimens. No treatment-emergent resistance was seen in any study participants, and few adverse events occurred. Those that were seen didn’t occur more frequently in older patients, compared with younger patients, and no patients discontinued their treatment because of renal issues.

Bone mineral density (BMD) was only measured in the study that compared B/F/TAF with DTG/ABC/3TC. Hip BMD decreased slightly in both groups, but the changes were comparable between older and younger participants. For both age groups, differences weren’t significant between the B/F/TAF group and those taking DTG/ABC/3TC. Spine density actually increased slightly in older patients taking B/F/TAF, but the difference between this measure and the slight decrease in older patients taking DTG/ABC/3TC was not significant.

Weight increased over time for all groups, ranging from a gain of 3.4 kg at 144 weeks for older patients taking DTG + F/TAF to 5.3 kg for the same regimen in younger patients, but none of the between-group differences were significant.

All fasting lipids rose for each study arm in both older and younger patients. Some of the between-group differences were statistically significant, but “there were no clinically significant differences in median changes from baseline in fasting lipids” among those aged 50 years or older, noted Dr. Mills and associates.

In terms of safety, no study drug-related discontinuations for renal adverse events occurred in either the B/F/TAF or the DTG + F/TAF groups, and the investigators saw no proximal renal tubulopathy.

The estimated glomerular filtration rate (eGFR) was calculated using the Cockroft-Gault equation. All three antiviral regimens were associated with early drops in eGFR, “consistent with inhibition of tubular creatinine secretion via organic cation transporter 2,” noted Dr. Mills and associates.

Other adverse events were rare in all groups in both older and younger patients, without significant differences between therapies.

The study was supported by Gilead Sciences, which also provided support to Dr. Mills. One coauthor is a Gilead employee.

[email protected]

SOURCE: Mills A et al. CROI 2020, Abstract 2886.

The single-tablet antiretroviral regimen of bictegravir, emtricitabine, and tenofovir alafenamide (B/F/TAF) was assessed as being noninferior to two dolutegravir (DTG)-containing regimens among adults aged 50 and over living with HIV, according to a new study.

The study pooled data from two phase 3, randomized, double-blind B/F/TAF studies comparing that regimen with DTG-containing regimens for adults living with HIV who were treatment naive. Anthony Mills, MD, a physician in private practice in West Hollywood, Calif., and his associates reported results at the 144-week mark for the two studies in a poster that was presented as part of the Conference on Retroviruses & Opportunistic Infections, which was presented online this year. CROI organizers chose to hold a virtual meeting because of concerns about the spread of COVID-19.

In the two trials, the B/F/TAF regimen was compared with a DTG and abacavir/lamivudine (DTG + ABC/3TC) regimen, as well as with DTG plus emtricitabine/tenofovir alafenamide (DTG + F/TAF). A total of 629 patients were enrolled in the first study, and 645 in the second. Of these, a total of 196 patients were aged 50 years or older. Across all study arms, most participants (73%-92%) were male, and 20%-37% were black or of African descent. Participants identifying as Hispanic or being of Latino ancestry made up 11%-27% of participants.

About 80%-90% of patients had asymptomatic HIV infection at the time of enrollment, with median CD4 counts ranging from 405-534 cells/mcL across study arms. Patients had a median 4.27-4.53 log (base 10) copies/mL at baseline. In both studies, patients had to have at least 500 HIV-1 RNA copies per mL, and couldn’t have known resistance to any of the study drugs.

At week 144, there were no statistically significant differences in virologic outcomes across study arms in the younger or older age subgroups: 81% of the B/F/TAF patients older than 50 years had fewer than 50 copies/mL of HIV-1 RNA, compared with 83% and 88% of the younger DTG/ABC/3TC and DTG + F/TAF groups meeting this mark, respectively.

Results were similar for the patients aged younger than 50 years, with 82%, 84%, and 83% of the B/F/TAF, DTG/ABC/3TC, and DTG + F/TAF groups having fewer than 50 copies/mL of HIV-1 RNA, respectively.

No patients in either age group showed resistance to any components of the treatment regimens. No treatment-emergent resistance was seen in any study participants, and few adverse events occurred. Those that were seen didn’t occur more frequently in older patients, compared with younger patients, and no patients discontinued their treatment because of renal issues.

Bone mineral density (BMD) was only measured in the study that compared B/F/TAF with DTG/ABC/3TC. Hip BMD decreased slightly in both groups, but the changes were comparable between older and younger participants. For both age groups, differences weren’t significant between the B/F/TAF group and those taking DTG/ABC/3TC. Spine density actually increased slightly in older patients taking B/F/TAF, but the difference between this measure and the slight decrease in older patients taking DTG/ABC/3TC was not significant.

Weight increased over time for all groups, ranging from a gain of 3.4 kg at 144 weeks for older patients taking DTG + F/TAF to 5.3 kg for the same regimen in younger patients, but none of the between-group differences were significant.

All fasting lipids rose for each study arm in both older and younger patients. Some of the between-group differences were statistically significant, but “there were no clinically significant differences in median changes from baseline in fasting lipids” among those aged 50 years or older, noted Dr. Mills and associates.

In terms of safety, no study drug-related discontinuations for renal adverse events occurred in either the B/F/TAF or the DTG + F/TAF groups, and the investigators saw no proximal renal tubulopathy.

The estimated glomerular filtration rate (eGFR) was calculated using the Cockroft-Gault equation. All three antiviral regimens were associated with early drops in eGFR, “consistent with inhibition of tubular creatinine secretion via organic cation transporter 2,” noted Dr. Mills and associates.

Other adverse events were rare in all groups in both older and younger patients, without significant differences between therapies.

The study was supported by Gilead Sciences, which also provided support to Dr. Mills. One coauthor is a Gilead employee.

[email protected]

SOURCE: Mills A et al. CROI 2020, Abstract 2886.

The single-tablet antiretroviral regimen of bictegravir, emtricitabine, and tenofovir alafenamide (B/F/TAF) was assessed as being noninferior to two dolutegravir (DTG)-containing regimens among adults aged 50 and over living with HIV, according to a new study.

The study pooled data from two phase 3, randomized, double-blind B/F/TAF studies comparing that regimen with DTG-containing regimens for adults living with HIV who were treatment naive. Anthony Mills, MD, a physician in private practice in West Hollywood, Calif., and his associates reported results at the 144-week mark for the two studies in a poster that was presented as part of the Conference on Retroviruses & Opportunistic Infections, which was presented online this year. CROI organizers chose to hold a virtual meeting because of concerns about the spread of COVID-19.

In the two trials, the B/F/TAF regimen was compared with a DTG and abacavir/lamivudine (DTG + ABC/3TC) regimen, as well as with DTG plus emtricitabine/tenofovir alafenamide (DTG + F/TAF). A total of 629 patients were enrolled in the first study, and 645 in the second. Of these, a total of 196 patients were aged 50 years or older. Across all study arms, most participants (73%-92%) were male, and 20%-37% were black or of African descent. Participants identifying as Hispanic or being of Latino ancestry made up 11%-27% of participants.

About 80%-90% of patients had asymptomatic HIV infection at the time of enrollment, with median CD4 counts ranging from 405-534 cells/mcL across study arms. Patients had a median 4.27-4.53 log (base 10) copies/mL at baseline. In both studies, patients had to have at least 500 HIV-1 RNA copies per mL, and couldn’t have known resistance to any of the study drugs.

At week 144, there were no statistically significant differences in virologic outcomes across study arms in the younger or older age subgroups: 81% of the B/F/TAF patients older than 50 years had fewer than 50 copies/mL of HIV-1 RNA, compared with 83% and 88% of the younger DTG/ABC/3TC and DTG + F/TAF groups meeting this mark, respectively.

Results were similar for the patients aged younger than 50 years, with 82%, 84%, and 83% of the B/F/TAF, DTG/ABC/3TC, and DTG + F/TAF groups having fewer than 50 copies/mL of HIV-1 RNA, respectively.

No patients in either age group showed resistance to any components of the treatment regimens. No treatment-emergent resistance was seen in any study participants, and few adverse events occurred. Those that were seen didn’t occur more frequently in older patients, compared with younger patients, and no patients discontinued their treatment because of renal issues.

Bone mineral density (BMD) was only measured in the study that compared B/F/TAF with DTG/ABC/3TC. Hip BMD decreased slightly in both groups, but the changes were comparable between older and younger participants. For both age groups, differences weren’t significant between the B/F/TAF group and those taking DTG/ABC/3TC. Spine density actually increased slightly in older patients taking B/F/TAF, but the difference between this measure and the slight decrease in older patients taking DTG/ABC/3TC was not significant.

Weight increased over time for all groups, ranging from a gain of 3.4 kg at 144 weeks for older patients taking DTG + F/TAF to 5.3 kg for the same regimen in younger patients, but none of the between-group differences were significant.

All fasting lipids rose for each study arm in both older and younger patients. Some of the between-group differences were statistically significant, but “there were no clinically significant differences in median changes from baseline in fasting lipids” among those aged 50 years or older, noted Dr. Mills and associates.

In terms of safety, no study drug-related discontinuations for renal adverse events occurred in either the B/F/TAF or the DTG + F/TAF groups, and the investigators saw no proximal renal tubulopathy.

The estimated glomerular filtration rate (eGFR) was calculated using the Cockroft-Gault equation. All three antiviral regimens were associated with early drops in eGFR, “consistent with inhibition of tubular creatinine secretion via organic cation transporter 2,” noted Dr. Mills and associates.

Other adverse events were rare in all groups in both older and younger patients, without significant differences between therapies.

The study was supported by Gilead Sciences, which also provided support to Dr. Mills. One coauthor is a Gilead employee.

[email protected]

SOURCE: Mills A et al. CROI 2020, Abstract 2886.

Study Overview

Objective. To evaluate the efficacy of cabazitaxel compared to androgen-signaling–targeted inhibitors (ASTIs) in patients with metastatic castration-resistant prostate cancer who have received docetaxel and have progressed within 12 months of treatment with either abiraterone or enzalutamide.

Design. The CARD trial was an international, randomized, open-label phase 3 trial conducted across 13 European countries.

Setting and participants. Eligible patients were 18 years of age or older; had metastatic castration-resistant prostate cancer previously treated with docetaxel; and had disease progression during 12 months of treatment with abiraterone or enzalutamide. All patients had histologically proven prostate cancer, castrate levels of serum testosterone, and disease progression, defined by at least 2 new bone lesions or rising prostate-specific antigen (PSA) level. A total of 255 patients underwent randomization between November 2015 and November 2018, with 129 assigned to receive cabazitaxel and 126 patients assigned to receive an ASTI, 58 of whom received abiraterone and 66 of whom received enzalutamide. Patients who had received an ASTI in the setting of castrate-sensitive metastatic prostate cancer were included.

Intervention. Patients were randomized in a 1:1 fashion to receive either cabazitaxel or abiraterone or enzalutamide. Patients receiving cabazitaxel 25 mg/m² intravenously every 3 weeks also received oral prednisone daily and primary prophylactic granulocyte-colony stimulating factor. Patients assigned to receive an ASTI received abiraterone 1000 mg orally daily with prednisone 5 mg twice daily or enzalutamide 160 mg daily. Patients in the ASTI group who had progressed on abiraterone were assigned to enzalutamide, and alternatively, those on enzalutamide were assigned to abiraterone. Patients were treated until 1 of the following occurred: imaging-based disease progression, unacceptable toxicity, or advancing to an alternative therapy.

Main outcome measures. The primary endpoint was imaging-based progression-free survival, which was defined as the time from randomization until objective tumor progression, progression of bone lesions, or death. The secondary endpoints were overall survival, progression-free survival, PSA response, tumor and pain responses, a new symptomatic skeletal event, and safety.

Results. The median follow-up was 9.2 months. Imaging-based disease progression or death from any cause occurred in 95 (73.6%) participants in the cabazitaxel group, as compared to 101 (80.2%) who were assigned to receive an ASTI. The median imaging-based progression-free survival was 8.0 months in the cabazitaxel group and 3.7 months in the abiraterone/enzalutamide group. The median duration of treatment was longer in those receiving cabazitaxel (22 vs 12.5 weeks). The primary reason for treatment discontinuation was disease progression (in 43.7% of patients receiving cabazitaxel and 71% receiving an ASTI) or an adverse event (19.8% and 8.9%, respectively).

The trial’s secondary endpoints demonstrated improved outcomes in the cabazitaxel group compared to the abiraterone/enzalutamide group. There were 70 deaths (54.2%) in the cabazitaxel group and 83 (65.9%) in the ASTI group. Both the median overall survival (13.6 months in the cabazitaxel group and 11 months in the ASTI group) and the median progression-free survival (4.4 months and 2.7 months, respectively) were improved in those who received cabazitaxel. There was a 50% or greater reduction in the PSA level from baseline in 35.7% of the cabazitaxel group and 13.5% of the ASTI group.

Regarding the safety of the agents, the incidence of adverse events was similar in each group (38.9% in the cabazitaxel group and 38.7% in the ASTI group). Treatment discontinuation occurred more frequently in the cabazitaxel group (19.8%) compared to the ASTI group (8.9%). Adverse events of grade 3 or higher occurred more frequently with cabazitaxel; these were asthenia (4% vs 2.4%), diarrhea (3.2% vs 0), peripheral neuropathy (3.2% vs 0 patients), and febrile neutropenia (3.2% vs 0 patients).

Conclusion. Patients who had disease progression within 12 months on an ASTI and had previously been treated for metastatic castration-resistant prostate cancer with docetaxel had longer imaging-based progression-free survival and overall survival when treated with cabazitaxel compared to those treated with an alternative ASTI. Other clinical outcomes, including overall survival and progression-free survival, were also improved in the cabazitaxel group.

Commentary

Four ASTIs are approved for therapy in men with advanced prostate cancer. The next line of therapy following progression on an ASTI, whether to consider second-line androgen targeted inhibitors or proceed to taxane-based chemotherapy, has been unclear. The current CARD trial sought to answer this question and provides evidence that cabazitaxel is the next line of therapy for these patients. The trial’s primary endpoint, imaging-based disease progression, was reported in 73.6% of those who received cabazitaxel and in 80.2% of those who received abiraterone or enzalutamide. Patients treated with cabazitaxel had a longer imaging-based progression-free survival (8.0 months vs 3.7 months) and a longer duration of treatment (22 vs 12.5 weeks).

Because there is clinical evidence of cross-resistance between different ASTIs, the value of sequential therapy has been unclear. Emergence of androgen-receptor splice variant 7 (AR-V7) mutational status in circulating tumor cells is associated with poor outcomes with secondary androgen-signaling inhibitor therapy, and may be an indicator of resistance to subsequent androgen-signaling inhibitors.^1,2 In the PROPHECY trial, the response rates to subsequent androgen targeted therapy in patients with AR-V7 mutations ranged from 30% to 40%.³ Understanding how AR-V7 mutational status may impact such outcomes will certainly help define whether a subgroup exists in whom use of second-line androgen signaling inhibitors may be considered.

The patients enrolled in the current study appear to represent a subgroup of patients with biologically aggressive disease or with inherent resistance to ASTIs. The patients included in this study progressed within 1 year of androgen targeted therapy, which is representative of a more aggressive population of patients who may be hormone insensitive and derive more benefit from chemotherapy. Initial androgen deprivation therapy was given for 13.7 and 12.6 months to the cabazitaxel and enzalutamide/abiraterone arms, respectively, prior to developing castrate-resistant prostate cancer. Patients enrolled in this study also previously received docetaxel, deselecting those who are taxane-resistant and therefore may be less likely to respond to additional taxane-based therapy. Detection of AR-V7 splice variant expression in circulating tumor cells, consideration of biomarker data, and sensitivity to taxanes may help guide decisions regarding the use of sequential androgen-targeted agents; however, there has been no clear data to guide such an approach. It is also important to consider that, because this is a European study, the approved dose given in this trial was 25 mg/m². The PROSELICA trial previously demonstrated noninferiority of 20 mg/m² compared with 25 mg/m², with fewer adverse events, which is the dose now utilized in the United States.⁴

The adverse events of grade 3 or greater occurring in the cabazitaxel group should be discussed with patients, including fatigue, diarrhea, peripheral neuropathy, and febrile neutropenia.

The data from the CARD trial provide guidance regarding therapy sequencing in those with advanced prostate cancer after progression on first-line androgen targeted inhibitors and docetaxel; however, further work is needed to understand the universal application of this data in this cohort.

Applications in Clinical Practice

Patients with metastatic castration-resistant prostate cancer who have received docetaxel and progressed on an androgen-signaling inhibitor within 12 months should be considered for cabazitaxel over an alternative androgen-signaling inhibitor. This decision should be based on several factors, including AR-V7 mutational status, duration of androgen deprivation therapy, and hormone and taxane sensitivity in the past. Future studies are likely to incorporate genomic biomarkers rather than clinical criteria alone to make treatment decisions.

–Britni Souther, DO, and Daniel Isaac, DO, MS, Michigan State University, East Lansing, MI

Study Overview

Objective. To evaluate the efficacy of cabazitaxel compared to androgen-signaling–targeted inhibitors (ASTIs) in patients with metastatic castration-resistant prostate cancer who have received docetaxel and have progressed within 12 months of treatment with either abiraterone or enzalutamide.

Design. The CARD trial was an international, randomized, open-label phase 3 trial conducted across 13 European countries.

Setting and participants. Eligible patients were 18 years of age or older; had metastatic castration-resistant prostate cancer previously treated with docetaxel; and had disease progression during 12 months of treatment with abiraterone or enzalutamide. All patients had histologically proven prostate cancer, castrate levels of serum testosterone, and disease progression, defined by at least 2 new bone lesions or rising prostate-specific antigen (PSA) level. A total of 255 patients underwent randomization between November 2015 and November 2018, with 129 assigned to receive cabazitaxel and 126 patients assigned to receive an ASTI, 58 of whom received abiraterone and 66 of whom received enzalutamide. Patients who had received an ASTI in the setting of castrate-sensitive metastatic prostate cancer were included.

Intervention. Patients were randomized in a 1:1 fashion to receive either cabazitaxel or abiraterone or enzalutamide. Patients receiving cabazitaxel 25 mg/m² intravenously every 3 weeks also received oral prednisone daily and primary prophylactic granulocyte-colony stimulating factor. Patients assigned to receive an ASTI received abiraterone 1000 mg orally daily with prednisone 5 mg twice daily or enzalutamide 160 mg daily. Patients in the ASTI group who had progressed on abiraterone were assigned to enzalutamide, and alternatively, those on enzalutamide were assigned to abiraterone. Patients were treated until 1 of the following occurred: imaging-based disease progression, unacceptable toxicity, or advancing to an alternative therapy.

Main outcome measures. The primary endpoint was imaging-based progression-free survival, which was defined as the time from randomization until objective tumor progression, progression of bone lesions, or death. The secondary endpoints were overall survival, progression-free survival, PSA response, tumor and pain responses, a new symptomatic skeletal event, and safety.

Results. The median follow-up was 9.2 months. Imaging-based disease progression or death from any cause occurred in 95 (73.6%) participants in the cabazitaxel group, as compared to 101 (80.2%) who were assigned to receive an ASTI. The median imaging-based progression-free survival was 8.0 months in the cabazitaxel group and 3.7 months in the abiraterone/enzalutamide group. The median duration of treatment was longer in those receiving cabazitaxel (22 vs 12.5 weeks). The primary reason for treatment discontinuation was disease progression (in 43.7% of patients receiving cabazitaxel and 71% receiving an ASTI) or an adverse event (19.8% and 8.9%, respectively).

The trial’s secondary endpoints demonstrated improved outcomes in the cabazitaxel group compared to the abiraterone/enzalutamide group. There were 70 deaths (54.2%) in the cabazitaxel group and 83 (65.9%) in the ASTI group. Both the median overall survival (13.6 months in the cabazitaxel group and 11 months in the ASTI group) and the median progression-free survival (4.4 months and 2.7 months, respectively) were improved in those who received cabazitaxel. There was a 50% or greater reduction in the PSA level from baseline in 35.7% of the cabazitaxel group and 13.5% of the ASTI group.

Regarding the safety of the agents, the incidence of adverse events was similar in each group (38.9% in the cabazitaxel group and 38.7% in the ASTI group). Treatment discontinuation occurred more frequently in the cabazitaxel group (19.8%) compared to the ASTI group (8.9%). Adverse events of grade 3 or higher occurred more frequently with cabazitaxel; these were asthenia (4% vs 2.4%), diarrhea (3.2% vs 0), peripheral neuropathy (3.2% vs 0 patients), and febrile neutropenia (3.2% vs 0 patients).

Conclusion. Patients who had disease progression within 12 months on an ASTI and had previously been treated for metastatic castration-resistant prostate cancer with docetaxel had longer imaging-based progression-free survival and overall survival when treated with cabazitaxel compared to those treated with an alternative ASTI. Other clinical outcomes, including overall survival and progression-free survival, were also improved in the cabazitaxel group.

Commentary

Four ASTIs are approved for therapy in men with advanced prostate cancer. The next line of therapy following progression on an ASTI, whether to consider second-line androgen targeted inhibitors or proceed to taxane-based chemotherapy, has been unclear. The current CARD trial sought to answer this question and provides evidence that cabazitaxel is the next line of therapy for these patients. The trial’s primary endpoint, imaging-based disease progression, was reported in 73.6% of those who received cabazitaxel and in 80.2% of those who received abiraterone or enzalutamide. Patients treated with cabazitaxel had a longer imaging-based progression-free survival (8.0 months vs 3.7 months) and a longer duration of treatment (22 vs 12.5 weeks).

Because there is clinical evidence of cross-resistance between different ASTIs, the value of sequential therapy has been unclear. Emergence of androgen-receptor splice variant 7 (AR-V7) mutational status in circulating tumor cells is associated with poor outcomes with secondary androgen-signaling inhibitor therapy, and may be an indicator of resistance to subsequent androgen-signaling inhibitors.^1,2 In the PROPHECY trial, the response rates to subsequent androgen targeted therapy in patients with AR-V7 mutations ranged from 30% to 40%.³ Understanding how AR-V7 mutational status may impact such outcomes will certainly help define whether a subgroup exists in whom use of second-line androgen signaling inhibitors may be considered.

The patients enrolled in the current study appear to represent a subgroup of patients with biologically aggressive disease or with inherent resistance to ASTIs. The patients included in this study progressed within 1 year of androgen targeted therapy, which is representative of a more aggressive population of patients who may be hormone insensitive and derive more benefit from chemotherapy. Initial androgen deprivation therapy was given for 13.7 and 12.6 months to the cabazitaxel and enzalutamide/abiraterone arms, respectively, prior to developing castrate-resistant prostate cancer. Patients enrolled in this study also previously received docetaxel, deselecting those who are taxane-resistant and therefore may be less likely to respond to additional taxane-based therapy. Detection of AR-V7 splice variant expression in circulating tumor cells, consideration of biomarker data, and sensitivity to taxanes may help guide decisions regarding the use of sequential androgen-targeted agents; however, there has been no clear data to guide such an approach. It is also important to consider that, because this is a European study, the approved dose given in this trial was 25 mg/m². The PROSELICA trial previously demonstrated noninferiority of 20 mg/m² compared with 25 mg/m², with fewer adverse events, which is the dose now utilized in the United States.⁴

The adverse events of grade 3 or greater occurring in the cabazitaxel group should be discussed with patients, including fatigue, diarrhea, peripheral neuropathy, and febrile neutropenia.

The data from the CARD trial provide guidance regarding therapy sequencing in those with advanced prostate cancer after progression on first-line androgen targeted inhibitors and docetaxel; however, further work is needed to understand the universal application of this data in this cohort.

Applications in Clinical Practice

Patients with metastatic castration-resistant prostate cancer who have received docetaxel and progressed on an androgen-signaling inhibitor within 12 months should be considered for cabazitaxel over an alternative androgen-signaling inhibitor. This decision should be based on several factors, including AR-V7 mutational status, duration of androgen deprivation therapy, and hormone and taxane sensitivity in the past. Future studies are likely to incorporate genomic biomarkers rather than clinical criteria alone to make treatment decisions.

–Britni Souther, DO, and Daniel Isaac, DO, MS, Michigan State University, East Lansing, MI

Study Overview

Objective. To evaluate the efficacy of cabazitaxel compared to androgen-signaling–targeted inhibitors (ASTIs) in patients with metastatic castration-resistant prostate cancer who have received docetaxel and have progressed within 12 months of treatment with either abiraterone or enzalutamide.

Design. The CARD trial was an international, randomized, open-label phase 3 trial conducted across 13 European countries.

Setting and participants. Eligible patients were 18 years of age or older; had metastatic castration-resistant prostate cancer previously treated with docetaxel; and had disease progression during 12 months of treatment with abiraterone or enzalutamide. All patients had histologically proven prostate cancer, castrate levels of serum testosterone, and disease progression, defined by at least 2 new bone lesions or rising prostate-specific antigen (PSA) level. A total of 255 patients underwent randomization between November 2015 and November 2018, with 129 assigned to receive cabazitaxel and 126 patients assigned to receive an ASTI, 58 of whom received abiraterone and 66 of whom received enzalutamide. Patients who had received an ASTI in the setting of castrate-sensitive metastatic prostate cancer were included.

Intervention. Patients were randomized in a 1:1 fashion to receive either cabazitaxel or abiraterone or enzalutamide. Patients receiving cabazitaxel 25 mg/m² intravenously every 3 weeks also received oral prednisone daily and primary prophylactic granulocyte-colony stimulating factor. Patients assigned to receive an ASTI received abiraterone 1000 mg orally daily with prednisone 5 mg twice daily or enzalutamide 160 mg daily. Patients in the ASTI group who had progressed on abiraterone were assigned to enzalutamide, and alternatively, those on enzalutamide were assigned to abiraterone. Patients were treated until 1 of the following occurred: imaging-based disease progression, unacceptable toxicity, or advancing to an alternative therapy.

Main outcome measures. The primary endpoint was imaging-based progression-free survival, which was defined as the time from randomization until objective tumor progression, progression of bone lesions, or death. The secondary endpoints were overall survival, progression-free survival, PSA response, tumor and pain responses, a new symptomatic skeletal event, and safety.

Results. The median follow-up was 9.2 months. Imaging-based disease progression or death from any cause occurred in 95 (73.6%) participants in the cabazitaxel group, as compared to 101 (80.2%) who were assigned to receive an ASTI. The median imaging-based progression-free survival was 8.0 months in the cabazitaxel group and 3.7 months in the abiraterone/enzalutamide group. The median duration of treatment was longer in those receiving cabazitaxel (22 vs 12.5 weeks). The primary reason for treatment discontinuation was disease progression (in 43.7% of patients receiving cabazitaxel and 71% receiving an ASTI) or an adverse event (19.8% and 8.9%, respectively).

The trial’s secondary endpoints demonstrated improved outcomes in the cabazitaxel group compared to the abiraterone/enzalutamide group. There were 70 deaths (54.2%) in the cabazitaxel group and 83 (65.9%) in the ASTI group. Both the median overall survival (13.6 months in the cabazitaxel group and 11 months in the ASTI group) and the median progression-free survival (4.4 months and 2.7 months, respectively) were improved in those who received cabazitaxel. There was a 50% or greater reduction in the PSA level from baseline in 35.7% of the cabazitaxel group and 13.5% of the ASTI group.

Regarding the safety of the agents, the incidence of adverse events was similar in each group (38.9% in the cabazitaxel group and 38.7% in the ASTI group). Treatment discontinuation occurred more frequently in the cabazitaxel group (19.8%) compared to the ASTI group (8.9%). Adverse events of grade 3 or higher occurred more frequently with cabazitaxel; these were asthenia (4% vs 2.4%), diarrhea (3.2% vs 0), peripheral neuropathy (3.2% vs 0 patients), and febrile neutropenia (3.2% vs 0 patients).

Conclusion. Patients who had disease progression within 12 months on an ASTI and had previously been treated for metastatic castration-resistant prostate cancer with docetaxel had longer imaging-based progression-free survival and overall survival when treated with cabazitaxel compared to those treated with an alternative ASTI. Other clinical outcomes, including overall survival and progression-free survival, were also improved in the cabazitaxel group.

Commentary

Four ASTIs are approved for therapy in men with advanced prostate cancer. The next line of therapy following progression on an ASTI, whether to consider second-line androgen targeted inhibitors or proceed to taxane-based chemotherapy, has been unclear. The current CARD trial sought to answer this question and provides evidence that cabazitaxel is the next line of therapy for these patients. The trial’s primary endpoint, imaging-based disease progression, was reported in 73.6% of those who received cabazitaxel and in 80.2% of those who received abiraterone or enzalutamide. Patients treated with cabazitaxel had a longer imaging-based progression-free survival (8.0 months vs 3.7 months) and a longer duration of treatment (22 vs 12.5 weeks).

Because there is clinical evidence of cross-resistance between different ASTIs, the value of sequential therapy has been unclear. Emergence of androgen-receptor splice variant 7 (AR-V7) mutational status in circulating tumor cells is associated with poor outcomes with secondary androgen-signaling inhibitor therapy, and may be an indicator of resistance to subsequent androgen-signaling inhibitors.^1,2 In the PROPHECY trial, the response rates to subsequent androgen targeted therapy in patients with AR-V7 mutations ranged from 30% to 40%.³ Understanding how AR-V7 mutational status may impact such outcomes will certainly help define whether a subgroup exists in whom use of second-line androgen signaling inhibitors may be considered.

The patients enrolled in the current study appear to represent a subgroup of patients with biologically aggressive disease or with inherent resistance to ASTIs. The patients included in this study progressed within 1 year of androgen targeted therapy, which is representative of a more aggressive population of patients who may be hormone insensitive and derive more benefit from chemotherapy. Initial androgen deprivation therapy was given for 13.7 and 12.6 months to the cabazitaxel and enzalutamide/abiraterone arms, respectively, prior to developing castrate-resistant prostate cancer. Patients enrolled in this study also previously received docetaxel, deselecting those who are taxane-resistant and therefore may be less likely to respond to additional taxane-based therapy. Detection of AR-V7 splice variant expression in circulating tumor cells, consideration of biomarker data, and sensitivity to taxanes may help guide decisions regarding the use of sequential androgen-targeted agents; however, there has been no clear data to guide such an approach. It is also important to consider that, because this is a European study, the approved dose given in this trial was 25 mg/m². The PROSELICA trial previously demonstrated noninferiority of 20 mg/m² compared with 25 mg/m², with fewer adverse events, which is the dose now utilized in the United States.⁴

The adverse events of grade 3 or greater occurring in the cabazitaxel group should be discussed with patients, including fatigue, diarrhea, peripheral neuropathy, and febrile neutropenia.

The data from the CARD trial provide guidance regarding therapy sequencing in those with advanced prostate cancer after progression on first-line androgen targeted inhibitors and docetaxel; however, further work is needed to understand the universal application of this data in this cohort.

Applications in Clinical Practice

Patients with metastatic castration-resistant prostate cancer who have received docetaxel and progressed on an androgen-signaling inhibitor within 12 months should be considered for cabazitaxel over an alternative androgen-signaling inhibitor. This decision should be based on several factors, including AR-V7 mutational status, duration of androgen deprivation therapy, and hormone and taxane sensitivity in the past. Future studies are likely to incorporate genomic biomarkers rather than clinical criteria alone to make treatment decisions.

–Britni Souther, DO, and Daniel Isaac, DO, MS, Michigan State University, East Lansing, MI

Physicians and pharmacists are reporting shortages of hydroxychloroquine and chloroquine following President Trump’s promotion of the medications as potential COVID-19 treatments, leaving patients with rheumatic diseases wondering how it will impact their access.

The American Medical Association, the American Pharmacists Association, and the American Society of Health-System Pharmacists, issued a joint statement that strongly opposed prophylactic prescribing of these medications for COVID-19 or stockpiling them in anticipation of use for COVID-19. The concerns over shortages have also prompted the American College of Rheumatology, American Academy of Dermatology, Arthritis Foundation, and Lupus Foundation of America to send a joint statement to the Trump administration and the nation’s governors highlighting critical hydroxychloroquine access issues and asking policymakers to work together with health care providers and patient communities to ensure continued availability of these drugs.

Now rheumatologists are trying to reassure patients with lupus or other rheumatic diseases who take the antimalarials that they will be available and are relatively easy for manufacturers to produce.

In a Q and A interview, NYU Langone Health rheumatology division director and Lupus Center director Jill P. Buyon, MD, and associate professor of rheumatology, Peter M. Izmirly, MD, noted that, while shortages have been reported across the United States because of large increases in off-label prescribing, many of the drugs’ manufacturers have committed to donating millions of doses and/or stepping up production to meet demand.

Later in this article, Michael H. Pillinger, MD, a rheumatologist and professor of medicine, biochemistry, and molecular pharmacology at NYU Langone Health, New York, answered questions about a new multicenter study called COLCORONA getting underway to test the anti-inflammatory drug colchicine. The answers in this Q&A have been edited for length and clarity. 
 

Questions about hydroxychloroquine shortage

Q: What is the current situation with hydroxychloroquine in your practice?

A: We have been getting calls from our patients asking about getting refills for hydroxychloroquine. Our group has been calling local pharmacies asking about the availability of hydroxychloroquine, and we are compiling a list of pharmacies in New York with current availabilities to share with patients. We are somewhat limited by our electronic health record system, Epic, which can only send a prescription to one pharmacy, so that has placed some limitations on knowing where it is available. Some pharmacies have not had hydroxychloroquine available, while others have. We have also been encouraging patients to check online and look for mail-order possibilities for 90-day supplies.

Nearly all prescriptions are for generic hydroxychloroquine. Branded hydroxychloroquine (Plaquenil) is much more expensive, and we can run into obstacles with getting it approved by insurers, too.
 

Q: What are you telling patients who seek to refill their prescription or call with concerns? Is it feasible for patients to stop hydroxychloroquine or cut their dosage if necessary?

A: If someone’s been on hydroxychloroquine and has benefited from its use there’s no reason to come off it at this time, and given the possibility that it may have an effect on COVID-19, that is all the better. But we want to reassure patients that they can get the drug and that it is not difficult to manufacture.

Given the significantly higher risk of disease flare that was first described in lupus patients who discontinued hydroxychloroquine in the Canadian Hydroxychloroquine Study Group’s 1991 randomized, controlled trial, it is not advisable for patients to stop the drug.

Some patients do split their dosage day-to-day if they are taking less than 400 mg daily, such that someone taking 300 mg daily may take two 200-mg tablets one day and just one 200-mg tablet the next day, and so on. To avoid eye toxicity that can occur after years of taking the drug, hydroxychloroquine is generally prescribed based on weight at 5 mg/kg.

The drug also stays in the body for quite a while [often up to 3 months and even longer], so that is helpful for patients to know.

Given the current situation and the possibility of its effectiveness against COVID-19, it is ironic that we are actually trying to recruit older lupus patients who have had long-term stable disease while on hydroxychloroquine to a trial of stopping the drug to reduce the risk of developing the side effect of retinopathy. We want to see if patients can safely withdraw hydroxychloroquine without flaring, so we hope to not run into enrollment difficulties based on the current situation with COVID-19.
 

Q: How do you view the balance between having enough hydroxychloroquine for patients with lupus or other rheumatic diseases and its use in COVID-19 patients?

A: We want to reassure patients that hydroxychloroquine will be available, and there is no reason to hoard the drug or to worry excessively about being unable to obtain it. Efforts to increase production by Mylan, Teva, Sanofi, Novartis, and other manufacturers of hydroxychloroquine should really help out.

Q: Are there pharmacy restrictions on prescription amounts?

A: This is not universal at this time, but some institutions are cutting back and offering only 1-month supplies.
 

Colchicine COVID-19 trial underway

Dr. Pillinger, of NYU Langone Health, explored the COLCORONA study of colchicine as a treatment for people infected with COVID-19 and the worry that shortage concerns may arise for it, too. 

Q: What is the general availability of colchicine and its susceptibility to shortage?

A: There are two major manufacturers of colchicine in the United States, Takeda and Hikma, who together manufacture the majority of the drug.

The greatest use of colchicine in the United States is for gout, which affects approximately 4 million Americans, but the drug is not used chronically, so a much smaller number of patients are using colchicine at any one time. Colchicine is also used for other inflammatory conditions, primarily calcium pyrophosphate crystal disease and familial Mediterranean fever (FMF is rare in the United States). Cardiologists also regularly prescribe colchicine in pericarditis for short-term use. Physicians may use it off label for other purposes, too.

Overall, the number of patients using colchicine is much larger than that for the use of hydroxychloroquine, for example, suggesting that the immediate risk of shortage could be lower. However, if individuals started using it off label, or prescribing inappropriately for the COVID-19 indication, the supply would rapidly run short.
 

Q: What other points are there to consider regarding the use of colchicine to treat COVID-19?

A: There is no evidence – zero – that colchicine has any benefit for COVID-19, not even case reports. There is some rationale that it might be beneficial, but that is exactly why the COLCORONA trial would be logical to try.

The COLCORONA trial is exactly the kind of trial that would be needed for assessing colchicine, and it is big enough and happening quickly enough to get an answer. But if people start to use colchicine off label, we may never know the truth.

While colchicine can be used safely in most people, it can be very problematic and requires an experienced doctor’s supervision. Overdoses can be fatal, and colchicine interacts with many drugs, all of which require dose adjustment and some of which must be stopped in order to use colchicine – it isn’t candy. Some of the other drugs being looked at for COVID-19 in fact may interact with colchicine.

Colchicine must also be dose adjusted for kidney disease, and, in some of the COVID-19 patients, kidney function changes rapidly. So again, its use would require expert supervision even if there were evidence for its utility.

The side effects of colchicine, if mis-dosed, can be very unpleasant, including nausea, vomiting, and diarrhea. Even at the apparent right dose, some people will get these side effects, so colchicine has to be something that works to make the risk/benefit ratio worth it.

Some preparations of colchicine are made combined with probenecid, a gout drug. This is even more problematic because probenecid can raise the level of drugs excreted by the kidney and could affect other treatments.

So in sum, what may be a good idea in theory can turn out to be a disastrous idea in practice, and here we have nothing but theory. This is not an agent to use randomly; the studies will be rushed out quickly and hopefully will give us the knowledge to know what to do.

Dr. Izmirly and Dr. Buyon said they have research grants with the National Institutes of Health to study hydroxychloroquine in patients with lupus and in anti–SSA/Ro-positive pregnant women with a previous child with congenital heart block. Dr. Pillinger reports that he has an investigator-initiated grant from Hikma to study colchicine in osteoarthritis.

[email protected]

This article was reformatted on 3/30/2020 for clarity. 

Physicians and pharmacists are reporting shortages of hydroxychloroquine and chloroquine following President Trump’s promotion of the medications as potential COVID-19 treatments, leaving patients with rheumatic diseases wondering how it will impact their access.

The American Medical Association, the American Pharmacists Association, and the American Society of Health-System Pharmacists, issued a joint statement that strongly opposed prophylactic prescribing of these medications for COVID-19 or stockpiling them in anticipation of use for COVID-19. The concerns over shortages have also prompted the American College of Rheumatology, American Academy of Dermatology, Arthritis Foundation, and Lupus Foundation of America to send a joint statement to the Trump administration and the nation’s governors highlighting critical hydroxychloroquine access issues and asking policymakers to work together with health care providers and patient communities to ensure continued availability of these drugs.

Now rheumatologists are trying to reassure patients with lupus or other rheumatic diseases who take the antimalarials that they will be available and are relatively easy for manufacturers to produce.

In a Q and A interview, NYU Langone Health rheumatology division director and Lupus Center director Jill P. Buyon, MD, and associate professor of rheumatology, Peter M. Izmirly, MD, noted that, while shortages have been reported across the United States because of large increases in off-label prescribing, many of the drugs’ manufacturers have committed to donating millions of doses and/or stepping up production to meet demand.

Later in this article, Michael H. Pillinger, MD, a rheumatologist and professor of medicine, biochemistry, and molecular pharmacology at NYU Langone Health, New York, answered questions about a new multicenter study called COLCORONA getting underway to test the anti-inflammatory drug colchicine. The answers in this Q&A have been edited for length and clarity. 
 

Questions about hydroxychloroquine shortage

Q: What is the current situation with hydroxychloroquine in your practice?

A: We have been getting calls from our patients asking about getting refills for hydroxychloroquine. Our group has been calling local pharmacies asking about the availability of hydroxychloroquine, and we are compiling a list of pharmacies in New York with current availabilities to share with patients. We are somewhat limited by our electronic health record system, Epic, which can only send a prescription to one pharmacy, so that has placed some limitations on knowing where it is available. Some pharmacies have not had hydroxychloroquine available, while others have. We have also been encouraging patients to check online and look for mail-order possibilities for 90-day supplies.

Nearly all prescriptions are for generic hydroxychloroquine. Branded hydroxychloroquine (Plaquenil) is much more expensive, and we can run into obstacles with getting it approved by insurers, too.
 

Q: What are you telling patients who seek to refill their prescription or call with concerns? Is it feasible for patients to stop hydroxychloroquine or cut their dosage if necessary?

A: If someone’s been on hydroxychloroquine and has benefited from its use there’s no reason to come off it at this time, and given the possibility that it may have an effect on COVID-19, that is all the better. But we want to reassure patients that they can get the drug and that it is not difficult to manufacture.

Given the significantly higher risk of disease flare that was first described in lupus patients who discontinued hydroxychloroquine in the Canadian Hydroxychloroquine Study Group’s 1991 randomized, controlled trial, it is not advisable for patients to stop the drug.

Some patients do split their dosage day-to-day if they are taking less than 400 mg daily, such that someone taking 300 mg daily may take two 200-mg tablets one day and just one 200-mg tablet the next day, and so on. To avoid eye toxicity that can occur after years of taking the drug, hydroxychloroquine is generally prescribed based on weight at 5 mg/kg.

The drug also stays in the body for quite a while [often up to 3 months and even longer], so that is helpful for patients to know.

Given the current situation and the possibility of its effectiveness against COVID-19, it is ironic that we are actually trying to recruit older lupus patients who have had long-term stable disease while on hydroxychloroquine to a trial of stopping the drug to reduce the risk of developing the side effect of retinopathy. We want to see if patients can safely withdraw hydroxychloroquine without flaring, so we hope to not run into enrollment difficulties based on the current situation with COVID-19.
 

Q: How do you view the balance between having enough hydroxychloroquine for patients with lupus or other rheumatic diseases and its use in COVID-19 patients?

A: We want to reassure patients that hydroxychloroquine will be available, and there is no reason to hoard the drug or to worry excessively about being unable to obtain it. Efforts to increase production by Mylan, Teva, Sanofi, Novartis, and other manufacturers of hydroxychloroquine should really help out.

Q: Are there pharmacy restrictions on prescription amounts?

A: This is not universal at this time, but some institutions are cutting back and offering only 1-month supplies.
 

Colchicine COVID-19 trial underway

Dr. Pillinger, of NYU Langone Health, explored the COLCORONA study of colchicine as a treatment for people infected with COVID-19 and the worry that shortage concerns may arise for it, too. 

Q: What is the general availability of colchicine and its susceptibility to shortage?

A: There are two major manufacturers of colchicine in the United States, Takeda and Hikma, who together manufacture the majority of the drug.

The greatest use of colchicine in the United States is for gout, which affects approximately 4 million Americans, but the drug is not used chronically, so a much smaller number of patients are using colchicine at any one time. Colchicine is also used for other inflammatory conditions, primarily calcium pyrophosphate crystal disease and familial Mediterranean fever (FMF is rare in the United States). Cardiologists also regularly prescribe colchicine in pericarditis for short-term use. Physicians may use it off label for other purposes, too.

Overall, the number of patients using colchicine is much larger than that for the use of hydroxychloroquine, for example, suggesting that the immediate risk of shortage could be lower. However, if individuals started using it off label, or prescribing inappropriately for the COVID-19 indication, the supply would rapidly run short.
 

Q: What other points are there to consider regarding the use of colchicine to treat COVID-19?

A: There is no evidence – zero – that colchicine has any benefit for COVID-19, not even case reports. There is some rationale that it might be beneficial, but that is exactly why the COLCORONA trial would be logical to try.

The COLCORONA trial is exactly the kind of trial that would be needed for assessing colchicine, and it is big enough and happening quickly enough to get an answer. But if people start to use colchicine off label, we may never know the truth.

While colchicine can be used safely in most people, it can be very problematic and requires an experienced doctor’s supervision. Overdoses can be fatal, and colchicine interacts with many drugs, all of which require dose adjustment and some of which must be stopped in order to use colchicine – it isn’t candy. Some of the other drugs being looked at for COVID-19 in fact may interact with colchicine.

Colchicine must also be dose adjusted for kidney disease, and, in some of the COVID-19 patients, kidney function changes rapidly. So again, its use would require expert supervision even if there were evidence for its utility.

The side effects of colchicine, if mis-dosed, can be very unpleasant, including nausea, vomiting, and diarrhea. Even at the apparent right dose, some people will get these side effects, so colchicine has to be something that works to make the risk/benefit ratio worth it.

Some preparations of colchicine are made combined with probenecid, a gout drug. This is even more problematic because probenecid can raise the level of drugs excreted by the kidney and could affect other treatments.

So in sum, what may be a good idea in theory can turn out to be a disastrous idea in practice, and here we have nothing but theory. This is not an agent to use randomly; the studies will be rushed out quickly and hopefully will give us the knowledge to know what to do.

Dr. Izmirly and Dr. Buyon said they have research grants with the National Institutes of Health to study hydroxychloroquine in patients with lupus and in anti–SSA/Ro-positive pregnant women with a previous child with congenital heart block. Dr. Pillinger reports that he has an investigator-initiated grant from Hikma to study colchicine in osteoarthritis.

[email protected]

This article was reformatted on 3/30/2020 for clarity. 

Physicians and pharmacists are reporting shortages of hydroxychloroquine and chloroquine following President Trump’s promotion of the medications as potential COVID-19 treatments, leaving patients with rheumatic diseases wondering how it will impact their access.

The American Medical Association, the American Pharmacists Association, and the American Society of Health-System Pharmacists, issued a joint statement that strongly opposed prophylactic prescribing of these medications for COVID-19 or stockpiling them in anticipation of use for COVID-19. The concerns over shortages have also prompted the American College of Rheumatology, American Academy of Dermatology, Arthritis Foundation, and Lupus Foundation of America to send a joint statement to the Trump administration and the nation’s governors highlighting critical hydroxychloroquine access issues and asking policymakers to work together with health care providers and patient communities to ensure continued availability of these drugs.

Now rheumatologists are trying to reassure patients with lupus or other rheumatic diseases who take the antimalarials that they will be available and are relatively easy for manufacturers to produce.

In a Q and A interview, NYU Langone Health rheumatology division director and Lupus Center director Jill P. Buyon, MD, and associate professor of rheumatology, Peter M. Izmirly, MD, noted that, while shortages have been reported across the United States because of large increases in off-label prescribing, many of the drugs’ manufacturers have committed to donating millions of doses and/or stepping up production to meet demand.

Later in this article, Michael H. Pillinger, MD, a rheumatologist and professor of medicine, biochemistry, and molecular pharmacology at NYU Langone Health, New York, answered questions about a new multicenter study called COLCORONA getting underway to test the anti-inflammatory drug colchicine. The answers in this Q&A have been edited for length and clarity. 
 

Questions about hydroxychloroquine shortage

Q: What is the current situation with hydroxychloroquine in your practice?

A: We have been getting calls from our patients asking about getting refills for hydroxychloroquine. Our group has been calling local pharmacies asking about the availability of hydroxychloroquine, and we are compiling a list of pharmacies in New York with current availabilities to share with patients. We are somewhat limited by our electronic health record system, Epic, which can only send a prescription to one pharmacy, so that has placed some limitations on knowing where it is available. Some pharmacies have not had hydroxychloroquine available, while others have. We have also been encouraging patients to check online and look for mail-order possibilities for 90-day supplies.

Nearly all prescriptions are for generic hydroxychloroquine. Branded hydroxychloroquine (Plaquenil) is much more expensive, and we can run into obstacles with getting it approved by insurers, too.
 

Q: What are you telling patients who seek to refill their prescription or call with concerns? Is it feasible for patients to stop hydroxychloroquine or cut their dosage if necessary?

A: If someone’s been on hydroxychloroquine and has benefited from its use there’s no reason to come off it at this time, and given the possibility that it may have an effect on COVID-19, that is all the better. But we want to reassure patients that they can get the drug and that it is not difficult to manufacture.

Given the significantly higher risk of disease flare that was first described in lupus patients who discontinued hydroxychloroquine in the Canadian Hydroxychloroquine Study Group’s 1991 randomized, controlled trial, it is not advisable for patients to stop the drug.

Some patients do split their dosage day-to-day if they are taking less than 400 mg daily, such that someone taking 300 mg daily may take two 200-mg tablets one day and just one 200-mg tablet the next day, and so on. To avoid eye toxicity that can occur after years of taking the drug, hydroxychloroquine is generally prescribed based on weight at 5 mg/kg.

The drug also stays in the body for quite a while [often up to 3 months and even longer], so that is helpful for patients to know.

Given the current situation and the possibility of its effectiveness against COVID-19, it is ironic that we are actually trying to recruit older lupus patients who have had long-term stable disease while on hydroxychloroquine to a trial of stopping the drug to reduce the risk of developing the side effect of retinopathy. We want to see if patients can safely withdraw hydroxychloroquine without flaring, so we hope to not run into enrollment difficulties based on the current situation with COVID-19.
 

Q: How do you view the balance between having enough hydroxychloroquine for patients with lupus or other rheumatic diseases and its use in COVID-19 patients?

A: We want to reassure patients that hydroxychloroquine will be available, and there is no reason to hoard the drug or to worry excessively about being unable to obtain it. Efforts to increase production by Mylan, Teva, Sanofi, Novartis, and other manufacturers of hydroxychloroquine should really help out.

Q: Are there pharmacy restrictions on prescription amounts?

A: This is not universal at this time, but some institutions are cutting back and offering only 1-month supplies.
 

Colchicine COVID-19 trial underway

Dr. Pillinger, of NYU Langone Health, explored the COLCORONA study of colchicine as a treatment for people infected with COVID-19 and the worry that shortage concerns may arise for it, too. 

Q: What is the general availability of colchicine and its susceptibility to shortage?

A: There are two major manufacturers of colchicine in the United States, Takeda and Hikma, who together manufacture the majority of the drug.

The greatest use of colchicine in the United States is for gout, which affects approximately 4 million Americans, but the drug is not used chronically, so a much smaller number of patients are using colchicine at any one time. Colchicine is also used for other inflammatory conditions, primarily calcium pyrophosphate crystal disease and familial Mediterranean fever (FMF is rare in the United States). Cardiologists also regularly prescribe colchicine in pericarditis for short-term use. Physicians may use it off label for other purposes, too.

Overall, the number of patients using colchicine is much larger than that for the use of hydroxychloroquine, for example, suggesting that the immediate risk of shortage could be lower. However, if individuals started using it off label, or prescribing inappropriately for the COVID-19 indication, the supply would rapidly run short.
 

Q: What other points are there to consider regarding the use of colchicine to treat COVID-19?

A: There is no evidence – zero – that colchicine has any benefit for COVID-19, not even case reports. There is some rationale that it might be beneficial, but that is exactly why the COLCORONA trial would be logical to try.

The COLCORONA trial is exactly the kind of trial that would be needed for assessing colchicine, and it is big enough and happening quickly enough to get an answer. But if people start to use colchicine off label, we may never know the truth.

While colchicine can be used safely in most people, it can be very problematic and requires an experienced doctor’s supervision. Overdoses can be fatal, and colchicine interacts with many drugs, all of which require dose adjustment and some of which must be stopped in order to use colchicine – it isn’t candy. Some of the other drugs being looked at for COVID-19 in fact may interact with colchicine.

Colchicine must also be dose adjusted for kidney disease, and, in some of the COVID-19 patients, kidney function changes rapidly. So again, its use would require expert supervision even if there were evidence for its utility.

The side effects of colchicine, if mis-dosed, can be very unpleasant, including nausea, vomiting, and diarrhea. Even at the apparent right dose, some people will get these side effects, so colchicine has to be something that works to make the risk/benefit ratio worth it.

Some preparations of colchicine are made combined with probenecid, a gout drug. This is even more problematic because probenecid can raise the level of drugs excreted by the kidney and could affect other treatments.

So in sum, what may be a good idea in theory can turn out to be a disastrous idea in practice, and here we have nothing but theory. This is not an agent to use randomly; the studies will be rushed out quickly and hopefully will give us the knowledge to know what to do.

Dr. Izmirly and Dr. Buyon said they have research grants with the National Institutes of Health to study hydroxychloroquine in patients with lupus and in anti–SSA/Ro-positive pregnant women with a previous child with congenital heart block. Dr. Pillinger reports that he has an investigator-initiated grant from Hikma to study colchicine in osteoarthritis.

[email protected]

This article was reformatted on 3/30/2020 for clarity. 

Despite highly effective antiretroviral therapy, HIV still shortens life expectancy by 9 years and healthy life expectancy free of comorbidities 16 years, according to a review of HIV patients and matched controls at Kaiser Permanente facilities in California and the mid-Atlantic states during 2000-2016.

M. Alexander Otto/MDedge News

The good news is that starting antiretroviral therapy (ART) when CD4 counts are 500 cells/mm³ or higher closes the mortality gap. People who do so can expect to live into their mid-80s, the same as people without HIV, and the years they can expect to be free of diabetes and cancer is catching up to uninfected people, although the gap for other comorbidities hasn’t changed and the overall comorbidity gap remains 16 years, according to the report, which was presented at the Conference on Retroviruses & Opportunistic Infections

“We were excited about finding no difference in lifespan for people starting ART with high CD4 counts, but we were surprised by how wide the gap was for the number of comorbidity free years. Greater attention to comorbidity prevention is needed,” said study lead Julia Marcus, PhD, an infectious disease epidemiologist and assistant professor of population medicine at Harvard Medical School, Boston.

The team estimated the average number of total and comorbidity-free years of life remaining at age 21 for 39,000 people with HIV who were matched 1:10 with 387,767 uninfected adults by sex, race/ethnicity, year, and medical center.

Overall, adults with HIV could expect to live until they were 77 years old, versus 86 years for people without HIV, during 2014-2016. It’s a large improvement over the 22 year gap during 2000-2003, when the numbers were 59 versus 81 years, respectively, Dr. Marcus reported at the virtual meeting, which was scheduled to be in Boston, but held online this year because of concerns about spreading the COVID-19 virus.

But the overall comorbidity gap didn’t budge during 2000-2016. People with HIV during 2014-2016 could expect to be comorbidity free until age 36 years, versus 52 years for the general population, the same 16-year difference during 2000-2003, when the numbers were age 32 versus age 48 years.

During 2014-2016, liver disease came 24 years sooner with HIV, and chronic kidney disease 17 years, chronic lung disease 16 years, cancer 9 years, and diabetes and cancer both 8 years sooner. Early ART didn’t narrow the gap for most comorbidities. Dr. Marcus didn’t address the reasons for the differences, except to note that “smoking rates were definitely higher among people with HIV.”

The results weren’t broken down by sex, but the majority of subjects, 88%, were men. The mean age was 41 years, and about half were white, with most of the rest either black or Hispanic. Transmission was among men who have sex with men in 70% of the cases, heterosexual sex in 20%, and IV drug accounted for the rest. Almost a third of the subjects started ART with CD4 counts at or above 500 cells/mm³.

Dr. Marcus said the results are likely generalizable to most insured people with HIV, but also that comorbidity screening might be higher in the HIV population, which could have affected the results.

The work was funded by the National Institutes of Health. Dr. Marcus is an adviser for Gilead.

[email protected]

SOURCE: Marcus JL et al. CROI 2020. Abstract 151.

Despite highly effective antiretroviral therapy, HIV still shortens life expectancy by 9 years and healthy life expectancy free of comorbidities 16 years, according to a review of HIV patients and matched controls at Kaiser Permanente facilities in California and the mid-Atlantic states during 2000-2016.

M. Alexander Otto/MDedge News

The good news is that starting antiretroviral therapy (ART) when CD4 counts are 500 cells/mm³ or higher closes the mortality gap. People who do so can expect to live into their mid-80s, the same as people without HIV, and the years they can expect to be free of diabetes and cancer is catching up to uninfected people, although the gap for other comorbidities hasn’t changed and the overall comorbidity gap remains 16 years, according to the report, which was presented at the Conference on Retroviruses & Opportunistic Infections

“We were excited about finding no difference in lifespan for people starting ART with high CD4 counts, but we were surprised by how wide the gap was for the number of comorbidity free years. Greater attention to comorbidity prevention is needed,” said study lead Julia Marcus, PhD, an infectious disease epidemiologist and assistant professor of population medicine at Harvard Medical School, Boston.

The team estimated the average number of total and comorbidity-free years of life remaining at age 21 for 39,000 people with HIV who were matched 1:10 with 387,767 uninfected adults by sex, race/ethnicity, year, and medical center.

Overall, adults with HIV could expect to live until they were 77 years old, versus 86 years for people without HIV, during 2014-2016. It’s a large improvement over the 22 year gap during 2000-2003, when the numbers were 59 versus 81 years, respectively, Dr. Marcus reported at the virtual meeting, which was scheduled to be in Boston, but held online this year because of concerns about spreading the COVID-19 virus.

But the overall comorbidity gap didn’t budge during 2000-2016. People with HIV during 2014-2016 could expect to be comorbidity free until age 36 years, versus 52 years for the general population, the same 16-year difference during 2000-2003, when the numbers were age 32 versus age 48 years.

During 2014-2016, liver disease came 24 years sooner with HIV, and chronic kidney disease 17 years, chronic lung disease 16 years, cancer 9 years, and diabetes and cancer both 8 years sooner. Early ART didn’t narrow the gap for most comorbidities. Dr. Marcus didn’t address the reasons for the differences, except to note that “smoking rates were definitely higher among people with HIV.”

The results weren’t broken down by sex, but the majority of subjects, 88%, were men. The mean age was 41 years, and about half were white, with most of the rest either black or Hispanic. Transmission was among men who have sex with men in 70% of the cases, heterosexual sex in 20%, and IV drug accounted for the rest. Almost a third of the subjects started ART with CD4 counts at or above 500 cells/mm³.

Dr. Marcus said the results are likely generalizable to most insured people with HIV, but also that comorbidity screening might be higher in the HIV population, which could have affected the results.

The work was funded by the National Institutes of Health. Dr. Marcus is an adviser for Gilead.

[email protected]

SOURCE: Marcus JL et al. CROI 2020. Abstract 151.

Despite highly effective antiretroviral therapy, HIV still shortens life expectancy by 9 years and healthy life expectancy free of comorbidities 16 years, according to a review of HIV patients and matched controls at Kaiser Permanente facilities in California and the mid-Atlantic states during 2000-2016.

M. Alexander Otto/MDedge News

The good news is that starting antiretroviral therapy (ART) when CD4 counts are 500 cells/mm³ or higher closes the mortality gap. People who do so can expect to live into their mid-80s, the same as people without HIV, and the years they can expect to be free of diabetes and cancer is catching up to uninfected people, although the gap for other comorbidities hasn’t changed and the overall comorbidity gap remains 16 years, according to the report, which was presented at the Conference on Retroviruses & Opportunistic Infections

“We were excited about finding no difference in lifespan for people starting ART with high CD4 counts, but we were surprised by how wide the gap was for the number of comorbidity free years. Greater attention to comorbidity prevention is needed,” said study lead Julia Marcus, PhD, an infectious disease epidemiologist and assistant professor of population medicine at Harvard Medical School, Boston.

The team estimated the average number of total and comorbidity-free years of life remaining at age 21 for 39,000 people with HIV who were matched 1:10 with 387,767 uninfected adults by sex, race/ethnicity, year, and medical center.

Overall, adults with HIV could expect to live until they were 77 years old, versus 86 years for people without HIV, during 2014-2016. It’s a large improvement over the 22 year gap during 2000-2003, when the numbers were 59 versus 81 years, respectively, Dr. Marcus reported at the virtual meeting, which was scheduled to be in Boston, but held online this year because of concerns about spreading the COVID-19 virus.

But the overall comorbidity gap didn’t budge during 2000-2016. People with HIV during 2014-2016 could expect to be comorbidity free until age 36 years, versus 52 years for the general population, the same 16-year difference during 2000-2003, when the numbers were age 32 versus age 48 years.

During 2014-2016, liver disease came 24 years sooner with HIV, and chronic kidney disease 17 years, chronic lung disease 16 years, cancer 9 years, and diabetes and cancer both 8 years sooner. Early ART didn’t narrow the gap for most comorbidities. Dr. Marcus didn’t address the reasons for the differences, except to note that “smoking rates were definitely higher among people with HIV.”

The results weren’t broken down by sex, but the majority of subjects, 88%, were men. The mean age was 41 years, and about half were white, with most of the rest either black or Hispanic. Transmission was among men who have sex with men in 70% of the cases, heterosexual sex in 20%, and IV drug accounted for the rest. Almost a third of the subjects started ART with CD4 counts at or above 500 cells/mm³.

Dr. Marcus said the results are likely generalizable to most insured people with HIV, but also that comorbidity screening might be higher in the HIV population, which could have affected the results.

The work was funded by the National Institutes of Health. Dr. Marcus is an adviser for Gilead.

[email protected]

SOURCE: Marcus JL et al. CROI 2020. Abstract 151.

Physicians were concerned about the safety of their loved ones and themselves and pessimistic about how those outside of the medical community will respond to the pandemic, according to a survey.

One positive finding from the physicians who participated in this survey March 19-20 was that the availability of COVID-19 test kits has more than doubled since late February.

Reported access to test kits went from 31% in the first wave of a series of surveys (Jan. 31–Feb. 4), down to 20% in the second (Feb. 26-27), and then jumped to 67% by the third wave (March 19-20), InCrowd reported March 26.

Views on several other COVID-related topics were negative among the majority of responding physicians – all of whom had or were currently treating 20 or more patients with flu-like symptoms at the time of the survey.

“Their frustrations and concerns about their ability to protect themselves while meeting upcoming patient care levels has increased significantly in the last 3 months,” Daniel S. Fitzgerald, CEO and president of InCrowd, said in a written statement.

In the third wave, 78% of respondents were “concerned for the safety of loved ones due to my exposure as a physician to COVID-19” and only 16% believed that their facility was “staffed adequately to treat the influx of patients anticipated in the next 30 days,” InCrowd said.

One primary care physician from California elaborated on the issue of safety equipment: “First, [the CDC] said we need N95 masks and other masks would not protect us. As those are running out then they said just use regular surgical masks. Now they are saying use bandannas and scarves! It’s like they don’t care about the safety of the people who will be treating the ill! We don’t want to bring it home to our families!”

“Overall, morale appears low, with few optimistic about the efficacy of public-private collaboration (21%), their own safety given current PPE [personal protective equipment] supply (13%), and the U.S.’s ability to ‘flatten the curve’ (12%),” InCrowd noted in the report.

The first two waves each had 150 respondents, but the number increased to 263 for wave 3, with similar proportions – about 50% emergency medicine or critical care specialists, 25% pediatricians, and 25% primary care physicians – in all three.

[email protected]

Physicians were concerned about the safety of their loved ones and themselves and pessimistic about how those outside of the medical community will respond to the pandemic, according to a survey.

One positive finding from the physicians who participated in this survey March 19-20 was that the availability of COVID-19 test kits has more than doubled since late February.

Reported access to test kits went from 31% in the first wave of a series of surveys (Jan. 31–Feb. 4), down to 20% in the second (Feb. 26-27), and then jumped to 67% by the third wave (March 19-20), InCrowd reported March 26.

Views on several other COVID-related topics were negative among the majority of responding physicians – all of whom had or were currently treating 20 or more patients with flu-like symptoms at the time of the survey.

“Their frustrations and concerns about their ability to protect themselves while meeting upcoming patient care levels has increased significantly in the last 3 months,” Daniel S. Fitzgerald, CEO and president of InCrowd, said in a written statement.

In the third wave, 78% of respondents were “concerned for the safety of loved ones due to my exposure as a physician to COVID-19” and only 16% believed that their facility was “staffed adequately to treat the influx of patients anticipated in the next 30 days,” InCrowd said.

One primary care physician from California elaborated on the issue of safety equipment: “First, [the CDC] said we need N95 masks and other masks would not protect us. As those are running out then they said just use regular surgical masks. Now they are saying use bandannas and scarves! It’s like they don’t care about the safety of the people who will be treating the ill! We don’t want to bring it home to our families!”

“Overall, morale appears low, with few optimistic about the efficacy of public-private collaboration (21%), their own safety given current PPE [personal protective equipment] supply (13%), and the U.S.’s ability to ‘flatten the curve’ (12%),” InCrowd noted in the report.

The first two waves each had 150 respondents, but the number increased to 263 for wave 3, with similar proportions – about 50% emergency medicine or critical care specialists, 25% pediatricians, and 25% primary care physicians – in all three.

[email protected]

Physicians were concerned about the safety of their loved ones and themselves and pessimistic about how those outside of the medical community will respond to the pandemic, according to a survey.

One positive finding from the physicians who participated in this survey March 19-20 was that the availability of COVID-19 test kits has more than doubled since late February.

Reported access to test kits went from 31% in the first wave of a series of surveys (Jan. 31–Feb. 4), down to 20% in the second (Feb. 26-27), and then jumped to 67% by the third wave (March 19-20), InCrowd reported March 26.

Views on several other COVID-related topics were negative among the majority of responding physicians – all of whom had or were currently treating 20 or more patients with flu-like symptoms at the time of the survey.

“Their frustrations and concerns about their ability to protect themselves while meeting upcoming patient care levels has increased significantly in the last 3 months,” Daniel S. Fitzgerald, CEO and president of InCrowd, said in a written statement.

In the third wave, 78% of respondents were “concerned for the safety of loved ones due to my exposure as a physician to COVID-19” and only 16% believed that their facility was “staffed adequately to treat the influx of patients anticipated in the next 30 days,” InCrowd said.

One primary care physician from California elaborated on the issue of safety equipment: “First, [the CDC] said we need N95 masks and other masks would not protect us. As those are running out then they said just use regular surgical masks. Now they are saying use bandannas and scarves! It’s like they don’t care about the safety of the people who will be treating the ill! We don’t want to bring it home to our families!”

“Overall, morale appears low, with few optimistic about the efficacy of public-private collaboration (21%), their own safety given current PPE [personal protective equipment] supply (13%), and the U.S.’s ability to ‘flatten the curve’ (12%),” InCrowd noted in the report.

The first two waves each had 150 respondents, but the number increased to 263 for wave 3, with similar proportions – about 50% emergency medicine or critical care specialists, 25% pediatricians, and 25% primary care physicians – in all three.

[email protected]