Infectious Diseases

View Answers

View Answers

View Answers

The Diagnosis: Disseminated Fusariosis  

Histologic evaluation of the punch biopsy demonstrated thrombosed vessels in the deep dermis and along fibrous septae of subcutaneous tissue, as well as delicate, thin-walled, branching hyphae with vesicular swellings (Figure). The hyphae were present within the vascular thrombi and extended into surrounding tissue. The fungal tissue culture eventually grew scant Fusarium. At the time of biopsy, there was a high index of suspicion for fungal infection, which supported the decision to empirically treat with anidulafungin and voriconazole.  

Differentiating the diagnosis in this case was done primarily with histopathology. Although Aspergillus also has slender hyphae, it lacks the vesicular swellings characteristic of fusariosis. Disseminated candidiasis would demonstrate budding yeast and pseudohyphae in the dermis. Ecthyma gangrenosum histologically presents as necrotizing hemorrhagic vasculitis with gram-negative rods in the walls of deeper vessels, characteristically sparing the intima. Leukemia cutis histologically varies but would display a neoplastic infiltrate of atypical monocytoid cells with nuclear pleomorphism.  

Our patient had been treated with palliative chemotherapy as a salvage regimen with idarubicin and cytarabine. She had persistent pancytopenia despite granulocyte-macrophage colony-stimulating factor therapy. The mortality rate for disseminated Fusarium infection approaches 100% when risk factors such as angiotropism and prolonged neutropenia are present.^1,2 Additionally, our patient's susceptibility profile subsequently demonstrated an elevated minimum inhibitory concentration to amphotericin B, itraconazole, voriconazole, and posaconazole. The neutropenia and Fusarium infection were not responsive to treatment. She was discharged on palliative voriconazole with home hospice care.  

Fusarium species are soil-dwelling saprophytes and important plant pathogens that have increasingly emerged as rare but notable causes of morbidity and mortality in immunocompromised patients.^1-3 More specifically, Fusarium infection is most commonly observed in patients with hematologic malignancy complicated by persistent neutropenia. The 3 most frequently encountered Fusarium species in human disease are Fusarium solani, Fusarium oxysporum, and Fusarium moniliforme, with F solani being the most virulent.^1,2 Infection with Fusarium may manifest as a broad range of presentations depending on the route of entry, such as endophthalmitis, sinusitis, pneumonia, and cutaneous lesions.¹ Disseminated infection is marked by skin lesions or positive blood cultures for Fusarium.³ This fungus is notorious for its limited susceptibility profile.¹ It requires systemic antifungal medications such as triazoles and amphotericin B. Fusarium is most susceptible in vitro to amphotericin B but often requires toxic dosages to be effective in decreasing fungal load.^2,3 The high mortality rate of disseminated fusariosis further emphasizes that prevention is an important component to protecting high-risk patients. Keeping patients in rooms with high-efficiency particulate arresting filters and limiting exposure to unsanitized tap water faucets can help decrease exposure; however, reducing immunosuppression and improving neutropenia are the most effective ways to prevent fusariosis.¹ Although skin breakdown can facilitate the spread of infection, it has been observed that immunosuppressed individuals do not necessarily have this finding.⁴ 

This case emphasizes the importance of considering disseminated fusariosis in patients with hematologic malignancy or other immunosuppressed conditions. The most important factors that should raise clinical suspicion are persistent neutropenia and recent corticosteroid therapy.¹ A clinical picture that suggests fungal infection should warrant consideration of prophylactic treatment as well as tissue and blood cultures to determine species and susceptibility.  
 

The Diagnosis: Disseminated Fusariosis  

Histologic evaluation of the punch biopsy demonstrated thrombosed vessels in the deep dermis and along fibrous septae of subcutaneous tissue, as well as delicate, thin-walled, branching hyphae with vesicular swellings (Figure). The hyphae were present within the vascular thrombi and extended into surrounding tissue. The fungal tissue culture eventually grew scant Fusarium. At the time of biopsy, there was a high index of suspicion for fungal infection, which supported the decision to empirically treat with anidulafungin and voriconazole.  

Differentiating the diagnosis in this case was done primarily with histopathology. Although Aspergillus also has slender hyphae, it lacks the vesicular swellings characteristic of fusariosis. Disseminated candidiasis would demonstrate budding yeast and pseudohyphae in the dermis. Ecthyma gangrenosum histologically presents as necrotizing hemorrhagic vasculitis with gram-negative rods in the walls of deeper vessels, characteristically sparing the intima. Leukemia cutis histologically varies but would display a neoplastic infiltrate of atypical monocytoid cells with nuclear pleomorphism.  

Our patient had been treated with palliative chemotherapy as a salvage regimen with idarubicin and cytarabine. She had persistent pancytopenia despite granulocyte-macrophage colony-stimulating factor therapy. The mortality rate for disseminated Fusarium infection approaches 100% when risk factors such as angiotropism and prolonged neutropenia are present.^1,2 Additionally, our patient's susceptibility profile subsequently demonstrated an elevated minimum inhibitory concentration to amphotericin B, itraconazole, voriconazole, and posaconazole. The neutropenia and Fusarium infection were not responsive to treatment. She was discharged on palliative voriconazole with home hospice care.  

Fusarium species are soil-dwelling saprophytes and important plant pathogens that have increasingly emerged as rare but notable causes of morbidity and mortality in immunocompromised patients.^1-3 More specifically, Fusarium infection is most commonly observed in patients with hematologic malignancy complicated by persistent neutropenia. The 3 most frequently encountered Fusarium species in human disease are Fusarium solani, Fusarium oxysporum, and Fusarium moniliforme, with F solani being the most virulent.^1,2 Infection with Fusarium may manifest as a broad range of presentations depending on the route of entry, such as endophthalmitis, sinusitis, pneumonia, and cutaneous lesions.¹ Disseminated infection is marked by skin lesions or positive blood cultures for Fusarium.³ This fungus is notorious for its limited susceptibility profile.¹ It requires systemic antifungal medications such as triazoles and amphotericin B. Fusarium is most susceptible in vitro to amphotericin B but often requires toxic dosages to be effective in decreasing fungal load.^2,3 The high mortality rate of disseminated fusariosis further emphasizes that prevention is an important component to protecting high-risk patients. Keeping patients in rooms with high-efficiency particulate arresting filters and limiting exposure to unsanitized tap water faucets can help decrease exposure; however, reducing immunosuppression and improving neutropenia are the most effective ways to prevent fusariosis.¹ Although skin breakdown can facilitate the spread of infection, it has been observed that immunosuppressed individuals do not necessarily have this finding.⁴ 

This case emphasizes the importance of considering disseminated fusariosis in patients with hematologic malignancy or other immunosuppressed conditions. The most important factors that should raise clinical suspicion are persistent neutropenia and recent corticosteroid therapy.¹ A clinical picture that suggests fungal infection should warrant consideration of prophylactic treatment as well as tissue and blood cultures to determine species and susceptibility.  
 

The Diagnosis: Disseminated Fusariosis  

Histologic evaluation of the punch biopsy demonstrated thrombosed vessels in the deep dermis and along fibrous septae of subcutaneous tissue, as well as delicate, thin-walled, branching hyphae with vesicular swellings (Figure). The hyphae were present within the vascular thrombi and extended into surrounding tissue. The fungal tissue culture eventually grew scant Fusarium. At the time of biopsy, there was a high index of suspicion for fungal infection, which supported the decision to empirically treat with anidulafungin and voriconazole.  

Differentiating the diagnosis in this case was done primarily with histopathology. Although Aspergillus also has slender hyphae, it lacks the vesicular swellings characteristic of fusariosis. Disseminated candidiasis would demonstrate budding yeast and pseudohyphae in the dermis. Ecthyma gangrenosum histologically presents as necrotizing hemorrhagic vasculitis with gram-negative rods in the walls of deeper vessels, characteristically sparing the intima. Leukemia cutis histologically varies but would display a neoplastic infiltrate of atypical monocytoid cells with nuclear pleomorphism.  

Our patient had been treated with palliative chemotherapy as a salvage regimen with idarubicin and cytarabine. She had persistent pancytopenia despite granulocyte-macrophage colony-stimulating factor therapy. The mortality rate for disseminated Fusarium infection approaches 100% when risk factors such as angiotropism and prolonged neutropenia are present.^1,2 Additionally, our patient's susceptibility profile subsequently demonstrated an elevated minimum inhibitory concentration to amphotericin B, itraconazole, voriconazole, and posaconazole. The neutropenia and Fusarium infection were not responsive to treatment. She was discharged on palliative voriconazole with home hospice care.  

Fusarium species are soil-dwelling saprophytes and important plant pathogens that have increasingly emerged as rare but notable causes of morbidity and mortality in immunocompromised patients.^1-3 More specifically, Fusarium infection is most commonly observed in patients with hematologic malignancy complicated by persistent neutropenia. The 3 most frequently encountered Fusarium species in human disease are Fusarium solani, Fusarium oxysporum, and Fusarium moniliforme, with F solani being the most virulent.^1,2 Infection with Fusarium may manifest as a broad range of presentations depending on the route of entry, such as endophthalmitis, sinusitis, pneumonia, and cutaneous lesions.¹ Disseminated infection is marked by skin lesions or positive blood cultures for Fusarium.³ This fungus is notorious for its limited susceptibility profile.¹ It requires systemic antifungal medications such as triazoles and amphotericin B. Fusarium is most susceptible in vitro to amphotericin B but often requires toxic dosages to be effective in decreasing fungal load.^2,3 The high mortality rate of disseminated fusariosis further emphasizes that prevention is an important component to protecting high-risk patients. Keeping patients in rooms with high-efficiency particulate arresting filters and limiting exposure to unsanitized tap water faucets can help decrease exposure; however, reducing immunosuppression and improving neutropenia are the most effective ways to prevent fusariosis.¹ Although skin breakdown can facilitate the spread of infection, it has been observed that immunosuppressed individuals do not necessarily have this finding.⁴ 

This case emphasizes the importance of considering disseminated fusariosis in patients with hematologic malignancy or other immunosuppressed conditions. The most important factors that should raise clinical suspicion are persistent neutropenia and recent corticosteroid therapy.¹ A clinical picture that suggests fungal infection should warrant consideration of prophylactic treatment as well as tissue and blood cultures to determine species and susceptibility.  
 

For patients with chronic hepatitis B (HBV), an aspirin a day could keep hepatocellular carcinoma (HCC) away, according to a cohort study of more than 10,000 patients in Taiwan.

jimdeli/Fotolia

Sixteen years of data showed that daily aspirin therapy reduced the risk of HBV-related HCC by 29%, reported lead author Teng-Yu Lee, MD, PhD, of Taichung (Taiwan) Veterans General Hospital and his colleagues. Analysis also showed that antiviral nucleos(t)ide analogue therapy and statin use were independently associated with reduced risk of HCC, whereas older age, cirrhosis, and male sex increased risk.

“Therapy with [nucleos(t)ide analogues] is associated with reductions in HCC risk, but the risk is not erased,” the investigators wrote in JAMA Internal Medicine. “Therefore, using only [nucleos(t)ide analogue] therapy may not be enough for HCC prevention. Antiviral therapy is not indicated in most HBV carriers, so another effective way of reducing HCC risk needs to be developed.”

Previous studies have shown that aspirin can reduce the risk of colorectal cancer; however, data supporting aspirin for HCC prevention are limited to a few animal models and human studies, the latter of which are statistically unreliable.

“Therefore, we conducted a nationwide cohort study to evaluate the association of daily aspirin therapy with HBV-related HCC,” the investigators wrote.

They screened 204,507 patients with HBV included in the Taiwanese National Health Insurance Research Database (NHIRD) between 1997 and 2012, first excluding any with confounding conditions, such as hepatitis C infection or alcoholic liver disease. Next, 2,123 patients were identified who had taken aspirin for 90 days or longer. Finally, these cases were randomly matched with 8,492 control patients with HBV who had never received antiplatelet therapy. The main measured outcome was diagnosis with HCC. Patients were followed until this diagnosis was made, death occurred, or the end of the study period.

Analysis showed that most patients were male (72.4%) and took aspirin for about 4 years, usually prescribed for cardiovascular disease risk factors. Almost all patients in the treatment group (98%) received an aspirin dose of 100 mg or less.

After 5 years, the cumulative incidence of HCC in the aspirin group was 5.20% versus 7.87% in the control group (P less than .001). Multivariable analysis revealed that daily aspirin was associated with a significant risk reduction of 29% (HR 0.71; P less than .001), as were nucleos(t)ide analogues and statins, which lowered risk by 46% and 38%, respectively. In contrast, risk increased with older age at the rate of 1% per year, male sex carried an additional risk of 75%, and liver cirrhosis was associated with a 2.89-fold risk increase.

“In the present study, we report that daily aspirin therapy was associated with a reduced incidence of HCC in patients with [chronic hepatitis B],” the investigators wrote. “Our findings may be of help in future efforts to further improve the chemoprevention of HBV-related HCC, and a proof-of-concept study is thus warranted.”

The investigators described several mechanisms that may have contribute to the possible risk reduction provided by aspirin. For one, aspirin inhibits platelet activation, which is associated with development of HBV-related liver disease. Additional benefit may come from induction of HCC cell apoptosis, control of tumor growth, reduced liver fibrosis, and increased liver regeneration, all of which have been associated with aspirin in rodent models.

“Hepatitis B virus–related HCC is generally a consequence of chronic inflammation due to hepatitis, fibrosis, dysplasia, and tumor growth,” the investigators wrote, suggesting that aspirin-related reductions in inflammation could also explain reduced neoplastic activity.

To assess for increased risk of peptic ulcers secondary to aspirin, the investigators performed a subanalysis of peptic ulcer bleeding. These results showed that rates of peptic ulcer bleeding, at around 5%-6%, were similar between the aspirin group and the control group. Among other variables, cirrhosis didn’t significantly affect rates of peptic ulcer bleeding, and aspirin users had similar rates of peptic ulcer bleeding regardless of HBV status. Because of the study design, however, the investigators cautioned that these analyses could underestimate ulcer risk because patients who could not tolerate aspirin for at least 90 days were excluded from the study.

Although statins stood out as another possible risk reducer, the investigators noted that “randomized clinical trials are required to confirm the chemopreventive effect of statins.”

Similarly, the investigators suggested that a prospective trial is needed before aspirin can be adopted as an HCC preventive.

The study was funded by the Ministry of Science and Technology, National Health Research Institutes, and Taichung (Taiwan) Veterans General Hospital, Taiwan. One author reported financial compensation from Gilead and Bristol-Myers Squibb.

SOURCE: Lee T-Y et al. JAMA Intern Med. 2019 Mar 18. doi:10.1001/jamainternmed.2018.8342.

For patients with chronic hepatitis B (HBV), an aspirin a day could keep hepatocellular carcinoma (HCC) away, according to a cohort study of more than 10,000 patients in Taiwan.

jimdeli/Fotolia

Sixteen years of data showed that daily aspirin therapy reduced the risk of HBV-related HCC by 29%, reported lead author Teng-Yu Lee, MD, PhD, of Taichung (Taiwan) Veterans General Hospital and his colleagues. Analysis also showed that antiviral nucleos(t)ide analogue therapy and statin use were independently associated with reduced risk of HCC, whereas older age, cirrhosis, and male sex increased risk.

“Therapy with [nucleos(t)ide analogues] is associated with reductions in HCC risk, but the risk is not erased,” the investigators wrote in JAMA Internal Medicine. “Therefore, using only [nucleos(t)ide analogue] therapy may not be enough for HCC prevention. Antiviral therapy is not indicated in most HBV carriers, so another effective way of reducing HCC risk needs to be developed.”

Previous studies have shown that aspirin can reduce the risk of colorectal cancer; however, data supporting aspirin for HCC prevention are limited to a few animal models and human studies, the latter of which are statistically unreliable.

“Therefore, we conducted a nationwide cohort study to evaluate the association of daily aspirin therapy with HBV-related HCC,” the investigators wrote.

They screened 204,507 patients with HBV included in the Taiwanese National Health Insurance Research Database (NHIRD) between 1997 and 2012, first excluding any with confounding conditions, such as hepatitis C infection or alcoholic liver disease. Next, 2,123 patients were identified who had taken aspirin for 90 days or longer. Finally, these cases were randomly matched with 8,492 control patients with HBV who had never received antiplatelet therapy. The main measured outcome was diagnosis with HCC. Patients were followed until this diagnosis was made, death occurred, or the end of the study period.

Analysis showed that most patients were male (72.4%) and took aspirin for about 4 years, usually prescribed for cardiovascular disease risk factors. Almost all patients in the treatment group (98%) received an aspirin dose of 100 mg or less.

After 5 years, the cumulative incidence of HCC in the aspirin group was 5.20% versus 7.87% in the control group (P less than .001). Multivariable analysis revealed that daily aspirin was associated with a significant risk reduction of 29% (HR 0.71; P less than .001), as were nucleos(t)ide analogues and statins, which lowered risk by 46% and 38%, respectively. In contrast, risk increased with older age at the rate of 1% per year, male sex carried an additional risk of 75%, and liver cirrhosis was associated with a 2.89-fold risk increase.

“In the present study, we report that daily aspirin therapy was associated with a reduced incidence of HCC in patients with [chronic hepatitis B],” the investigators wrote. “Our findings may be of help in future efforts to further improve the chemoprevention of HBV-related HCC, and a proof-of-concept study is thus warranted.”

The investigators described several mechanisms that may have contribute to the possible risk reduction provided by aspirin. For one, aspirin inhibits platelet activation, which is associated with development of HBV-related liver disease. Additional benefit may come from induction of HCC cell apoptosis, control of tumor growth, reduced liver fibrosis, and increased liver regeneration, all of which have been associated with aspirin in rodent models.

“Hepatitis B virus–related HCC is generally a consequence of chronic inflammation due to hepatitis, fibrosis, dysplasia, and tumor growth,” the investigators wrote, suggesting that aspirin-related reductions in inflammation could also explain reduced neoplastic activity.

To assess for increased risk of peptic ulcers secondary to aspirin, the investigators performed a subanalysis of peptic ulcer bleeding. These results showed that rates of peptic ulcer bleeding, at around 5%-6%, were similar between the aspirin group and the control group. Among other variables, cirrhosis didn’t significantly affect rates of peptic ulcer bleeding, and aspirin users had similar rates of peptic ulcer bleeding regardless of HBV status. Because of the study design, however, the investigators cautioned that these analyses could underestimate ulcer risk because patients who could not tolerate aspirin for at least 90 days were excluded from the study.

Although statins stood out as another possible risk reducer, the investigators noted that “randomized clinical trials are required to confirm the chemopreventive effect of statins.”

Similarly, the investigators suggested that a prospective trial is needed before aspirin can be adopted as an HCC preventive.

The study was funded by the Ministry of Science and Technology, National Health Research Institutes, and Taichung (Taiwan) Veterans General Hospital, Taiwan. One author reported financial compensation from Gilead and Bristol-Myers Squibb.

SOURCE: Lee T-Y et al. JAMA Intern Med. 2019 Mar 18. doi:10.1001/jamainternmed.2018.8342.

For patients with chronic hepatitis B (HBV), an aspirin a day could keep hepatocellular carcinoma (HCC) away, according to a cohort study of more than 10,000 patients in Taiwan.

jimdeli/Fotolia

Sixteen years of data showed that daily aspirin therapy reduced the risk of HBV-related HCC by 29%, reported lead author Teng-Yu Lee, MD, PhD, of Taichung (Taiwan) Veterans General Hospital and his colleagues. Analysis also showed that antiviral nucleos(t)ide analogue therapy and statin use were independently associated with reduced risk of HCC, whereas older age, cirrhosis, and male sex increased risk.

“Therapy with [nucleos(t)ide analogues] is associated with reductions in HCC risk, but the risk is not erased,” the investigators wrote in JAMA Internal Medicine. “Therefore, using only [nucleos(t)ide analogue] therapy may not be enough for HCC prevention. Antiviral therapy is not indicated in most HBV carriers, so another effective way of reducing HCC risk needs to be developed.”

Previous studies have shown that aspirin can reduce the risk of colorectal cancer; however, data supporting aspirin for HCC prevention are limited to a few animal models and human studies, the latter of which are statistically unreliable.

“Therefore, we conducted a nationwide cohort study to evaluate the association of daily aspirin therapy with HBV-related HCC,” the investigators wrote.

They screened 204,507 patients with HBV included in the Taiwanese National Health Insurance Research Database (NHIRD) between 1997 and 2012, first excluding any with confounding conditions, such as hepatitis C infection or alcoholic liver disease. Next, 2,123 patients were identified who had taken aspirin for 90 days or longer. Finally, these cases were randomly matched with 8,492 control patients with HBV who had never received antiplatelet therapy. The main measured outcome was diagnosis with HCC. Patients were followed until this diagnosis was made, death occurred, or the end of the study period.

Analysis showed that most patients were male (72.4%) and took aspirin for about 4 years, usually prescribed for cardiovascular disease risk factors. Almost all patients in the treatment group (98%) received an aspirin dose of 100 mg or less.

After 5 years, the cumulative incidence of HCC in the aspirin group was 5.20% versus 7.87% in the control group (P less than .001). Multivariable analysis revealed that daily aspirin was associated with a significant risk reduction of 29% (HR 0.71; P less than .001), as were nucleos(t)ide analogues and statins, which lowered risk by 46% and 38%, respectively. In contrast, risk increased with older age at the rate of 1% per year, male sex carried an additional risk of 75%, and liver cirrhosis was associated with a 2.89-fold risk increase.

“In the present study, we report that daily aspirin therapy was associated with a reduced incidence of HCC in patients with [chronic hepatitis B],” the investigators wrote. “Our findings may be of help in future efforts to further improve the chemoprevention of HBV-related HCC, and a proof-of-concept study is thus warranted.”

The investigators described several mechanisms that may have contribute to the possible risk reduction provided by aspirin. For one, aspirin inhibits platelet activation, which is associated with development of HBV-related liver disease. Additional benefit may come from induction of HCC cell apoptosis, control of tumor growth, reduced liver fibrosis, and increased liver regeneration, all of which have been associated with aspirin in rodent models.

“Hepatitis B virus–related HCC is generally a consequence of chronic inflammation due to hepatitis, fibrosis, dysplasia, and tumor growth,” the investigators wrote, suggesting that aspirin-related reductions in inflammation could also explain reduced neoplastic activity.

To assess for increased risk of peptic ulcers secondary to aspirin, the investigators performed a subanalysis of peptic ulcer bleeding. These results showed that rates of peptic ulcer bleeding, at around 5%-6%, were similar between the aspirin group and the control group. Among other variables, cirrhosis didn’t significantly affect rates of peptic ulcer bleeding, and aspirin users had similar rates of peptic ulcer bleeding regardless of HBV status. Because of the study design, however, the investigators cautioned that these analyses could underestimate ulcer risk because patients who could not tolerate aspirin for at least 90 days were excluded from the study.

Although statins stood out as another possible risk reducer, the investigators noted that “randomized clinical trials are required to confirm the chemopreventive effect of statins.”

Similarly, the investigators suggested that a prospective trial is needed before aspirin can be adopted as an HCC preventive.

The study was funded by the Ministry of Science and Technology, National Health Research Institutes, and Taichung (Taiwan) Veterans General Hospital, Taiwan. One author reported financial compensation from Gilead and Bristol-Myers Squibb.

SOURCE: Lee T-Y et al. JAMA Intern Med. 2019 Mar 18. doi:10.1001/jamainternmed.2018.8342.

The United States is now up to 314 confirmed cases of measles for 2019, with the count going up by 46 during the week ending March 21, according to the Centers for Disease Control and Prevention.

Despite those 46 new cases, the number of states with reported cases remains at 15, the CDC reported March 25.

For the fifth consecutive week the busiest outbreak was in Brooklyn, N.Y., which added 23 new cases. New York’s Rockland County, which is just north of New York City and has 46 confirmed cases for the year, is home to another of the six current outbreaks in the country, with the other four located in Washington (74 total cases for the state), Texas (14 cases), California (7 cases), and Illinois (6 cases). Other states with cases are Arizona, Colorado, Connecticut, Georgia, Kentucky, Missouri, New Hampshire, New Jersey, and Oregon, reported the CDC.

This year’s case total through less than 3 months is nearing the 372 that occurred in 2018, which was the second-worst year for measles in the last decade, but is still well off the 10-year high of 667 reported in 2014, the CDC said.

[email protected]

The United States is now up to 314 confirmed cases of measles for 2019, with the count going up by 46 during the week ending March 21, according to the Centers for Disease Control and Prevention.

Despite those 46 new cases, the number of states with reported cases remains at 15, the CDC reported March 25.

For the fifth consecutive week the busiest outbreak was in Brooklyn, N.Y., which added 23 new cases. New York’s Rockland County, which is just north of New York City and has 46 confirmed cases for the year, is home to another of the six current outbreaks in the country, with the other four located in Washington (74 total cases for the state), Texas (14 cases), California (7 cases), and Illinois (6 cases). Other states with cases are Arizona, Colorado, Connecticut, Georgia, Kentucky, Missouri, New Hampshire, New Jersey, and Oregon, reported the CDC.

This year’s case total through less than 3 months is nearing the 372 that occurred in 2018, which was the second-worst year for measles in the last decade, but is still well off the 10-year high of 667 reported in 2014, the CDC said.

[email protected]

The United States is now up to 314 confirmed cases of measles for 2019, with the count going up by 46 during the week ending March 21, according to the Centers for Disease Control and Prevention.

Despite those 46 new cases, the number of states with reported cases remains at 15, the CDC reported March 25.

For the fifth consecutive week the busiest outbreak was in Brooklyn, N.Y., which added 23 new cases. New York’s Rockland County, which is just north of New York City and has 46 confirmed cases for the year, is home to another of the six current outbreaks in the country, with the other four located in Washington (74 total cases for the state), Texas (14 cases), California (7 cases), and Illinois (6 cases). Other states with cases are Arizona, Colorado, Connecticut, Georgia, Kentucky, Missouri, New Hampshire, New Jersey, and Oregon, reported the CDC.

This year’s case total through less than 3 months is nearing the 372 that occurred in 2018, which was the second-worst year for measles in the last decade, but is still well off the 10-year high of 667 reported in 2014, the CDC said.

[email protected]

SEATTLE – A long-acting, injectable combination of the novel integrase inhibitor cabotegravir (CAB) and the second-generation nonnucleoside reverse transcriptase inhibitor rilpivirine (RPV) was noninferior to dolutegravir/abacavir/lamivudine (DTG/ABC/3TC) in one phase 3 study (FLAIR) and to three-drug oral antiretroviral therapy (ART) more broadly in the companion ATLAS phase 3 study. Patient acceptance of the injectable formulation was surprisingly high, although researchers admitted there was likely some selection bias because patients already interested in receiving an injection would have been predisposed to entering the trials.

Ca-ssis/Thinkstock

Still, the numbers were impressive: 99% of patients who received the intramuscular injection expressed more satisfaction with it than with their previous oral regimen in the FLAIR study, and 98% expressed a similar opinion in the ATLAS study. Circumstantial evidence also suggests there may be some demand, according to Joseph Eron, MD, professor of medicine at the University of North Carolina at Chapel Hill, who commented during a press conference at the Conference on Retroviruses & Opportunistic Infections. “These studies didn’t take a long time to accrue. People were very interested, so it wasn’t as if people had to go around and beat the bushes to try to find people [to participate],” said Dr. Eron, who was not an author on either report.

“My patients tell me that they like not having to worry about taking their pills every day. There may be some relief from the stigma of HIV. You don’t have to think about it,” Susan Swindells, MBBS, medical director of the Specialty Care Clinic at the University of Nebraska Medical Center in Omaha and first author of the ATLAS trial, said during the press conference.

There were some injection site reactions, but they were generally mild and most resolved within 7 days. In the ATLAS study, 75% of participants reported injection site pain, and 1% discontinued as a result. In the FLAIR study, 82% in the CAB/RPV arm experienced an injection site reaction, with a median duration of 3 days; 99% of reactions were grade 1 or 2.

Should the combination achieve regulatory approval, it remains to be seen how challenging it will be to manage patients with monthly injections and ensure they stick to the schedule. The injections must be administered by a health care provider.

“In terms of generalizability outside of the study, it would be a paradigm shift in our therapy,” Chloe Orkin, MBBCh, said at a press conference. Dr. Orkin is the first author on the FLAIR trial report and a consultant in HIV Medicine at Barts Health National Health Service Trust. She pointed to the example of injectable contraception. “It can be done. It’s just that we haven’t done it. It will require some thought,” Dr. Orkin added.

In the ATLAS study, 616 participants taking two nucleoside reverse transcriptase inhibitor (NRTIs) and an integrase inhibitor, a non-NRTI, or a protease inhibitor, were randomized 1:1 to continue their regimen (CART arm) or switch to CAB/RPV, following a 4-week safety monitoring period of oral CAB/RPV. After 48 weeks, 1.6% in the CAB/RPV arm and 1.0% in the CART arm had HIV-1 RNA greater than or equal to 50 copies/mL, which met the prespecified noninferiority margin. Of patients in the CAB/RPV arm, 93% had HIV-1 RNA less than 50 copies/mL at week 48 versus 95% in the CART arm, and the difference was not statistically significant. Grade 3 or 4 events were seen in 11% of CAB/RPV and 7% of CART patients.

The FLAIR study randomized 566 ART-naive patients to receive either CAB/RPV or DTG/ABC/3TC after a 20-week induction phase, followed by a 4-week safety monitoring period for those going into the CAB/RPV arm. At week 48, 2.1% in the CAB/RPV arm and 2.5% in the DTG/ABC/3TC arm had HIV-1 RNA greater than or equal to 50 copies/mL, which met the prespecified noninferiority margin, while 94% in the CAB/RPV arm and 93% in the DTG/ABC/3TC arm had HIV-1 RNA less than 50 copies/mL. Confirmed virologic failure occurred in four patients (1.4%) in the CAB/RPV arm, and three of those patients had mutations in the NNRTI+INSTI domains, while the fourth patient was not tested. Three failures occurred in the DTG/ABC/3TC arm, and none of those patients had INSTI resistance mutations. A total of 82% of CAB/RPV patients had injection site reactions, 99% of which were grade 1 or 2, and the median duration was 3 days.

The ATLAS and FLAIR studies were sponsored by ViiV. Janssen and GlaxoSmithKline were collaborators.

SOURCES: Swindells S et al. CROI 2019, Abstract 139 LB. Orkin C et al. CROI 2019, Abstract 140.

SEATTLE – A long-acting, injectable combination of the novel integrase inhibitor cabotegravir (CAB) and the second-generation nonnucleoside reverse transcriptase inhibitor rilpivirine (RPV) was noninferior to dolutegravir/abacavir/lamivudine (DTG/ABC/3TC) in one phase 3 study (FLAIR) and to three-drug oral antiretroviral therapy (ART) more broadly in the companion ATLAS phase 3 study. Patient acceptance of the injectable formulation was surprisingly high, although researchers admitted there was likely some selection bias because patients already interested in receiving an injection would have been predisposed to entering the trials.

Ca-ssis/Thinkstock

Still, the numbers were impressive: 99% of patients who received the intramuscular injection expressed more satisfaction with it than with their previous oral regimen in the FLAIR study, and 98% expressed a similar opinion in the ATLAS study. Circumstantial evidence also suggests there may be some demand, according to Joseph Eron, MD, professor of medicine at the University of North Carolina at Chapel Hill, who commented during a press conference at the Conference on Retroviruses & Opportunistic Infections. “These studies didn’t take a long time to accrue. People were very interested, so it wasn’t as if people had to go around and beat the bushes to try to find people [to participate],” said Dr. Eron, who was not an author on either report.

“My patients tell me that they like not having to worry about taking their pills every day. There may be some relief from the stigma of HIV. You don’t have to think about it,” Susan Swindells, MBBS, medical director of the Specialty Care Clinic at the University of Nebraska Medical Center in Omaha and first author of the ATLAS trial, said during the press conference.

There were some injection site reactions, but they were generally mild and most resolved within 7 days. In the ATLAS study, 75% of participants reported injection site pain, and 1% discontinued as a result. In the FLAIR study, 82% in the CAB/RPV arm experienced an injection site reaction, with a median duration of 3 days; 99% of reactions were grade 1 or 2.

Should the combination achieve regulatory approval, it remains to be seen how challenging it will be to manage patients with monthly injections and ensure they stick to the schedule. The injections must be administered by a health care provider.

“In terms of generalizability outside of the study, it would be a paradigm shift in our therapy,” Chloe Orkin, MBBCh, said at a press conference. Dr. Orkin is the first author on the FLAIR trial report and a consultant in HIV Medicine at Barts Health National Health Service Trust. She pointed to the example of injectable contraception. “It can be done. It’s just that we haven’t done it. It will require some thought,” Dr. Orkin added.

In the ATLAS study, 616 participants taking two nucleoside reverse transcriptase inhibitor (NRTIs) and an integrase inhibitor, a non-NRTI, or a protease inhibitor, were randomized 1:1 to continue their regimen (CART arm) or switch to CAB/RPV, following a 4-week safety monitoring period of oral CAB/RPV. After 48 weeks, 1.6% in the CAB/RPV arm and 1.0% in the CART arm had HIV-1 RNA greater than or equal to 50 copies/mL, which met the prespecified noninferiority margin. Of patients in the CAB/RPV arm, 93% had HIV-1 RNA less than 50 copies/mL at week 48 versus 95% in the CART arm, and the difference was not statistically significant. Grade 3 or 4 events were seen in 11% of CAB/RPV and 7% of CART patients.

The FLAIR study randomized 566 ART-naive patients to receive either CAB/RPV or DTG/ABC/3TC after a 20-week induction phase, followed by a 4-week safety monitoring period for those going into the CAB/RPV arm. At week 48, 2.1% in the CAB/RPV arm and 2.5% in the DTG/ABC/3TC arm had HIV-1 RNA greater than or equal to 50 copies/mL, which met the prespecified noninferiority margin, while 94% in the CAB/RPV arm and 93% in the DTG/ABC/3TC arm had HIV-1 RNA less than 50 copies/mL. Confirmed virologic failure occurred in four patients (1.4%) in the CAB/RPV arm, and three of those patients had mutations in the NNRTI+INSTI domains, while the fourth patient was not tested. Three failures occurred in the DTG/ABC/3TC arm, and none of those patients had INSTI resistance mutations. A total of 82% of CAB/RPV patients had injection site reactions, 99% of which were grade 1 or 2, and the median duration was 3 days.

The ATLAS and FLAIR studies were sponsored by ViiV. Janssen and GlaxoSmithKline were collaborators.

SOURCES: Swindells S et al. CROI 2019, Abstract 139 LB. Orkin C et al. CROI 2019, Abstract 140.

SEATTLE – A long-acting, injectable combination of the novel integrase inhibitor cabotegravir (CAB) and the second-generation nonnucleoside reverse transcriptase inhibitor rilpivirine (RPV) was noninferior to dolutegravir/abacavir/lamivudine (DTG/ABC/3TC) in one phase 3 study (FLAIR) and to three-drug oral antiretroviral therapy (ART) more broadly in the companion ATLAS phase 3 study. Patient acceptance of the injectable formulation was surprisingly high, although researchers admitted there was likely some selection bias because patients already interested in receiving an injection would have been predisposed to entering the trials.

Ca-ssis/Thinkstock

Still, the numbers were impressive: 99% of patients who received the intramuscular injection expressed more satisfaction with it than with their previous oral regimen in the FLAIR study, and 98% expressed a similar opinion in the ATLAS study. Circumstantial evidence also suggests there may be some demand, according to Joseph Eron, MD, professor of medicine at the University of North Carolina at Chapel Hill, who commented during a press conference at the Conference on Retroviruses & Opportunistic Infections. “These studies didn’t take a long time to accrue. People were very interested, so it wasn’t as if people had to go around and beat the bushes to try to find people [to participate],” said Dr. Eron, who was not an author on either report.

“My patients tell me that they like not having to worry about taking their pills every day. There may be some relief from the stigma of HIV. You don’t have to think about it,” Susan Swindells, MBBS, medical director of the Specialty Care Clinic at the University of Nebraska Medical Center in Omaha and first author of the ATLAS trial, said during the press conference.

There were some injection site reactions, but they were generally mild and most resolved within 7 days. In the ATLAS study, 75% of participants reported injection site pain, and 1% discontinued as a result. In the FLAIR study, 82% in the CAB/RPV arm experienced an injection site reaction, with a median duration of 3 days; 99% of reactions were grade 1 or 2.

Should the combination achieve regulatory approval, it remains to be seen how challenging it will be to manage patients with monthly injections and ensure they stick to the schedule. The injections must be administered by a health care provider.

“In terms of generalizability outside of the study, it would be a paradigm shift in our therapy,” Chloe Orkin, MBBCh, said at a press conference. Dr. Orkin is the first author on the FLAIR trial report and a consultant in HIV Medicine at Barts Health National Health Service Trust. She pointed to the example of injectable contraception. “It can be done. It’s just that we haven’t done it. It will require some thought,” Dr. Orkin added.

In the ATLAS study, 616 participants taking two nucleoside reverse transcriptase inhibitor (NRTIs) and an integrase inhibitor, a non-NRTI, or a protease inhibitor, were randomized 1:1 to continue their regimen (CART arm) or switch to CAB/RPV, following a 4-week safety monitoring period of oral CAB/RPV. After 48 weeks, 1.6% in the CAB/RPV arm and 1.0% in the CART arm had HIV-1 RNA greater than or equal to 50 copies/mL, which met the prespecified noninferiority margin. Of patients in the CAB/RPV arm, 93% had HIV-1 RNA less than 50 copies/mL at week 48 versus 95% in the CART arm, and the difference was not statistically significant. Grade 3 or 4 events were seen in 11% of CAB/RPV and 7% of CART patients.

The FLAIR study randomized 566 ART-naive patients to receive either CAB/RPV or DTG/ABC/3TC after a 20-week induction phase, followed by a 4-week safety monitoring period for those going into the CAB/RPV arm. At week 48, 2.1% in the CAB/RPV arm and 2.5% in the DTG/ABC/3TC arm had HIV-1 RNA greater than or equal to 50 copies/mL, which met the prespecified noninferiority margin, while 94% in the CAB/RPV arm and 93% in the DTG/ABC/3TC arm had HIV-1 RNA less than 50 copies/mL. Confirmed virologic failure occurred in four patients (1.4%) in the CAB/RPV arm, and three of those patients had mutations in the NNRTI+INSTI domains, while the fourth patient was not tested. Three failures occurred in the DTG/ABC/3TC arm, and none of those patients had INSTI resistance mutations. A total of 82% of CAB/RPV patients had injection site reactions, 99% of which were grade 1 or 2, and the median duration was 3 days.

The ATLAS and FLAIR studies were sponsored by ViiV. Janssen and GlaxoSmithKline were collaborators.

SOURCES: Swindells S et al. CROI 2019, Abstract 139 LB. Orkin C et al. CROI 2019, Abstract 140.

SEATTLE – A marked increase in the risk of sudden cardiac death among people with HIV correlates with a significantly higher burden of myocardial fibrosis, according to an autopsy study presented at the Conference on Retroviruses and Opportunistic Infections.

M. Alexander Otto/MDedge News

Fibrosis is a known trigger for fatal arrhythmias, so the take home is that fibrosis should be considered as a criteria for defibrillator implantation in HIV patients, said lead investigator Zian Tseng, MD, a cardiologist, cardiac electrophysiologist, and professor of medicine at the University of California, San Francisco.

The finding also speaks to a larger issue. The main criterion right now for implantation is an ejection fraction below 35%, but “there are a lot of people who die suddenly with normal ejection fractions,” and not just people with HIV, he said.

Many of those deaths might be prevented if fibrosis is added to implantation criteria. All that’s needed for assessment is a cardiac MRI, Dr. Tseng said.

The approach would be particularly fruitful for HIV patients, but cardiac fibrosis “isn’t just an” HIV problem, he said.

The conclusions have their roots in an investigation to determine the true incidence of sudden cardiac death (SCD) in the general public. SCD is commonly listed on death certificates, but it’s a presumed diagnosis, based on the best guesses of paramedics and clinicians. Autopsy is the only way to know for sure if a death was truly due to a sudden cardiac arrhythmia, or even related to the heart,

To clear the wheat from the chaff, Dr. Tseng and his colleagues performed autopsies on 525 out-of-hospital SCD cases among adults in San Francisco from 2011-2016; to qualify, the cases had to meet World Health Organization SCD criteria, meaning unexpected death within 1 hour of symptom onset, or, in unwitnessed cases, within 24 hours of when the person was last seen alive and well.

Cases were considered sudden arrhythmic death – and, therefore, true SCD – if no extracardiac causes of death or acute heart failure were found on autopsy. Overall, 40% of deaths attributed to SCD “were not sudden or unexpected, and nearly half of presumed SCDs were not arrhythmic.” The findings had “implications for ... mortality data, clinical trials, and cohort studies,” Dr. Tseng and his team concluded (Circulation. 2018 Jun 19;137[25]:2689-2700).

They next turned their attention to HIV. It’s known that the virus increases the risk of strokes, heart attacks, and heart failure; the researchers wanted to see if it did the same for SCD. The HIV results were presented at CROI.

Forty-seven presumed SCD cases with HIV met inclusion criteria during the study period. Based on the earlier findings and epidemiological data, people with HIV had more than an 80% higher risk of SCD and an almost 60% higher risk of confirmed arrhythmic death than did the general public. Similar to the general population, only about half of presumed SCD cases were confirmed on autopsy. About one-third of what turned out to be non-cardiac HIV deaths were due to occult overdose, versus 13.5% in the general population, which points to the increased need for drug screening and treatment in HIV.

Beyond that, though, the team found that the burden of myocardial fibrosis in HIV “was profound,” far surpassing what was found in SCD deaths in the general population. After adjustment for age, gender, and heart disease, “sudden cardiac deaths with HIV had 60% higher interstitial fibrosis by myocardial trichrome staining. Cardiac fibrosis, a known substrate for fatal arrhythmias in the general population, may underlie the mechanism by which HIV increases the risk” of sudden death in HIV, Dr. Tseng said.

It could be that the virus enters heart cells and sets off an inflammatory cardiomyopathy, or perhaps it’s related to chronic inflammation caused by the virus. Whatever the case, infection seems to have an “independent effect” on increasing fibrosis among people with HIV, he said.

Intriguingly, a large epidemiologic study in United States veterans, also presented at CROI, found a higher risk of SCD among HIV patients, but only if their infections were active over an extended period of time, as indicated by sustained high viral loads and low CD4 cell counts. Dr. Tseng was involved in that work, as well, but noted that the number of HIV SCD cases in the San Francisco study was too small to draw meaningful conclusions regarding the relationship between disease control and cardiac fibrosis.

Cardiac defibrillators can prevent arrhythmic death, so, at least for now, he said that the autopsy study findings mean that criteria for implantation should be broadened to include extensive cardiac fibrosis.

The work was funded by the National Institutes of Health. Dr. Tseng didn’t have any disclosures.

[email protected]

SOURCE: Tseng ZH et al. CROI 2019 abstract 32

SEATTLE – A marked increase in the risk of sudden cardiac death among people with HIV correlates with a significantly higher burden of myocardial fibrosis, according to an autopsy study presented at the Conference on Retroviruses and Opportunistic Infections.

M. Alexander Otto/MDedge News

Fibrosis is a known trigger for fatal arrhythmias, so the take home is that fibrosis should be considered as a criteria for defibrillator implantation in HIV patients, said lead investigator Zian Tseng, MD, a cardiologist, cardiac electrophysiologist, and professor of medicine at the University of California, San Francisco.

The finding also speaks to a larger issue. The main criterion right now for implantation is an ejection fraction below 35%, but “there are a lot of people who die suddenly with normal ejection fractions,” and not just people with HIV, he said.

Many of those deaths might be prevented if fibrosis is added to implantation criteria. All that’s needed for assessment is a cardiac MRI, Dr. Tseng said.

The approach would be particularly fruitful for HIV patients, but cardiac fibrosis “isn’t just an” HIV problem, he said.

The conclusions have their roots in an investigation to determine the true incidence of sudden cardiac death (SCD) in the general public. SCD is commonly listed on death certificates, but it’s a presumed diagnosis, based on the best guesses of paramedics and clinicians. Autopsy is the only way to know for sure if a death was truly due to a sudden cardiac arrhythmia, or even related to the heart,

To clear the wheat from the chaff, Dr. Tseng and his colleagues performed autopsies on 525 out-of-hospital SCD cases among adults in San Francisco from 2011-2016; to qualify, the cases had to meet World Health Organization SCD criteria, meaning unexpected death within 1 hour of symptom onset, or, in unwitnessed cases, within 24 hours of when the person was last seen alive and well.

Cases were considered sudden arrhythmic death – and, therefore, true SCD – if no extracardiac causes of death or acute heart failure were found on autopsy. Overall, 40% of deaths attributed to SCD “were not sudden or unexpected, and nearly half of presumed SCDs were not arrhythmic.” The findings had “implications for ... mortality data, clinical trials, and cohort studies,” Dr. Tseng and his team concluded (Circulation. 2018 Jun 19;137[25]:2689-2700).

They next turned their attention to HIV. It’s known that the virus increases the risk of strokes, heart attacks, and heart failure; the researchers wanted to see if it did the same for SCD. The HIV results were presented at CROI.

Forty-seven presumed SCD cases with HIV met inclusion criteria during the study period. Based on the earlier findings and epidemiological data, people with HIV had more than an 80% higher risk of SCD and an almost 60% higher risk of confirmed arrhythmic death than did the general public. Similar to the general population, only about half of presumed SCD cases were confirmed on autopsy. About one-third of what turned out to be non-cardiac HIV deaths were due to occult overdose, versus 13.5% in the general population, which points to the increased need for drug screening and treatment in HIV.

Beyond that, though, the team found that the burden of myocardial fibrosis in HIV “was profound,” far surpassing what was found in SCD deaths in the general population. After adjustment for age, gender, and heart disease, “sudden cardiac deaths with HIV had 60% higher interstitial fibrosis by myocardial trichrome staining. Cardiac fibrosis, a known substrate for fatal arrhythmias in the general population, may underlie the mechanism by which HIV increases the risk” of sudden death in HIV, Dr. Tseng said.

It could be that the virus enters heart cells and sets off an inflammatory cardiomyopathy, or perhaps it’s related to chronic inflammation caused by the virus. Whatever the case, infection seems to have an “independent effect” on increasing fibrosis among people with HIV, he said.

Intriguingly, a large epidemiologic study in United States veterans, also presented at CROI, found a higher risk of SCD among HIV patients, but only if their infections were active over an extended period of time, as indicated by sustained high viral loads and low CD4 cell counts. Dr. Tseng was involved in that work, as well, but noted that the number of HIV SCD cases in the San Francisco study was too small to draw meaningful conclusions regarding the relationship between disease control and cardiac fibrosis.

Cardiac defibrillators can prevent arrhythmic death, so, at least for now, he said that the autopsy study findings mean that criteria for implantation should be broadened to include extensive cardiac fibrosis.

The work was funded by the National Institutes of Health. Dr. Tseng didn’t have any disclosures.

[email protected]

SOURCE: Tseng ZH et al. CROI 2019 abstract 32

SEATTLE – A marked increase in the risk of sudden cardiac death among people with HIV correlates with a significantly higher burden of myocardial fibrosis, according to an autopsy study presented at the Conference on Retroviruses and Opportunistic Infections.

M. Alexander Otto/MDedge News

Fibrosis is a known trigger for fatal arrhythmias, so the take home is that fibrosis should be considered as a criteria for defibrillator implantation in HIV patients, said lead investigator Zian Tseng, MD, a cardiologist, cardiac electrophysiologist, and professor of medicine at the University of California, San Francisco.

The finding also speaks to a larger issue. The main criterion right now for implantation is an ejection fraction below 35%, but “there are a lot of people who die suddenly with normal ejection fractions,” and not just people with HIV, he said.

Many of those deaths might be prevented if fibrosis is added to implantation criteria. All that’s needed for assessment is a cardiac MRI, Dr. Tseng said.

The approach would be particularly fruitful for HIV patients, but cardiac fibrosis “isn’t just an” HIV problem, he said.

The conclusions have their roots in an investigation to determine the true incidence of sudden cardiac death (SCD) in the general public. SCD is commonly listed on death certificates, but it’s a presumed diagnosis, based on the best guesses of paramedics and clinicians. Autopsy is the only way to know for sure if a death was truly due to a sudden cardiac arrhythmia, or even related to the heart,

To clear the wheat from the chaff, Dr. Tseng and his colleagues performed autopsies on 525 out-of-hospital SCD cases among adults in San Francisco from 2011-2016; to qualify, the cases had to meet World Health Organization SCD criteria, meaning unexpected death within 1 hour of symptom onset, or, in unwitnessed cases, within 24 hours of when the person was last seen alive and well.

Cases were considered sudden arrhythmic death – and, therefore, true SCD – if no extracardiac causes of death or acute heart failure were found on autopsy. Overall, 40% of deaths attributed to SCD “were not sudden or unexpected, and nearly half of presumed SCDs were not arrhythmic.” The findings had “implications for ... mortality data, clinical trials, and cohort studies,” Dr. Tseng and his team concluded (Circulation. 2018 Jun 19;137[25]:2689-2700).

They next turned their attention to HIV. It’s known that the virus increases the risk of strokes, heart attacks, and heart failure; the researchers wanted to see if it did the same for SCD. The HIV results were presented at CROI.

Forty-seven presumed SCD cases with HIV met inclusion criteria during the study period. Based on the earlier findings and epidemiological data, people with HIV had more than an 80% higher risk of SCD and an almost 60% higher risk of confirmed arrhythmic death than did the general public. Similar to the general population, only about half of presumed SCD cases were confirmed on autopsy. About one-third of what turned out to be non-cardiac HIV deaths were due to occult overdose, versus 13.5% in the general population, which points to the increased need for drug screening and treatment in HIV.

Beyond that, though, the team found that the burden of myocardial fibrosis in HIV “was profound,” far surpassing what was found in SCD deaths in the general population. After adjustment for age, gender, and heart disease, “sudden cardiac deaths with HIV had 60% higher interstitial fibrosis by myocardial trichrome staining. Cardiac fibrosis, a known substrate for fatal arrhythmias in the general population, may underlie the mechanism by which HIV increases the risk” of sudden death in HIV, Dr. Tseng said.

It could be that the virus enters heart cells and sets off an inflammatory cardiomyopathy, or perhaps it’s related to chronic inflammation caused by the virus. Whatever the case, infection seems to have an “independent effect” on increasing fibrosis among people with HIV, he said.

Intriguingly, a large epidemiologic study in United States veterans, also presented at CROI, found a higher risk of SCD among HIV patients, but only if their infections were active over an extended period of time, as indicated by sustained high viral loads and low CD4 cell counts. Dr. Tseng was involved in that work, as well, but noted that the number of HIV SCD cases in the San Francisco study was too small to draw meaningful conclusions regarding the relationship between disease control and cardiac fibrosis.

Cardiac defibrillators can prevent arrhythmic death, so, at least for now, he said that the autopsy study findings mean that criteria for implantation should be broadened to include extensive cardiac fibrosis.

The work was funded by the National Institutes of Health. Dr. Tseng didn’t have any disclosures.

[email protected]

SOURCE: Tseng ZH et al. CROI 2019 abstract 32

The decline of influenza activity remains slow, largely “driven by a wave of H3N2 virus activity” in recent weeks, according to the Centers for Disease Control and Prevention.

Fewer states reported the highest level of influenza-like illness (ILI) activity on the CDC’s 1-10 scale for the week ending March 16, but the national proportion of outpatient visits for ILI was 4.4% for the second consecutive week, the CDC’s influenza division reported March 22. The outpatient-visit figure for the week ending March 9 was originally reported as 4.5% last week, but it has been revised down to 4.4% this week.

Another measure of activity – the percentage of respiratory specimens testing positive for influenza viruses in clinical laboratories – actually increased slightly during the week ending March 16, the CDC noted.

For the current week, there were 26 states in the high (8-10) range of activity – 20 states were at level 10 and another 6 states were at level 8 – compared with the previous week, when 21 states were at level 10 and 30 states were in the high range, the CDC’s Outpatient ILI Surveillance Network reported.

There were eight ILI-related deaths in children reported during the week ending March 16, seven of which occurred in previous weeks. The total for the 2018-2019 season so far is 76, the CDC said.

New preliminary estimates on influenza’s burden nationally put the total number of deaths at 25,000-41,500 since the beginning of the season on Oct. 1, 2018. There also have been 375,000-454,000 flu-related hospitalizations, 13.2 million to 15.4 million medical visits, and 28.5 to 32.8 million individual illnesses, the CDC said.

Since the CDC “expects flu activity to remain elevated for a number of weeks,” it continues to recommend flu vaccination and the use of influenza antiviral drugs as “an important second line of defense that can be used to treat flu illness. H3N2 viruses are typically associated with more severe illness in older adults, and flu vaccine may protect less well against H3N2 illness in older adults, making prompt treatment with flu antivirals in this age group especially important during the current period of H3N2 predominance.”

[email protected]

The decline of influenza activity remains slow, largely “driven by a wave of H3N2 virus activity” in recent weeks, according to the Centers for Disease Control and Prevention.

Fewer states reported the highest level of influenza-like illness (ILI) activity on the CDC’s 1-10 scale for the week ending March 16, but the national proportion of outpatient visits for ILI was 4.4% for the second consecutive week, the CDC’s influenza division reported March 22. The outpatient-visit figure for the week ending March 9 was originally reported as 4.5% last week, but it has been revised down to 4.4% this week.

Another measure of activity – the percentage of respiratory specimens testing positive for influenza viruses in clinical laboratories – actually increased slightly during the week ending March 16, the CDC noted.

For the current week, there were 26 states in the high (8-10) range of activity – 20 states were at level 10 and another 6 states were at level 8 – compared with the previous week, when 21 states were at level 10 and 30 states were in the high range, the CDC’s Outpatient ILI Surveillance Network reported.

There were eight ILI-related deaths in children reported during the week ending March 16, seven of which occurred in previous weeks. The total for the 2018-2019 season so far is 76, the CDC said.

New preliminary estimates on influenza’s burden nationally put the total number of deaths at 25,000-41,500 since the beginning of the season on Oct. 1, 2018. There also have been 375,000-454,000 flu-related hospitalizations, 13.2 million to 15.4 million medical visits, and 28.5 to 32.8 million individual illnesses, the CDC said.

Since the CDC “expects flu activity to remain elevated for a number of weeks,” it continues to recommend flu vaccination and the use of influenza antiviral drugs as “an important second line of defense that can be used to treat flu illness. H3N2 viruses are typically associated with more severe illness in older adults, and flu vaccine may protect less well against H3N2 illness in older adults, making prompt treatment with flu antivirals in this age group especially important during the current period of H3N2 predominance.”

[email protected]

The decline of influenza activity remains slow, largely “driven by a wave of H3N2 virus activity” in recent weeks, according to the Centers for Disease Control and Prevention.

Fewer states reported the highest level of influenza-like illness (ILI) activity on the CDC’s 1-10 scale for the week ending March 16, but the national proportion of outpatient visits for ILI was 4.4% for the second consecutive week, the CDC’s influenza division reported March 22. The outpatient-visit figure for the week ending March 9 was originally reported as 4.5% last week, but it has been revised down to 4.4% this week.

Another measure of activity – the percentage of respiratory specimens testing positive for influenza viruses in clinical laboratories – actually increased slightly during the week ending March 16, the CDC noted.

For the current week, there were 26 states in the high (8-10) range of activity – 20 states were at level 10 and another 6 states were at level 8 – compared with the previous week, when 21 states were at level 10 and 30 states were in the high range, the CDC’s Outpatient ILI Surveillance Network reported.

There were eight ILI-related deaths in children reported during the week ending March 16, seven of which occurred in previous weeks. The total for the 2018-2019 season so far is 76, the CDC said.

New preliminary estimates on influenza’s burden nationally put the total number of deaths at 25,000-41,500 since the beginning of the season on Oct. 1, 2018. There also have been 375,000-454,000 flu-related hospitalizations, 13.2 million to 15.4 million medical visits, and 28.5 to 32.8 million individual illnesses, the CDC said.

Since the CDC “expects flu activity to remain elevated for a number of weeks,” it continues to recommend flu vaccination and the use of influenza antiviral drugs as “an important second line of defense that can be used to treat flu illness. H3N2 viruses are typically associated with more severe illness in older adults, and flu vaccine may protect less well against H3N2 illness in older adults, making prompt treatment with flu antivirals in this age group especially important during the current period of H3N2 predominance.”

[email protected]

WAIKOLOA, HAWAII – It’s easy to misdiagnose scabies in infants because it doesn’t present with the usual signs and symptoms in this age group.

“It’s really important to think of scabies in any widespread rash that a baby presents with,” said Andrea Zaenglein, MD, professor of dermatology and pediatric dermatology at Penn State University, Hershey. It’s often missed in the ED because it’s not recognized.

While lesions might be limited to the webbing of the hands in older patients, infants generally have a widespread rash with many different lesion types involving the armpits, trunk, and even the scalp. “In older kids, we always think of itch as our primary criteria, but for infants with scabies, that’s not always the case. The younger the kid, the less able they’re to manifest the itch in a way that we recognize,” she said in an interview at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.

Standard treatment for infants with scabies is permethrin cream, which, Dr. Zaenglein advises, should be applied from head to toe. “And make sure to treat all family members, even if they’re not demonstrating any symptoms. It’s really important, because that baby had to get scabies from somebody,” she said. Although permethrin isn’t approved for use under 2 months old, she said she has no problem with it in younger, otherwise healthy infants, but cases below 2 months are uncommon. Even if infants are exposed at birth, it takes several weeks for scabies to manifest.

Topical corticosteroids are useful as well to speed healing and help with itch. Ivermectin is held in reserve for older patients, especially in institutional settings where many people have to be treated at a time, or when permethrin cream is not effective.

SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

[email protected]

WAIKOLOA, HAWAII – It’s easy to misdiagnose scabies in infants because it doesn’t present with the usual signs and symptoms in this age group.

“It’s really important to think of scabies in any widespread rash that a baby presents with,” said Andrea Zaenglein, MD, professor of dermatology and pediatric dermatology at Penn State University, Hershey. It’s often missed in the ED because it’s not recognized.

While lesions might be limited to the webbing of the hands in older patients, infants generally have a widespread rash with many different lesion types involving the armpits, trunk, and even the scalp. “In older kids, we always think of itch as our primary criteria, but for infants with scabies, that’s not always the case. The younger the kid, the less able they’re to manifest the itch in a way that we recognize,” she said in an interview at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.

Standard treatment for infants with scabies is permethrin cream, which, Dr. Zaenglein advises, should be applied from head to toe. “And make sure to treat all family members, even if they’re not demonstrating any symptoms. It’s really important, because that baby had to get scabies from somebody,” she said. Although permethrin isn’t approved for use under 2 months old, she said she has no problem with it in younger, otherwise healthy infants, but cases below 2 months are uncommon. Even if infants are exposed at birth, it takes several weeks for scabies to manifest.

Topical corticosteroids are useful as well to speed healing and help with itch. Ivermectin is held in reserve for older patients, especially in institutional settings where many people have to be treated at a time, or when permethrin cream is not effective.

SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

[email protected]

WAIKOLOA, HAWAII – It’s easy to misdiagnose scabies in infants because it doesn’t present with the usual signs and symptoms in this age group.

“It’s really important to think of scabies in any widespread rash that a baby presents with,” said Andrea Zaenglein, MD, professor of dermatology and pediatric dermatology at Penn State University, Hershey. It’s often missed in the ED because it’s not recognized.

While lesions might be limited to the webbing of the hands in older patients, infants generally have a widespread rash with many different lesion types involving the armpits, trunk, and even the scalp. “In older kids, we always think of itch as our primary criteria, but for infants with scabies, that’s not always the case. The younger the kid, the less able they’re to manifest the itch in a way that we recognize,” she said in an interview at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.

Standard treatment for infants with scabies is permethrin cream, which, Dr. Zaenglein advises, should be applied from head to toe. “And make sure to treat all family members, even if they’re not demonstrating any symptoms. It’s really important, because that baby had to get scabies from somebody,” she said. Although permethrin isn’t approved for use under 2 months old, she said she has no problem with it in younger, otherwise healthy infants, but cases below 2 months are uncommon. Even if infants are exposed at birth, it takes several weeks for scabies to manifest.

Topical corticosteroids are useful as well to speed healing and help with itch. Ivermectin is held in reserve for older patients, especially in institutional settings where many people have to be treated at a time, or when permethrin cream is not effective.

SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

[email protected]

The Food and Drug Administration is planning a pilot study of a new HIV risk questionnaire, as part of a comprehensive and ongoing evaluation of its blood donation policies for men who have sex with men (MSM).

At a meeting of the FDA’s Blood Products Advisory Committee, the agency shared the content of the 5-item questionnaire and reviewed the proposed study design with committee members, who were asked to comment – but not vote – on the best path forward for MSM donation policies.

The FDA is “committed to ongoing evaluation of the MSM deferral policy” and remains open to adjusting the policy based on the best available scientific evidence, said Barbee Whitaker, PhD, a lead scientist in the agency’s Office of Emerging and Transfusion Transmitted Disease

After recruiting 2,000 men who have had sex with men at least once during the past 3 months, the study will aim to identify individuals who have very recently become HIV infected, in order to assess the discriminant function of the set of behavioral questions that are proposed in the questionnaire.

The crux of the problem currently, noted Dr. Whitaker, is identifying those individuals who are very recently infected with HIV. Nucleic acid testing has tightened the window of undetectability considerably, but the current 12-month deferral window after men have had sexual contact with other men is designed to ensure safety of the blood supply.

Social justice concerns have been raised about the blanket deferral, said Dr. Whitaker; the behavioral questions in the pilot study will ask about the number of different sexual partners men have had within the past 1, 3, and 12 months and ask about the type of sexual contact (oral sex, or anal penetrative or receptive intercourse). The questionnaire also asks about sex with a partner known to be HIV positive, condom use, and use of pre-exposure prophylaxis (PrEP).

The FDA will ask for proposals to conduct the study with an eye to having sites in such cities as Washington, Atlanta, and Miami, which have high incidences of HIV, to improve chances of early detection.

The behavioral questionnaire is not seen as an immediate replacement for the 12-month deferral policy, the FDA made clear in its briefing documents and in discussion with the committee. Instead, its utility will be in the information gleaned from the pilot study and a follow-on that may include several hundred thousand individuals. These data should provide “population-based evidence upon which to base regulatory decisions to ensure blood safety,” she said.

Donation policies outside the United States

Whether a change in blood donation deferral policies for MSM would be a shortened window or a move toward a behavioral questionnaire is currently not known. Globally, a variety of practices are used for blood screening, said Mindy Goldman, MD, medical director of Canadian Blood Services, who reviewed international perspectives on blood donation for MSM.

“There’s no general consensus on donation deferrals internationally,” she said. Factors influencing policy can include epidemiology, risk analysis, modeling, and history of response to threats in the past.

However, “there’s basically a couple of main approaches” to handling deferrals for MSM, Dr. Goldman said. One is time-based deferral – the strategy used in the United States, as well as Canada, the United Kingdom, Japan, and Australia.

Japan and the U.K. have recently moved to 3-month deferral periods, a figure arrived at by doubling the window period for nucleic acid testing for HIV, roughly, Dr. Goldman said. Early data from the U.K. experience has not shown an increase in HIV rates among donors, or an increase in NAT-only positive donors, she said. An application to move from a 12-month to a 3-month deferral period is pending in Canada.

A strong advantage of time-based deferral as a risk management strategy, Dr. Goldman said, is standardization. “For us, standardization is close to godliness.”

However, she added, “another major limitation is that you’re still deferring all sexually active MSM, including those who are in a stable monogamous relationship from donating. From a justice perspective for the lowest risk population of MSM – they are still being deferred using this type of approach.”

Some nations, such as Spain and Italy, use individual risk assessment via physician-led interviews. These approaches are often not standardized. “There’s no national uniform questionnaire, so there’s less standardization, and more variability between blood centers,” Dr. Goldman said. “So you wind up trying to compare apples with oranges.”

This means the results are harder to evaluate on a national level. However, there appears to be higher residual risk, with HIV rates among first-time donors approaching those of the general population, Dr. Goldman said.

Another strategy, used in France, is a test-retest model, where blood from first-time MSM that initially tests negative for HIV is held until the individual returns for re-testing or an additional donation, with a second negative test. This approach increases operational complexity and cost, noted Dr. Goldman, and because of the short shelf life of platelets, it’s not practical for this blood component.

In general questioning and discussion after this and other background presentations, the committee could agree on one point: this isn’t an easy question.

“I’m increasingly struck by how difficult this problem is,” said committee member Roger Lewis, MD, PhD, professor at the University of California, Los Angeles, and chair of the department of emergency medicine at Harbor-UCLA Medical Center. Regarding just the problem of completing the pilot study, Dr. Lewis commented, “It sounds like it’s going to be impossible to get the data that directly answers the questions.”

Peter Marx, MD, PhD, who directs the FDA’s Center for Biologics Evaluation and Research (CBER), which oversees blood products safety, joined the discussion to acknowledge the difficulty, but underscore the social importance of a careful examination of the current MSM donation policy.

“We understand the issues here…. With all due respect to our European colleagues, there’s not enough data. That’s the point of this study; we also know that the U.S. has a very different epidemiology of HIV than the U.K. and a lot of other places,” Dr. Marx said. “The pilot study is a way to get some data where we might be able to get away from a time-based deferral. The LGBT community finds any time-based deferral discriminatory.”

Pathogen reduction technology

The committee heard a proposal for a completely different strategy during its afternoon session: pathogen reduction technology (PRT) holds promise to achieve virtual elimination of HIV and other pathogens from donated blood products.

The FDA is reviewing a variance request from the nonprofit blood donation organization Bloodworks Northwest organization to use PRT for apheresis platelet donations from MSM who would otherwise be deferred because of sexual activity within the 12-month deferral window.

James AuBuchon, MD, president of Bloodworks Northwest, explained that his organization takes in about 225,000 donations annually. The variance sought would use the FDA-approved INTERCEPT device to achieve pathogen reduction for donations that meet all requirements except the MSM deferral, and that would still undergo all relevant transfusion transmitted infection testing.

The INTERCEPT device uses amotosalen, which intercalates with DNA and RNA, inactivating it after exposure to ultraviolet A light. Amotosalen is then removed from the blood product before administration. The pathogen reduction activity doesn’t interfere with platelets or plasma, and is active against a wide range of viruses, bacteria, and fungal pathogens, explained Dr. AuBuchon, who is also a professor of hematology at the University of Washington, Seattle.

Dr. AuBuchon walked the committee through procedures designed to flag donors for PRT platelet apheresis, and to ensure these donations receive the intended PRT treatment. Platelets were chosen for this variance request, he explained, because demand outstrips supply. “We are all spending additional time and resources in recruiting a new framework and demographic, and it is exceedingly difficult to keep enough donors coming through the door,” he said. “Our platelet utilization climbs continually – it’s up 15% in the last 4 years.”

Committee members circled around the idea that all risk can’t be eliminated, even with the highly effective PRT technology. But the risk is exceedingly low, said committee chair Richard Kaufman, MD, medical director of the adult transfusion service at Brigham and Women’s Hospital, Boston. “It’s not possible to get rid of the window. We can kind of hammer down the risk by shrinking down the window by using incredibly sensitive tests. But that risk continues to exist. Pathogen reduction can take care of that residual risk…. So what’s left is really quite a low risk,” Dr. Kaufman said.

Susan Stramer, PhD, vice president of scientific affairs for the American Red Cross, concurred, noting that pathogen reduction techniques are already in use for many other blood products, particularly within the plasma industry.

Wrapping up, Dr. Kaufman asked individual committee members to summarize their position on the variance request, though the FDA had not placed a voting question before the committee. Consensus in the room was that this real-world examination of PRT could point to a path to expanding the donor pool while maintaining patient safety – a concern all agreed was paramount.

The FDA usually follows the recommendations of its committees.

[email protected]

The Food and Drug Administration is planning a pilot study of a new HIV risk questionnaire, as part of a comprehensive and ongoing evaluation of its blood donation policies for men who have sex with men (MSM).

At a meeting of the FDA’s Blood Products Advisory Committee, the agency shared the content of the 5-item questionnaire and reviewed the proposed study design with committee members, who were asked to comment – but not vote – on the best path forward for MSM donation policies.

The FDA is “committed to ongoing evaluation of the MSM deferral policy” and remains open to adjusting the policy based on the best available scientific evidence, said Barbee Whitaker, PhD, a lead scientist in the agency’s Office of Emerging and Transfusion Transmitted Disease

After recruiting 2,000 men who have had sex with men at least once during the past 3 months, the study will aim to identify individuals who have very recently become HIV infected, in order to assess the discriminant function of the set of behavioral questions that are proposed in the questionnaire.

The crux of the problem currently, noted Dr. Whitaker, is identifying those individuals who are very recently infected with HIV. Nucleic acid testing has tightened the window of undetectability considerably, but the current 12-month deferral window after men have had sexual contact with other men is designed to ensure safety of the blood supply.

Social justice concerns have been raised about the blanket deferral, said Dr. Whitaker; the behavioral questions in the pilot study will ask about the number of different sexual partners men have had within the past 1, 3, and 12 months and ask about the type of sexual contact (oral sex, or anal penetrative or receptive intercourse). The questionnaire also asks about sex with a partner known to be HIV positive, condom use, and use of pre-exposure prophylaxis (PrEP).

The FDA will ask for proposals to conduct the study with an eye to having sites in such cities as Washington, Atlanta, and Miami, which have high incidences of HIV, to improve chances of early detection.

The behavioral questionnaire is not seen as an immediate replacement for the 12-month deferral policy, the FDA made clear in its briefing documents and in discussion with the committee. Instead, its utility will be in the information gleaned from the pilot study and a follow-on that may include several hundred thousand individuals. These data should provide “population-based evidence upon which to base regulatory decisions to ensure blood safety,” she said.

Donation policies outside the United States

Whether a change in blood donation deferral policies for MSM would be a shortened window or a move toward a behavioral questionnaire is currently not known. Globally, a variety of practices are used for blood screening, said Mindy Goldman, MD, medical director of Canadian Blood Services, who reviewed international perspectives on blood donation for MSM.

“There’s no general consensus on donation deferrals internationally,” she said. Factors influencing policy can include epidemiology, risk analysis, modeling, and history of response to threats in the past.

However, “there’s basically a couple of main approaches” to handling deferrals for MSM, Dr. Goldman said. One is time-based deferral – the strategy used in the United States, as well as Canada, the United Kingdom, Japan, and Australia.

Japan and the U.K. have recently moved to 3-month deferral periods, a figure arrived at by doubling the window period for nucleic acid testing for HIV, roughly, Dr. Goldman said. Early data from the U.K. experience has not shown an increase in HIV rates among donors, or an increase in NAT-only positive donors, she said. An application to move from a 12-month to a 3-month deferral period is pending in Canada.

A strong advantage of time-based deferral as a risk management strategy, Dr. Goldman said, is standardization. “For us, standardization is close to godliness.”

However, she added, “another major limitation is that you’re still deferring all sexually active MSM, including those who are in a stable monogamous relationship from donating. From a justice perspective for the lowest risk population of MSM – they are still being deferred using this type of approach.”

Some nations, such as Spain and Italy, use individual risk assessment via physician-led interviews. These approaches are often not standardized. “There’s no national uniform questionnaire, so there’s less standardization, and more variability between blood centers,” Dr. Goldman said. “So you wind up trying to compare apples with oranges.”

This means the results are harder to evaluate on a national level. However, there appears to be higher residual risk, with HIV rates among first-time donors approaching those of the general population, Dr. Goldman said.

Another strategy, used in France, is a test-retest model, where blood from first-time MSM that initially tests negative for HIV is held until the individual returns for re-testing or an additional donation, with a second negative test. This approach increases operational complexity and cost, noted Dr. Goldman, and because of the short shelf life of platelets, it’s not practical for this blood component.

In general questioning and discussion after this and other background presentations, the committee could agree on one point: this isn’t an easy question.

“I’m increasingly struck by how difficult this problem is,” said committee member Roger Lewis, MD, PhD, professor at the University of California, Los Angeles, and chair of the department of emergency medicine at Harbor-UCLA Medical Center. Regarding just the problem of completing the pilot study, Dr. Lewis commented, “It sounds like it’s going to be impossible to get the data that directly answers the questions.”

Peter Marx, MD, PhD, who directs the FDA’s Center for Biologics Evaluation and Research (CBER), which oversees blood products safety, joined the discussion to acknowledge the difficulty, but underscore the social importance of a careful examination of the current MSM donation policy.

“We understand the issues here…. With all due respect to our European colleagues, there’s not enough data. That’s the point of this study; we also know that the U.S. has a very different epidemiology of HIV than the U.K. and a lot of other places,” Dr. Marx said. “The pilot study is a way to get some data where we might be able to get away from a time-based deferral. The LGBT community finds any time-based deferral discriminatory.”

Pathogen reduction technology

The committee heard a proposal for a completely different strategy during its afternoon session: pathogen reduction technology (PRT) holds promise to achieve virtual elimination of HIV and other pathogens from donated blood products.

The FDA is reviewing a variance request from the nonprofit blood donation organization Bloodworks Northwest organization to use PRT for apheresis platelet donations from MSM who would otherwise be deferred because of sexual activity within the 12-month deferral window.

James AuBuchon, MD, president of Bloodworks Northwest, explained that his organization takes in about 225,000 donations annually. The variance sought would use the FDA-approved INTERCEPT device to achieve pathogen reduction for donations that meet all requirements except the MSM deferral, and that would still undergo all relevant transfusion transmitted infection testing.

The INTERCEPT device uses amotosalen, which intercalates with DNA and RNA, inactivating it after exposure to ultraviolet A light. Amotosalen is then removed from the blood product before administration. The pathogen reduction activity doesn’t interfere with platelets or plasma, and is active against a wide range of viruses, bacteria, and fungal pathogens, explained Dr. AuBuchon, who is also a professor of hematology at the University of Washington, Seattle.

Dr. AuBuchon walked the committee through procedures designed to flag donors for PRT platelet apheresis, and to ensure these donations receive the intended PRT treatment. Platelets were chosen for this variance request, he explained, because demand outstrips supply. “We are all spending additional time and resources in recruiting a new framework and demographic, and it is exceedingly difficult to keep enough donors coming through the door,” he said. “Our platelet utilization climbs continually – it’s up 15% in the last 4 years.”

Committee members circled around the idea that all risk can’t be eliminated, even with the highly effective PRT technology. But the risk is exceedingly low, said committee chair Richard Kaufman, MD, medical director of the adult transfusion service at Brigham and Women’s Hospital, Boston. “It’s not possible to get rid of the window. We can kind of hammer down the risk by shrinking down the window by using incredibly sensitive tests. But that risk continues to exist. Pathogen reduction can take care of that residual risk…. So what’s left is really quite a low risk,” Dr. Kaufman said.

Susan Stramer, PhD, vice president of scientific affairs for the American Red Cross, concurred, noting that pathogen reduction techniques are already in use for many other blood products, particularly within the plasma industry.

Wrapping up, Dr. Kaufman asked individual committee members to summarize their position on the variance request, though the FDA had not placed a voting question before the committee. Consensus in the room was that this real-world examination of PRT could point to a path to expanding the donor pool while maintaining patient safety – a concern all agreed was paramount.

The FDA usually follows the recommendations of its committees.

[email protected]

The Food and Drug Administration is planning a pilot study of a new HIV risk questionnaire, as part of a comprehensive and ongoing evaluation of its blood donation policies for men who have sex with men (MSM).

At a meeting of the FDA’s Blood Products Advisory Committee, the agency shared the content of the 5-item questionnaire and reviewed the proposed study design with committee members, who were asked to comment – but not vote – on the best path forward for MSM donation policies.

The FDA is “committed to ongoing evaluation of the MSM deferral policy” and remains open to adjusting the policy based on the best available scientific evidence, said Barbee Whitaker, PhD, a lead scientist in the agency’s Office of Emerging and Transfusion Transmitted Disease

After recruiting 2,000 men who have had sex with men at least once during the past 3 months, the study will aim to identify individuals who have very recently become HIV infected, in order to assess the discriminant function of the set of behavioral questions that are proposed in the questionnaire.

The crux of the problem currently, noted Dr. Whitaker, is identifying those individuals who are very recently infected with HIV. Nucleic acid testing has tightened the window of undetectability considerably, but the current 12-month deferral window after men have had sexual contact with other men is designed to ensure safety of the blood supply.

Social justice concerns have been raised about the blanket deferral, said Dr. Whitaker; the behavioral questions in the pilot study will ask about the number of different sexual partners men have had within the past 1, 3, and 12 months and ask about the type of sexual contact (oral sex, or anal penetrative or receptive intercourse). The questionnaire also asks about sex with a partner known to be HIV positive, condom use, and use of pre-exposure prophylaxis (PrEP).

The FDA will ask for proposals to conduct the study with an eye to having sites in such cities as Washington, Atlanta, and Miami, which have high incidences of HIV, to improve chances of early detection.

The behavioral questionnaire is not seen as an immediate replacement for the 12-month deferral policy, the FDA made clear in its briefing documents and in discussion with the committee. Instead, its utility will be in the information gleaned from the pilot study and a follow-on that may include several hundred thousand individuals. These data should provide “population-based evidence upon which to base regulatory decisions to ensure blood safety,” she said.

Donation policies outside the United States

Whether a change in blood donation deferral policies for MSM would be a shortened window or a move toward a behavioral questionnaire is currently not known. Globally, a variety of practices are used for blood screening, said Mindy Goldman, MD, medical director of Canadian Blood Services, who reviewed international perspectives on blood donation for MSM.

“There’s no general consensus on donation deferrals internationally,” she said. Factors influencing policy can include epidemiology, risk analysis, modeling, and history of response to threats in the past.

However, “there’s basically a couple of main approaches” to handling deferrals for MSM, Dr. Goldman said. One is time-based deferral – the strategy used in the United States, as well as Canada, the United Kingdom, Japan, and Australia.

Japan and the U.K. have recently moved to 3-month deferral periods, a figure arrived at by doubling the window period for nucleic acid testing for HIV, roughly, Dr. Goldman said. Early data from the U.K. experience has not shown an increase in HIV rates among donors, or an increase in NAT-only positive donors, she said. An application to move from a 12-month to a 3-month deferral period is pending in Canada.

A strong advantage of time-based deferral as a risk management strategy, Dr. Goldman said, is standardization. “For us, standardization is close to godliness.”

However, she added, “another major limitation is that you’re still deferring all sexually active MSM, including those who are in a stable monogamous relationship from donating. From a justice perspective for the lowest risk population of MSM – they are still being deferred using this type of approach.”

Some nations, such as Spain and Italy, use individual risk assessment via physician-led interviews. These approaches are often not standardized. “There’s no national uniform questionnaire, so there’s less standardization, and more variability between blood centers,” Dr. Goldman said. “So you wind up trying to compare apples with oranges.”

This means the results are harder to evaluate on a national level. However, there appears to be higher residual risk, with HIV rates among first-time donors approaching those of the general population, Dr. Goldman said.

Another strategy, used in France, is a test-retest model, where blood from first-time MSM that initially tests negative for HIV is held until the individual returns for re-testing or an additional donation, with a second negative test. This approach increases operational complexity and cost, noted Dr. Goldman, and because of the short shelf life of platelets, it’s not practical for this blood component.

In general questioning and discussion after this and other background presentations, the committee could agree on one point: this isn’t an easy question.

“I’m increasingly struck by how difficult this problem is,” said committee member Roger Lewis, MD, PhD, professor at the University of California, Los Angeles, and chair of the department of emergency medicine at Harbor-UCLA Medical Center. Regarding just the problem of completing the pilot study, Dr. Lewis commented, “It sounds like it’s going to be impossible to get the data that directly answers the questions.”

Peter Marx, MD, PhD, who directs the FDA’s Center for Biologics Evaluation and Research (CBER), which oversees blood products safety, joined the discussion to acknowledge the difficulty, but underscore the social importance of a careful examination of the current MSM donation policy.

“We understand the issues here…. With all due respect to our European colleagues, there’s not enough data. That’s the point of this study; we also know that the U.S. has a very different epidemiology of HIV than the U.K. and a lot of other places,” Dr. Marx said. “The pilot study is a way to get some data where we might be able to get away from a time-based deferral. The LGBT community finds any time-based deferral discriminatory.”

Pathogen reduction technology

The committee heard a proposal for a completely different strategy during its afternoon session: pathogen reduction technology (PRT) holds promise to achieve virtual elimination of HIV and other pathogens from donated blood products.

The FDA is reviewing a variance request from the nonprofit blood donation organization Bloodworks Northwest organization to use PRT for apheresis platelet donations from MSM who would otherwise be deferred because of sexual activity within the 12-month deferral window.

James AuBuchon, MD, president of Bloodworks Northwest, explained that his organization takes in about 225,000 donations annually. The variance sought would use the FDA-approved INTERCEPT device to achieve pathogen reduction for donations that meet all requirements except the MSM deferral, and that would still undergo all relevant transfusion transmitted infection testing.

The INTERCEPT device uses amotosalen, which intercalates with DNA and RNA, inactivating it after exposure to ultraviolet A light. Amotosalen is then removed from the blood product before administration. The pathogen reduction activity doesn’t interfere with platelets or plasma, and is active against a wide range of viruses, bacteria, and fungal pathogens, explained Dr. AuBuchon, who is also a professor of hematology at the University of Washington, Seattle.

Dr. AuBuchon walked the committee through procedures designed to flag donors for PRT platelet apheresis, and to ensure these donations receive the intended PRT treatment. Platelets were chosen for this variance request, he explained, because demand outstrips supply. “We are all spending additional time and resources in recruiting a new framework and demographic, and it is exceedingly difficult to keep enough donors coming through the door,” he said. “Our platelet utilization climbs continually – it’s up 15% in the last 4 years.”

Committee members circled around the idea that all risk can’t be eliminated, even with the highly effective PRT technology. But the risk is exceedingly low, said committee chair Richard Kaufman, MD, medical director of the adult transfusion service at Brigham and Women’s Hospital, Boston. “It’s not possible to get rid of the window. We can kind of hammer down the risk by shrinking down the window by using incredibly sensitive tests. But that risk continues to exist. Pathogen reduction can take care of that residual risk…. So what’s left is really quite a low risk,” Dr. Kaufman said.

Susan Stramer, PhD, vice president of scientific affairs for the American Red Cross, concurred, noting that pathogen reduction techniques are already in use for many other blood products, particularly within the plasma industry.

Wrapping up, Dr. Kaufman asked individual committee members to summarize their position on the variance request, though the FDA had not placed a voting question before the committee. Consensus in the room was that this real-world examination of PRT could point to a path to expanding the donor pool while maintaining patient safety – a concern all agreed was paramount.

The FDA usually follows the recommendations of its committees.

[email protected]