HIV

Men with HIV are likely prone to the same cardiovascular risks from testosterone therapy as other men, according to new research.

There’s no reason to think they weren’t, but it hadn’t been demonstrated until now, and men with HIV are already at increased risk for cardiovascular disease. The take-home message is that “it would be prudent for clinicians to monitor closely for cardiovascular risk factors and recommend intervention to lower cardiovascular risk among men with HIV on or considering testosterone therapy,” lead investigator Sabina Haberlen, PhD, an assistant scientist in the infectious disease epidemiology division of Johns Hopkins University, Baltimore, said in a poster that was presented as part of the Conference on Retroviruses & Opportunistic Infections, which was presented online this year. CROI organizers chose to hold a virtual meeting because concerns about the spread of COVID-19.

Testosterone therapy is common among middle-aged and older men with HIV to counter the hypogonadism associated with infection. The investigators turned to the Multicenter AIDS Cohort Study – a 30-year, four-city study of HIV-1 infection in men who have sex with men – to gauge its effect.

The 300 men in the study had a baseline coronary CT angiogram in 2010-2013 and a repeat study a mean of 4.5 years later. They had no history of coronary interventions or kidney dysfunction at baseline and were aged 40-70 years, with a median age of 51 years. About 70% reported never using testosterone, 8% were former users before entering the study, 7% started using testosterone between the two CTs, and 15% entered the study on testosterone and stayed on it.

Adjusting for age, race, cardiovascular risk factors, baseline serum testosterone levels, and other potential confounders, the risk of significant coronary artery calcium (CAC) progression was 2 times greater among continuous users (P = .03) and 2.4 times greater among new users (P = .01), compared with former users, who the investigators used as a control group because, at some point, they too had indications for testosterone replacement and so were more medically similar than never users.

The risk of noncalcified plaque volume progression was also more than twice as high among ongoing users, and elevated, although not significantly so, among ongoing users.

In short, “our findings are similar to those on subclinical atherosclerotic progression” in trials of older men in the general population on testosterone replacement, Dr. Haberlen said.

About half the subjects were white, 41% were at high risk for cardiovascular disease, 91% were on antiretroviral therapy, and 81% had undetectable HIV viral loads. Median total testosterone was 606 ng/dL. CAC progression was defined by incident CAC, at least a 10 Agatston unit/year increase if the baseline CAC score was 1-100, and a 10% or more annual increase if the baseline score was above 100.

Lower baseline serum testosterone was also associated with an increased risk of CAC progression, although not progression of noncalcified plaques.

The work was funded by the National Institutes of Health. Dr. Haberlen didn’t report any relevant disclosures.

[email protected]

SOURCE: Haberlen S et al. CROI 2020, Abstract 662.

Men with HIV are likely prone to the same cardiovascular risks from testosterone therapy as other men, according to new research.

There’s no reason to think they weren’t, but it hadn’t been demonstrated until now, and men with HIV are already at increased risk for cardiovascular disease. The take-home message is that “it would be prudent for clinicians to monitor closely for cardiovascular risk factors and recommend intervention to lower cardiovascular risk among men with HIV on or considering testosterone therapy,” lead investigator Sabina Haberlen, PhD, an assistant scientist in the infectious disease epidemiology division of Johns Hopkins University, Baltimore, said in a poster that was presented as part of the Conference on Retroviruses & Opportunistic Infections, which was presented online this year. CROI organizers chose to hold a virtual meeting because concerns about the spread of COVID-19.

Testosterone therapy is common among middle-aged and older men with HIV to counter the hypogonadism associated with infection. The investigators turned to the Multicenter AIDS Cohort Study – a 30-year, four-city study of HIV-1 infection in men who have sex with men – to gauge its effect.

The 300 men in the study had a baseline coronary CT angiogram in 2010-2013 and a repeat study a mean of 4.5 years later. They had no history of coronary interventions or kidney dysfunction at baseline and were aged 40-70 years, with a median age of 51 years. About 70% reported never using testosterone, 8% were former users before entering the study, 7% started using testosterone between the two CTs, and 15% entered the study on testosterone and stayed on it.

Adjusting for age, race, cardiovascular risk factors, baseline serum testosterone levels, and other potential confounders, the risk of significant coronary artery calcium (CAC) progression was 2 times greater among continuous users (P = .03) and 2.4 times greater among new users (P = .01), compared with former users, who the investigators used as a control group because, at some point, they too had indications for testosterone replacement and so were more medically similar than never users.

The risk of noncalcified plaque volume progression was also more than twice as high among ongoing users, and elevated, although not significantly so, among ongoing users.

In short, “our findings are similar to those on subclinical atherosclerotic progression” in trials of older men in the general population on testosterone replacement, Dr. Haberlen said.

About half the subjects were white, 41% were at high risk for cardiovascular disease, 91% were on antiretroviral therapy, and 81% had undetectable HIV viral loads. Median total testosterone was 606 ng/dL. CAC progression was defined by incident CAC, at least a 10 Agatston unit/year increase if the baseline CAC score was 1-100, and a 10% or more annual increase if the baseline score was above 100.

Lower baseline serum testosterone was also associated with an increased risk of CAC progression, although not progression of noncalcified plaques.

The work was funded by the National Institutes of Health. Dr. Haberlen didn’t report any relevant disclosures.

[email protected]

SOURCE: Haberlen S et al. CROI 2020, Abstract 662.

Men with HIV are likely prone to the same cardiovascular risks from testosterone therapy as other men, according to new research.

There’s no reason to think they weren’t, but it hadn’t been demonstrated until now, and men with HIV are already at increased risk for cardiovascular disease. The take-home message is that “it would be prudent for clinicians to monitor closely for cardiovascular risk factors and recommend intervention to lower cardiovascular risk among men with HIV on or considering testosterone therapy,” lead investigator Sabina Haberlen, PhD, an assistant scientist in the infectious disease epidemiology division of Johns Hopkins University, Baltimore, said in a poster that was presented as part of the Conference on Retroviruses & Opportunistic Infections, which was presented online this year. CROI organizers chose to hold a virtual meeting because concerns about the spread of COVID-19.

Testosterone therapy is common among middle-aged and older men with HIV to counter the hypogonadism associated with infection. The investigators turned to the Multicenter AIDS Cohort Study – a 30-year, four-city study of HIV-1 infection in men who have sex with men – to gauge its effect.

The 300 men in the study had a baseline coronary CT angiogram in 2010-2013 and a repeat study a mean of 4.5 years later. They had no history of coronary interventions or kidney dysfunction at baseline and were aged 40-70 years, with a median age of 51 years. About 70% reported never using testosterone, 8% were former users before entering the study, 7% started using testosterone between the two CTs, and 15% entered the study on testosterone and stayed on it.

Adjusting for age, race, cardiovascular risk factors, baseline serum testosterone levels, and other potential confounders, the risk of significant coronary artery calcium (CAC) progression was 2 times greater among continuous users (P = .03) and 2.4 times greater among new users (P = .01), compared with former users, who the investigators used as a control group because, at some point, they too had indications for testosterone replacement and so were more medically similar than never users.

The risk of noncalcified plaque volume progression was also more than twice as high among ongoing users, and elevated, although not significantly so, among ongoing users.

In short, “our findings are similar to those on subclinical atherosclerotic progression” in trials of older men in the general population on testosterone replacement, Dr. Haberlen said.

About half the subjects were white, 41% were at high risk for cardiovascular disease, 91% were on antiretroviral therapy, and 81% had undetectable HIV viral loads. Median total testosterone was 606 ng/dL. CAC progression was defined by incident CAC, at least a 10 Agatston unit/year increase if the baseline CAC score was 1-100, and a 10% or more annual increase if the baseline score was above 100.

Lower baseline serum testosterone was also associated with an increased risk of CAC progression, although not progression of noncalcified plaques.

The work was funded by the National Institutes of Health. Dr. Haberlen didn’t report any relevant disclosures.

[email protected]

SOURCE: Haberlen S et al. CROI 2020, Abstract 662.

Economically, the modest safety benefit of tenofovir alafenamide-emtricitabine (Descovy) for HIV preexposure prophylaxis won’t justify paying thousands of dollars more for it when tenofovir disoproxil fumarate-emtricitabine (Truvada) becomes available as a generic in a year or so, according to a population level cost-effectiveness analysis presented at the Conference on Retroviruses & Opportunistic Infections, which was presented online this year. CROI organizers held a virtual meeting because of concerns about the spread of COVID-19.

Those benefits will translate to a health savings worth only a few hundred dollars over the likely generic price, said investigators led by Rochelle Walensky, MD, and infectious disease physician and professor of medicine at Harvard Medical School, Boston.

In a press statement, Gilead, which makes both medications, said it “strongly believes that the analysis ... is flawed, leading to inaccurate conclusions that severely underestimate the value of Descovy. The method and validation of the models, incomplete clinical data analyzed and the assumptions around potential pricing associated with a generic alternative to Truvada ... are inadequate to enable a sufficiently robust analysis.”

The company did not go into details about what exactly might have been off about the analysis.

Approved in Oct. 2019, tenofovir alafenamide-emtricitabine (also known as F/TAF) is the first new option for HIV preexposure prophylaxis (PrEP) since tenofovir disoproxil fumarate-emtricitabine (F/TDF) was approved in 2012; F/TDF is going off patent soon.

Amid a robust marketing campaign, the new medication has already captured 25% of the PrEP market, and Gilead expects up to 45% of patients to switch to F/TAF before generic F/TDF becomes available.

That worries the investigators. “At the current FSS [Federal Supply Schedule] price of $16,600 per year,” a nationwide PrEP program that uses F/TAF “would consume the entire $900.8 million federal budget for HIV prevention several times over ... If branded F/TAF drives out generic F/TDF,” rates of PrEP coverage “could decrease, and F/TAF could end up causing more avoidable HIV transmissions” than it prevents. “Given the very small, albeit statistically significant, differences in surrogate [safety] markers, without evidence of clinical significance, there is no urgency and no reason to switch PrEP regimens now,” they said. Both medications were equally effective in preventing HIV transmission in Gilead’s head-to-head phase 3 trial, but there was an a mean of about a 4 mL/min difference in estimated glomerular filtration rate at week 48 and about a 2% difference in hip and spine density at week 96, both favoring F/TAF. Marketing highlights those differences.

The investigators wanted to see how much they are worth, so they estimated savings from a possibly lower rate of bone fractures and renal failure with F/TAF and juxtaposed it with its cost and the anticipated cost of generic F/TDF at half-price, $8,300/patient-year.

They gave F/TAF the benefit of the doubt, skewing their model toward maximal harm and cost from F/TDF toxicity, and omitting the cost of increased lipid levels, weight gain, and other possible F/TAF adverse events.

In the end, they concluded that “the improved safety of F/TAF is worth no more than an additional $370 per person per year” over generic F/TDF based on toxicity differences. “Payers should consider the $370 premium ceiling estimated here in assessing whether to recommend that patients switch to F/TAF.”

The team calculated that F/TAF would prevent a maximum of 2,101 fractures and 25 cases of end-stage renal disease among 123,610 U.S. men who have sex with men treated for 5 years. That translated to an incremental cost-effectiveness ratio of more than $7 million per quality-adjusted life-year, far above the $100,000 threshold considered acceptable in the United States.

“In the presence of a generic alternative, the current price of F/TAF would have to be reduced by over $7,900/year for F/TAF to satisfy generally accepted standards of societal value. If F/TDF can achieve the 75% price reduction that is commonly observed when generic competition ensues (that is, a cost of $4,150/year), the F/TAF price would need to be no higher than $4,520 to demonstrate value on the basis of cost-effectiveness,” the investigators said.

For older patients at unusually high risk for renal disease or bone-related adverse events, the switch from F/TDF to F/TAF would have greater clinical effect and benefit. Even in this population, however, it would be difficult to defend a price greater than $800 over the cost of the generic alternative,” they said.

“The message seems clear that the current cost of F/TAF does not justify wholesale conversion to F/TAF as the first-line agent for all PrEP-eligible patients,” said Carlos del Rio, MD, and Wendy Armstrong, MD, infectious disease professors at Emory University, Atlanta, in an editorial. “For PrEP-eligible persons at low risk for fracture and renal disease, it is very hard to justify use of F/TAF knowing that F/TDF will soon be generic” (Ann Intern Med. 2020 Mar 10. doi: 10.7326/M20-0799).

“Successful PrEP scale-up in other countries was made possible by drug costs that are less than $100/month in most countries. In the United States, without drastic reductions in the cost of PrEP, which may be achievable with generic F/TDF ... we will fail to avert otherwise preventable new HIV transmissions,” they said.

The study was simultaneously published online (Ann Intern Med. 2020 Mar 10. doi: 10.7326/M19-3478).

The work was funded by the National Institutes of Health and Massachusetts General Hospital. The investigators and editorialists didn’t have any industry disclosures.

[email protected]

SOURCE: Walensky RP et al. Ann Intern Med. 2020 Mar 10. doi: 10.7326/M19-3478.

Economically, the modest safety benefit of tenofovir alafenamide-emtricitabine (Descovy) for HIV preexposure prophylaxis won’t justify paying thousands of dollars more for it when tenofovir disoproxil fumarate-emtricitabine (Truvada) becomes available as a generic in a year or so, according to a population level cost-effectiveness analysis presented at the Conference on Retroviruses & Opportunistic Infections, which was presented online this year. CROI organizers held a virtual meeting because of concerns about the spread of COVID-19.

Those benefits will translate to a health savings worth only a few hundred dollars over the likely generic price, said investigators led by Rochelle Walensky, MD, and infectious disease physician and professor of medicine at Harvard Medical School, Boston.

In a press statement, Gilead, which makes both medications, said it “strongly believes that the analysis ... is flawed, leading to inaccurate conclusions that severely underestimate the value of Descovy. The method and validation of the models, incomplete clinical data analyzed and the assumptions around potential pricing associated with a generic alternative to Truvada ... are inadequate to enable a sufficiently robust analysis.”

The company did not go into details about what exactly might have been off about the analysis.

Approved in Oct. 2019, tenofovir alafenamide-emtricitabine (also known as F/TAF) is the first new option for HIV preexposure prophylaxis (PrEP) since tenofovir disoproxil fumarate-emtricitabine (F/TDF) was approved in 2012; F/TDF is going off patent soon.

Amid a robust marketing campaign, the new medication has already captured 25% of the PrEP market, and Gilead expects up to 45% of patients to switch to F/TAF before generic F/TDF becomes available.

That worries the investigators. “At the current FSS [Federal Supply Schedule] price of $16,600 per year,” a nationwide PrEP program that uses F/TAF “would consume the entire $900.8 million federal budget for HIV prevention several times over ... If branded F/TAF drives out generic F/TDF,” rates of PrEP coverage “could decrease, and F/TAF could end up causing more avoidable HIV transmissions” than it prevents. “Given the very small, albeit statistically significant, differences in surrogate [safety] markers, without evidence of clinical significance, there is no urgency and no reason to switch PrEP regimens now,” they said. Both medications were equally effective in preventing HIV transmission in Gilead’s head-to-head phase 3 trial, but there was an a mean of about a 4 mL/min difference in estimated glomerular filtration rate at week 48 and about a 2% difference in hip and spine density at week 96, both favoring F/TAF. Marketing highlights those differences.

The investigators wanted to see how much they are worth, so they estimated savings from a possibly lower rate of bone fractures and renal failure with F/TAF and juxtaposed it with its cost and the anticipated cost of generic F/TDF at half-price, $8,300/patient-year.

They gave F/TAF the benefit of the doubt, skewing their model toward maximal harm and cost from F/TDF toxicity, and omitting the cost of increased lipid levels, weight gain, and other possible F/TAF adverse events.

In the end, they concluded that “the improved safety of F/TAF is worth no more than an additional $370 per person per year” over generic F/TDF based on toxicity differences. “Payers should consider the $370 premium ceiling estimated here in assessing whether to recommend that patients switch to F/TAF.”

The team calculated that F/TAF would prevent a maximum of 2,101 fractures and 25 cases of end-stage renal disease among 123,610 U.S. men who have sex with men treated for 5 years. That translated to an incremental cost-effectiveness ratio of more than $7 million per quality-adjusted life-year, far above the $100,000 threshold considered acceptable in the United States.

“In the presence of a generic alternative, the current price of F/TAF would have to be reduced by over $7,900/year for F/TAF to satisfy generally accepted standards of societal value. If F/TDF can achieve the 75% price reduction that is commonly observed when generic competition ensues (that is, a cost of $4,150/year), the F/TAF price would need to be no higher than $4,520 to demonstrate value on the basis of cost-effectiveness,” the investigators said.

For older patients at unusually high risk for renal disease or bone-related adverse events, the switch from F/TDF to F/TAF would have greater clinical effect and benefit. Even in this population, however, it would be difficult to defend a price greater than $800 over the cost of the generic alternative,” they said.

“The message seems clear that the current cost of F/TAF does not justify wholesale conversion to F/TAF as the first-line agent for all PrEP-eligible patients,” said Carlos del Rio, MD, and Wendy Armstrong, MD, infectious disease professors at Emory University, Atlanta, in an editorial. “For PrEP-eligible persons at low risk for fracture and renal disease, it is very hard to justify use of F/TAF knowing that F/TDF will soon be generic” (Ann Intern Med. 2020 Mar 10. doi: 10.7326/M20-0799).

“Successful PrEP scale-up in other countries was made possible by drug costs that are less than $100/month in most countries. In the United States, without drastic reductions in the cost of PrEP, which may be achievable with generic F/TDF ... we will fail to avert otherwise preventable new HIV transmissions,” they said.

The study was simultaneously published online (Ann Intern Med. 2020 Mar 10. doi: 10.7326/M19-3478).

The work was funded by the National Institutes of Health and Massachusetts General Hospital. The investigators and editorialists didn’t have any industry disclosures.

[email protected]

SOURCE: Walensky RP et al. Ann Intern Med. 2020 Mar 10. doi: 10.7326/M19-3478.

Economically, the modest safety benefit of tenofovir alafenamide-emtricitabine (Descovy) for HIV preexposure prophylaxis won’t justify paying thousands of dollars more for it when tenofovir disoproxil fumarate-emtricitabine (Truvada) becomes available as a generic in a year or so, according to a population level cost-effectiveness analysis presented at the Conference on Retroviruses & Opportunistic Infections, which was presented online this year. CROI organizers held a virtual meeting because of concerns about the spread of COVID-19.

Those benefits will translate to a health savings worth only a few hundred dollars over the likely generic price, said investigators led by Rochelle Walensky, MD, and infectious disease physician and professor of medicine at Harvard Medical School, Boston.

In a press statement, Gilead, which makes both medications, said it “strongly believes that the analysis ... is flawed, leading to inaccurate conclusions that severely underestimate the value of Descovy. The method and validation of the models, incomplete clinical data analyzed and the assumptions around potential pricing associated with a generic alternative to Truvada ... are inadequate to enable a sufficiently robust analysis.”

The company did not go into details about what exactly might have been off about the analysis.

Approved in Oct. 2019, tenofovir alafenamide-emtricitabine (also known as F/TAF) is the first new option for HIV preexposure prophylaxis (PrEP) since tenofovir disoproxil fumarate-emtricitabine (F/TDF) was approved in 2012; F/TDF is going off patent soon.

Amid a robust marketing campaign, the new medication has already captured 25% of the PrEP market, and Gilead expects up to 45% of patients to switch to F/TAF before generic F/TDF becomes available.

That worries the investigators. “At the current FSS [Federal Supply Schedule] price of $16,600 per year,” a nationwide PrEP program that uses F/TAF “would consume the entire $900.8 million federal budget for HIV prevention several times over ... If branded F/TAF drives out generic F/TDF,” rates of PrEP coverage “could decrease, and F/TAF could end up causing more avoidable HIV transmissions” than it prevents. “Given the very small, albeit statistically significant, differences in surrogate [safety] markers, without evidence of clinical significance, there is no urgency and no reason to switch PrEP regimens now,” they said. Both medications were equally effective in preventing HIV transmission in Gilead’s head-to-head phase 3 trial, but there was an a mean of about a 4 mL/min difference in estimated glomerular filtration rate at week 48 and about a 2% difference in hip and spine density at week 96, both favoring F/TAF. Marketing highlights those differences.

The investigators wanted to see how much they are worth, so they estimated savings from a possibly lower rate of bone fractures and renal failure with F/TAF and juxtaposed it with its cost and the anticipated cost of generic F/TDF at half-price, $8,300/patient-year.

They gave F/TAF the benefit of the doubt, skewing their model toward maximal harm and cost from F/TDF toxicity, and omitting the cost of increased lipid levels, weight gain, and other possible F/TAF adverse events.

In the end, they concluded that “the improved safety of F/TAF is worth no more than an additional $370 per person per year” over generic F/TDF based on toxicity differences. “Payers should consider the $370 premium ceiling estimated here in assessing whether to recommend that patients switch to F/TAF.”

The team calculated that F/TAF would prevent a maximum of 2,101 fractures and 25 cases of end-stage renal disease among 123,610 U.S. men who have sex with men treated for 5 years. That translated to an incremental cost-effectiveness ratio of more than $7 million per quality-adjusted life-year, far above the $100,000 threshold considered acceptable in the United States.

“In the presence of a generic alternative, the current price of F/TAF would have to be reduced by over $7,900/year for F/TAF to satisfy generally accepted standards of societal value. If F/TDF can achieve the 75% price reduction that is commonly observed when generic competition ensues (that is, a cost of $4,150/year), the F/TAF price would need to be no higher than $4,520 to demonstrate value on the basis of cost-effectiveness,” the investigators said.

For older patients at unusually high risk for renal disease or bone-related adverse events, the switch from F/TDF to F/TAF would have greater clinical effect and benefit. Even in this population, however, it would be difficult to defend a price greater than $800 over the cost of the generic alternative,” they said.

“The message seems clear that the current cost of F/TAF does not justify wholesale conversion to F/TAF as the first-line agent for all PrEP-eligible patients,” said Carlos del Rio, MD, and Wendy Armstrong, MD, infectious disease professors at Emory University, Atlanta, in an editorial. “For PrEP-eligible persons at low risk for fracture and renal disease, it is very hard to justify use of F/TAF knowing that F/TDF will soon be generic” (Ann Intern Med. 2020 Mar 10. doi: 10.7326/M20-0799).

“Successful PrEP scale-up in other countries was made possible by drug costs that are less than $100/month in most countries. In the United States, without drastic reductions in the cost of PrEP, which may be achievable with generic F/TDF ... we will fail to avert otherwise preventable new HIV transmissions,” they said.

The study was simultaneously published online (Ann Intern Med. 2020 Mar 10. doi: 10.7326/M19-3478).

The work was funded by the National Institutes of Health and Massachusetts General Hospital. The investigators and editorialists didn’t have any industry disclosures.

[email protected]

SOURCE: Walensky RP et al. Ann Intern Med. 2020 Mar 10. doi: 10.7326/M19-3478.

Two international phase 3 randomized trials of injections of long-acting suspensions of cabotegravir and rilpivirine show promise for the control of HIV, according to reports published in the New England Journal of Medicine.

© Dr. A. Harrison; Dr. P. Feorino / CDC

The Long-Acting Cabotegravir and Rilpivirine after Oral Induction for HIV-1 Infection (FLAIR) study and the Long-Acting Cabotegravir and Rilpivirine for Maintenance of HIV-1 Suppression (ATLAS) study looked at a separate facet of the use of a monthly therapeutic injection as a replacement for daily oral HIV therapy.

The FLAIR trial (ClinicalTrials.gov number, NCT02938520) was a phase 3, randomized, open-label study in which adults with HIV-1 infection who had not previously received antiretroviral therapy were given 20 weeks of daily oral induction therapy with dolutegravir–abacavir–lamivudine. Those patients with an HIV-1 RNA level of less than 50 copies per milliliter after 16 weeks were then randomly assigned (1:1) to continue their current oral therapy or switch to oral cabotegravir plus rilpivirine for 1 month followed by monthly intramuscular injections of long-acting cabotegravir, an HIV-1 integrase strand-transfer inhibitor, and rilpivirine, a nonnucleoside reverse-transcriptase inhibitor.

At week 48, an HIV-1 RNA level of 50 copies per milliliter or higher was found in 6 of 283 patients (2.1%) who received the long-acting therapy and in 7 of 283 (2.5%) who received oral therapy, which met the criterion for noninferiority for the primary endpoint. An HIV-1 RNA level of less than 50 copies per milliliter at week 48 was found in 93.6% of patients who received long-acting therapy and in 93.3% who received oral therapy, which also met the criterion for noninferiority, according to the study published in the New England Journal of Medicine.

Injection site reactions were reported in 86% of the long-acting therapy patients, 4 of whom withdrew from the trial for injection-related reasons. Grade 3 or higher adverse events and events that met liver-related stopping criteria occurred in 11% and 2%, respectively, of those who received long-acting therapy and in 4% and 1% of those who received oral therapy.

An assessment of treatment satisfaction at 48 weeks showed that 91% of the patients who switched to long-acting therapy preferred it to their daily oral therapy.

The ATLAS trial (ClinicalTrials.gov number, NCT02951052) was a phase 3, open-label, multicenter, noninferiority trial involving patients who had plasma HIV-1 RNA levels of less than 50 copies per milliliter for at least 6 months while taking standard oral antiretroviral therapy. These patients were randomized (308 in each group) to the long-acting cabotegravir plus rilpivirine injection therapy or daily oral therapy.

At 48 weeks, HIV-1 RNA levels of 50 copies per milliliter or higher were found in five participants (1.6%) receiving long-acting therapy and in three (1.0%) receiving oral therapy, which met the criterion for noninferiority for the primary endpoint, according to a study reported in the New England Journal of Medicine.

HIV-1 RNA levels of less than 50 copies per milliliter at week 48 occurred in 92.5% of patients on long-acting therapy and in 95.5% of those receiving oral therapy, which also met the criterion for noninferiority for this endpoint. Three patients in the long-acting therapy group had virologic failure, compared with four participants who received oral therapy.

Adverse events were more common in the long-acting–therapy group and included injection-site pain, which occurred in 231 recipients (75%) of long-acting therapy. This was mild or moderate in most cases, according to the authors. However, 1% of the participants in this group withdrew because of it. Overall, serious adverse events were reported in no more than 5% of participants in each group.

Together, the ATLAS and the FLAIR trials show that long-acting intramuscular injection therapy is noninferior to oral therapy as both an early regimen for HIV treatment, as well as for later, maintenance dosing. The use of long-acting therapy may improve patient adherence to treatment, according to both sets of study authors.

The ATLAS and FLAIR trials were funded by ViiV Healthcare and Janssen. The authors of both studies reported ties to pharmaceutical associations, and some authors are employees of the two funding sources.

[email protected]

SOURCE: Orkin C et al. N Engl J Med. 2020 Mar 4. doi: 10.1056/NEJMoa1909512 and Swindells S et al. N Engl J Med. 2020 Mar 4. doi: 10.1056/NEJMoa1904398.

Two international phase 3 randomized trials of injections of long-acting suspensions of cabotegravir and rilpivirine show promise for the control of HIV, according to reports published in the New England Journal of Medicine.

© Dr. A. Harrison; Dr. P. Feorino / CDC

The Long-Acting Cabotegravir and Rilpivirine after Oral Induction for HIV-1 Infection (FLAIR) study and the Long-Acting Cabotegravir and Rilpivirine for Maintenance of HIV-1 Suppression (ATLAS) study looked at a separate facet of the use of a monthly therapeutic injection as a replacement for daily oral HIV therapy.

The FLAIR trial (ClinicalTrials.gov number, NCT02938520) was a phase 3, randomized, open-label study in which adults with HIV-1 infection who had not previously received antiretroviral therapy were given 20 weeks of daily oral induction therapy with dolutegravir–abacavir–lamivudine. Those patients with an HIV-1 RNA level of less than 50 copies per milliliter after 16 weeks were then randomly assigned (1:1) to continue their current oral therapy or switch to oral cabotegravir plus rilpivirine for 1 month followed by monthly intramuscular injections of long-acting cabotegravir, an HIV-1 integrase strand-transfer inhibitor, and rilpivirine, a nonnucleoside reverse-transcriptase inhibitor.

At week 48, an HIV-1 RNA level of 50 copies per milliliter or higher was found in 6 of 283 patients (2.1%) who received the long-acting therapy and in 7 of 283 (2.5%) who received oral therapy, which met the criterion for noninferiority for the primary endpoint. An HIV-1 RNA level of less than 50 copies per milliliter at week 48 was found in 93.6% of patients who received long-acting therapy and in 93.3% who received oral therapy, which also met the criterion for noninferiority, according to the study published in the New England Journal of Medicine.

Injection site reactions were reported in 86% of the long-acting therapy patients, 4 of whom withdrew from the trial for injection-related reasons. Grade 3 or higher adverse events and events that met liver-related stopping criteria occurred in 11% and 2%, respectively, of those who received long-acting therapy and in 4% and 1% of those who received oral therapy.

An assessment of treatment satisfaction at 48 weeks showed that 91% of the patients who switched to long-acting therapy preferred it to their daily oral therapy.

The ATLAS trial (ClinicalTrials.gov number, NCT02951052) was a phase 3, open-label, multicenter, noninferiority trial involving patients who had plasma HIV-1 RNA levels of less than 50 copies per milliliter for at least 6 months while taking standard oral antiretroviral therapy. These patients were randomized (308 in each group) to the long-acting cabotegravir plus rilpivirine injection therapy or daily oral therapy.

At 48 weeks, HIV-1 RNA levels of 50 copies per milliliter or higher were found in five participants (1.6%) receiving long-acting therapy and in three (1.0%) receiving oral therapy, which met the criterion for noninferiority for the primary endpoint, according to a study reported in the New England Journal of Medicine.

HIV-1 RNA levels of less than 50 copies per milliliter at week 48 occurred in 92.5% of patients on long-acting therapy and in 95.5% of those receiving oral therapy, which also met the criterion for noninferiority for this endpoint. Three patients in the long-acting therapy group had virologic failure, compared with four participants who received oral therapy.

Adverse events were more common in the long-acting–therapy group and included injection-site pain, which occurred in 231 recipients (75%) of long-acting therapy. This was mild or moderate in most cases, according to the authors. However, 1% of the participants in this group withdrew because of it. Overall, serious adverse events were reported in no more than 5% of participants in each group.

Together, the ATLAS and the FLAIR trials show that long-acting intramuscular injection therapy is noninferior to oral therapy as both an early regimen for HIV treatment, as well as for later, maintenance dosing. The use of long-acting therapy may improve patient adherence to treatment, according to both sets of study authors.

The ATLAS and FLAIR trials were funded by ViiV Healthcare and Janssen. The authors of both studies reported ties to pharmaceutical associations, and some authors are employees of the two funding sources.

[email protected]

SOURCE: Orkin C et al. N Engl J Med. 2020 Mar 4. doi: 10.1056/NEJMoa1909512 and Swindells S et al. N Engl J Med. 2020 Mar 4. doi: 10.1056/NEJMoa1904398.

Two international phase 3 randomized trials of injections of long-acting suspensions of cabotegravir and rilpivirine show promise for the control of HIV, according to reports published in the New England Journal of Medicine.

© Dr. A. Harrison; Dr. P. Feorino / CDC

The Long-Acting Cabotegravir and Rilpivirine after Oral Induction for HIV-1 Infection (FLAIR) study and the Long-Acting Cabotegravir and Rilpivirine for Maintenance of HIV-1 Suppression (ATLAS) study looked at a separate facet of the use of a monthly therapeutic injection as a replacement for daily oral HIV therapy.

The FLAIR trial (ClinicalTrials.gov number, NCT02938520) was a phase 3, randomized, open-label study in which adults with HIV-1 infection who had not previously received antiretroviral therapy were given 20 weeks of daily oral induction therapy with dolutegravir–abacavir–lamivudine. Those patients with an HIV-1 RNA level of less than 50 copies per milliliter after 16 weeks were then randomly assigned (1:1) to continue their current oral therapy or switch to oral cabotegravir plus rilpivirine for 1 month followed by monthly intramuscular injections of long-acting cabotegravir, an HIV-1 integrase strand-transfer inhibitor, and rilpivirine, a nonnucleoside reverse-transcriptase inhibitor.

At week 48, an HIV-1 RNA level of 50 copies per milliliter or higher was found in 6 of 283 patients (2.1%) who received the long-acting therapy and in 7 of 283 (2.5%) who received oral therapy, which met the criterion for noninferiority for the primary endpoint. An HIV-1 RNA level of less than 50 copies per milliliter at week 48 was found in 93.6% of patients who received long-acting therapy and in 93.3% who received oral therapy, which also met the criterion for noninferiority, according to the study published in the New England Journal of Medicine.

Injection site reactions were reported in 86% of the long-acting therapy patients, 4 of whom withdrew from the trial for injection-related reasons. Grade 3 or higher adverse events and events that met liver-related stopping criteria occurred in 11% and 2%, respectively, of those who received long-acting therapy and in 4% and 1% of those who received oral therapy.

An assessment of treatment satisfaction at 48 weeks showed that 91% of the patients who switched to long-acting therapy preferred it to their daily oral therapy.

The ATLAS trial (ClinicalTrials.gov number, NCT02951052) was a phase 3, open-label, multicenter, noninferiority trial involving patients who had plasma HIV-1 RNA levels of less than 50 copies per milliliter for at least 6 months while taking standard oral antiretroviral therapy. These patients were randomized (308 in each group) to the long-acting cabotegravir plus rilpivirine injection therapy or daily oral therapy.

At 48 weeks, HIV-1 RNA levels of 50 copies per milliliter or higher were found in five participants (1.6%) receiving long-acting therapy and in three (1.0%) receiving oral therapy, which met the criterion for noninferiority for the primary endpoint, according to a study reported in the New England Journal of Medicine.

HIV-1 RNA levels of less than 50 copies per milliliter at week 48 occurred in 92.5% of patients on long-acting therapy and in 95.5% of those receiving oral therapy, which also met the criterion for noninferiority for this endpoint. Three patients in the long-acting therapy group had virologic failure, compared with four participants who received oral therapy.

Adverse events were more common in the long-acting–therapy group and included injection-site pain, which occurred in 231 recipients (75%) of long-acting therapy. This was mild or moderate in most cases, according to the authors. However, 1% of the participants in this group withdrew because of it. Overall, serious adverse events were reported in no more than 5% of participants in each group.

Together, the ATLAS and the FLAIR trials show that long-acting intramuscular injection therapy is noninferior to oral therapy as both an early regimen for HIV treatment, as well as for later, maintenance dosing. The use of long-acting therapy may improve patient adherence to treatment, according to both sets of study authors.

The ATLAS and FLAIR trials were funded by ViiV Healthcare and Janssen. The authors of both studies reported ties to pharmaceutical associations, and some authors are employees of the two funding sources.

[email protected]

SOURCE: Orkin C et al. N Engl J Med. 2020 Mar 4. doi: 10.1056/NEJMoa1909512 and Swindells S et al. N Engl J Med. 2020 Mar 4. doi: 10.1056/NEJMoa1904398.

Hepatitis C virus (HCV) is known to be a common sexually transmitted infection (STI) among HIV-positive men who have sex with men (MSM). To examine this relationship in HIV-negative MSM, researchers in the Amsterdam PrEP Project team in the HIV Transmission Elimination AMsterdam (H-TEAM) Initiative evaluated HCV-incidence and its risk-factors in this population, who were using pre-exposure prophylaxis (PrEP).

Participants in the Amsterdam PrEP project were tested for HCV antibodies or HCV-RNA every 6 months. During the period, participants used daily or event-driven PrEP and could switch regimens during follow-up, according to the report by published in the Journal of Hepatology. 
HIV-negative MSM on PrEP are at risk for incident HCV-infection, while identified risk-factors are similar to those in HIV-positive MSM. 

Among 350 participants, they detected 15 HCV infections in 14 participants, finding 8 primary infections and 7 reinfections. The researchers found that the factors associated with incident HCV-infection were higher number of receptive condomless anal sex acts with casual partners, anal STI, injecting drug use, and sharing straws when snorting drugs. These are similar risk-factors  to those found among in HIV-positive MSM.

They concluded that, because HIV-negative MSM on PrEP are at risk for incident HCV-infection, regular HCV-testing was needed, especially for those with a previous HCV-infection.

Hepatitis C virus (HCV) is known to be a common sexually transmitted infection (STI) among HIV-positive men who have sex with men (MSM). To examine this relationship in HIV-negative MSM, researchers in the Amsterdam PrEP Project team in the HIV Transmission Elimination AMsterdam (H-TEAM) Initiative evaluated HCV-incidence and its risk-factors in this population, who were using pre-exposure prophylaxis (PrEP).

Participants in the Amsterdam PrEP project were tested for HCV antibodies or HCV-RNA every 6 months. During the period, participants used daily or event-driven PrEP and could switch regimens during follow-up, according to the report by published in the Journal of Hepatology. 
HIV-negative MSM on PrEP are at risk for incident HCV-infection, while identified risk-factors are similar to those in HIV-positive MSM. 

Among 350 participants, they detected 15 HCV infections in 14 participants, finding 8 primary infections and 7 reinfections. The researchers found that the factors associated with incident HCV-infection were higher number of receptive condomless anal sex acts with casual partners, anal STI, injecting drug use, and sharing straws when snorting drugs. These are similar risk-factors  to those found among in HIV-positive MSM.

They concluded that, because HIV-negative MSM on PrEP are at risk for incident HCV-infection, regular HCV-testing was needed, especially for those with a previous HCV-infection.

Hepatitis C virus (HCV) is known to be a common sexually transmitted infection (STI) among HIV-positive men who have sex with men (MSM). To examine this relationship in HIV-negative MSM, researchers in the Amsterdam PrEP Project team in the HIV Transmission Elimination AMsterdam (H-TEAM) Initiative evaluated HCV-incidence and its risk-factors in this population, who were using pre-exposure prophylaxis (PrEP).

Participants in the Amsterdam PrEP project were tested for HCV antibodies or HCV-RNA every 6 months. During the period, participants used daily or event-driven PrEP and could switch regimens during follow-up, according to the report by published in the Journal of Hepatology. 
HIV-negative MSM on PrEP are at risk for incident HCV-infection, while identified risk-factors are similar to those in HIV-positive MSM. 

Among 350 participants, they detected 15 HCV infections in 14 participants, finding 8 primary infections and 7 reinfections. The researchers found that the factors associated with incident HCV-infection were higher number of receptive condomless anal sex acts with casual partners, anal STI, injecting drug use, and sharing straws when snorting drugs. These are similar risk-factors  to those found among in HIV-positive MSM.

They concluded that, because HIV-negative MSM on PrEP are at risk for incident HCV-infection, regular HCV-testing was needed, especially for those with a previous HCV-infection.

I recently was on a panel of experts discussing how to prevent HIV among transgender youth. Preventing HIV among transgender youth, especially transgender youth of color, remains a challenge for multiple reasons – racism, poverty, stigma, marginalization, and discrimination play a role in the HIV epidemic. A barrier to preventing HIV infections among transgender youth is a lack of knowledge on how to provide them with comprehensive sexual and reproductive health care. Here are some tips and resources that can help you ensure that transgender youth are safe and healthy.

sturti/E+

One of the challenges of obtaining a sexual history is asking the right questions to illicit the appropriate history: Focus on organs and activities instead of gender. For example, if you have a transgender male assigned female at birth, ask whether their partners produce sperm instead of asking about the sex of their partners. A transgender male’s partner may identify as female but is assigned male at birth and uses her penis during sex. Furthermore, a transgender male may be on testosterone, but he still can get pregnant. Asking how they use their organs is just as important. A transgender male who has condomless penile-vaginal sex with multiple partners is at a higher risk for HIV infection than is a transgender male who shares sex toys with his only partner.

Normalizing that you ask a comprehensive sexual history to all your patients regardless of gender identity may put the patient at ease. Many transgender people are reluctant to disclose their gender identity to their provider because they are afraid that the provider may fixate on their sexuality once they do. Stating that you ask sexual health questions to all your patients may prevent the transgender patient from feeling singled out.

Finally, you don’t have to ask a sexual history with every transgender patient, just as you wouldn’t for your cisgender patients. If a patient is complaining of a sprained ankle, a sexual history may not be helpful, compared with obtaining one when a patient comes in with pelvic pain. Many transgender patients avoid care because they are frequently asked about their sexual history or gender identity when these are not relevant to their chief complaint.

Here are some helpful questions to ask when taking a sexual history, according to the University of California, San Francisco, Transgender Care & Treatment Guidelines.¹

• Are you having sex? How many sex partners have you had in the past year?
• Who are you having sex with? What types of sex are you having? What parts of your anatomy do you use for sex?
• How do you protect yourself from STIs?
• What STIs have you had in the past, if any? When were you last tested for STIs?
• Has your partner(s) ever been diagnosed with any STIs?
• Do you use alcohol or any drugs when you have sex?
• Do you exchange sex for money, drugs, or a place to stay?

Also, use a trauma-informed approach when working with transgender patients. Many have been victims of sexual trauma. Always have a chaperone accompany you during the exam, explain to the patient what you plan to do and why it is necessary, and allow them to decline (and document their declining the physical exam). Also consider having your patient self-swab for STI screening if appropriate.¹

Like obtaining a sexual history, routine screenings for certain types of cancers will be based on the organs the patient has. For example, a transgender woman assigned male at birth will not need a cervical cancer screening, but a transgender man assigned female at birth may need one – if the patient still has a cervix. Cervical cancer screening guidelines are similar for transgender men as it is for nontransgender women, and one should use the same guidelines endorsed by the American Cancer Society, American Society of Colposcopy and Cervical Pathology, American Society of Clinical Pathologists, U.S. Preventive Services Task Force, and the World Health Organization.^2-4

Cervical screenings should never be a requirement for testosterone therapy, and no transgender male under the age of 21 years will need cervical screening. The University of California guidelines offers tips on how to make transgender men more comfortable during cervical cancer screening.⁵

Contraception and menstrual management also are important for transgender patients. Testosterone can induce amenorrhea for transgender men, but it is not good birth control. If a transgender male patient has sex with partners that produce sperm, then the physician should discuss effective birth control options. There is no ideal birth control option for transgender men. One must consider multiple factors including the patient’s desire for pregnancy, desire to cease periods, ease of administration, and risk for thrombosis.

Most transgender men may balk at the idea of taking estrogen-containing contraception, but it is more effective than oral progestin-only pills. Intrauterine devices are highly effective in pregnancy prevention and can achieve amenorrhea in 50% of users within 1 year,but some transmen may become dysphoric with the procedure. ⁶ The etonogestrel implants also are highly effective birth control, but irregular periods are common, leading to discontinuation. Depot medroxyprogesterone is highly effective in preventing pregnancy and can induce amenorrhea in 70% of users within 1 year and 80% of users in 2 years, but also is associated with weight gain in one-third of users.⁷ Finally, pubertal blockers can rapidly stop periods for transmen who are severely dysphoric from their menses; however, before achieving amenorrhea, a flare bleed can occur 4-6 weeks after administration.⁸ Support from a mental health therapist during this time is critical. Pubertal blockers, nevertheless, are not suitable birth control.

When providing affirming sexual and reproductive health care for transgender patients, key principles include focusing on organs and activities over identity. Additionally, screening for certain types of cancers also is dependent on organs. Finally, do not neglect the importance of contraception among transgender men. Taking these principles in consideration will help you provide excellent care for transgender youth.

Dr. Montano is an assistant professor of pediatrics at the University of Pittsburgh and an adolescent medicine physician at the Children’s Hospital of Pittsburgh. He said he had no relevant financial disclosures. Email him at [email protected].

References

1. Transgender people and sexually transmitted infections (https://transcare.ucsf.edu/guidelines/stis).

2. CA Cancer J Clin. 2012 May-Jun;62(3):147-72.

3. Ann Intern Med. 2012;156(12):880-91.

4. Cervical cancer screening in developing countries: Report of a WHO consultation. 2002. World Health Organization, Geneva.

5. Screening for cervical cancer for transgender men (https://transcare.ucsf.edu/guidelines/cervical-cancer).

6. Contraception. 2002 Feb;65(2):129-32.

7. Rev Endocr Metab Disord. 2011 Jun;12(2):93-106.

8. Int J Womens Health. 2014 Jun 23;6:631-7.

Resources

Breast cancer screening in transgender men. (https://transcare.ucsf.edu/guidelines/breast-cancer-men).

Screening for breast cancer in transgender women. (https://transcare.ucsf.edu/guidelines/breast-cancer-women).

Transgender health and HIV (https://transcare.ucsf.edu/guidelines/hiv).

Centers for Disease Control and Prevention: HIV and Transgender People (https://www.cdc.gov/hiv/group/gender/transgender/index.html).

I recently was on a panel of experts discussing how to prevent HIV among transgender youth. Preventing HIV among transgender youth, especially transgender youth of color, remains a challenge for multiple reasons – racism, poverty, stigma, marginalization, and discrimination play a role in the HIV epidemic. A barrier to preventing HIV infections among transgender youth is a lack of knowledge on how to provide them with comprehensive sexual and reproductive health care. Here are some tips and resources that can help you ensure that transgender youth are safe and healthy.

sturti/E+

One of the challenges of obtaining a sexual history is asking the right questions to illicit the appropriate history: Focus on organs and activities instead of gender. For example, if you have a transgender male assigned female at birth, ask whether their partners produce sperm instead of asking about the sex of their partners. A transgender male’s partner may identify as female but is assigned male at birth and uses her penis during sex. Furthermore, a transgender male may be on testosterone, but he still can get pregnant. Asking how they use their organs is just as important. A transgender male who has condomless penile-vaginal sex with multiple partners is at a higher risk for HIV infection than is a transgender male who shares sex toys with his only partner.

Normalizing that you ask a comprehensive sexual history to all your patients regardless of gender identity may put the patient at ease. Many transgender people are reluctant to disclose their gender identity to their provider because they are afraid that the provider may fixate on their sexuality once they do. Stating that you ask sexual health questions to all your patients may prevent the transgender patient from feeling singled out.

Finally, you don’t have to ask a sexual history with every transgender patient, just as you wouldn’t for your cisgender patients. If a patient is complaining of a sprained ankle, a sexual history may not be helpful, compared with obtaining one when a patient comes in with pelvic pain. Many transgender patients avoid care because they are frequently asked about their sexual history or gender identity when these are not relevant to their chief complaint.

Here are some helpful questions to ask when taking a sexual history, according to the University of California, San Francisco, Transgender Care & Treatment Guidelines.¹

• Are you having sex? How many sex partners have you had in the past year?
• Who are you having sex with? What types of sex are you having? What parts of your anatomy do you use for sex?
• How do you protect yourself from STIs?
• What STIs have you had in the past, if any? When were you last tested for STIs?
• Has your partner(s) ever been diagnosed with any STIs?
• Do you use alcohol or any drugs when you have sex?
• Do you exchange sex for money, drugs, or a place to stay?

Also, use a trauma-informed approach when working with transgender patients. Many have been victims of sexual trauma. Always have a chaperone accompany you during the exam, explain to the patient what you plan to do and why it is necessary, and allow them to decline (and document their declining the physical exam). Also consider having your patient self-swab for STI screening if appropriate.¹

Like obtaining a sexual history, routine screenings for certain types of cancers will be based on the organs the patient has. For example, a transgender woman assigned male at birth will not need a cervical cancer screening, but a transgender man assigned female at birth may need one – if the patient still has a cervix. Cervical cancer screening guidelines are similar for transgender men as it is for nontransgender women, and one should use the same guidelines endorsed by the American Cancer Society, American Society of Colposcopy and Cervical Pathology, American Society of Clinical Pathologists, U.S. Preventive Services Task Force, and the World Health Organization.^2-4

Cervical screenings should never be a requirement for testosterone therapy, and no transgender male under the age of 21 years will need cervical screening. The University of California guidelines offers tips on how to make transgender men more comfortable during cervical cancer screening.⁵

Contraception and menstrual management also are important for transgender patients. Testosterone can induce amenorrhea for transgender men, but it is not good birth control. If a transgender male patient has sex with partners that produce sperm, then the physician should discuss effective birth control options. There is no ideal birth control option for transgender men. One must consider multiple factors including the patient’s desire for pregnancy, desire to cease periods, ease of administration, and risk for thrombosis.

Most transgender men may balk at the idea of taking estrogen-containing contraception, but it is more effective than oral progestin-only pills. Intrauterine devices are highly effective in pregnancy prevention and can achieve amenorrhea in 50% of users within 1 year,but some transmen may become dysphoric with the procedure. ⁶ The etonogestrel implants also are highly effective birth control, but irregular periods are common, leading to discontinuation. Depot medroxyprogesterone is highly effective in preventing pregnancy and can induce amenorrhea in 70% of users within 1 year and 80% of users in 2 years, but also is associated with weight gain in one-third of users.⁷ Finally, pubertal blockers can rapidly stop periods for transmen who are severely dysphoric from their menses; however, before achieving amenorrhea, a flare bleed can occur 4-6 weeks after administration.⁸ Support from a mental health therapist during this time is critical. Pubertal blockers, nevertheless, are not suitable birth control.

When providing affirming sexual and reproductive health care for transgender patients, key principles include focusing on organs and activities over identity. Additionally, screening for certain types of cancers also is dependent on organs. Finally, do not neglect the importance of contraception among transgender men. Taking these principles in consideration will help you provide excellent care for transgender youth.

Dr. Montano is an assistant professor of pediatrics at the University of Pittsburgh and an adolescent medicine physician at the Children’s Hospital of Pittsburgh. He said he had no relevant financial disclosures. Email him at [email protected].

References

1. Transgender people and sexually transmitted infections (https://transcare.ucsf.edu/guidelines/stis).

2. CA Cancer J Clin. 2012 May-Jun;62(3):147-72.

3. Ann Intern Med. 2012;156(12):880-91.

4. Cervical cancer screening in developing countries: Report of a WHO consultation. 2002. World Health Organization, Geneva.

5. Screening for cervical cancer for transgender men (https://transcare.ucsf.edu/guidelines/cervical-cancer).

6. Contraception. 2002 Feb;65(2):129-32.

7. Rev Endocr Metab Disord. 2011 Jun;12(2):93-106.

8. Int J Womens Health. 2014 Jun 23;6:631-7.

Resources

Breast cancer screening in transgender men. (https://transcare.ucsf.edu/guidelines/breast-cancer-men).

Screening for breast cancer in transgender women. (https://transcare.ucsf.edu/guidelines/breast-cancer-women).

Transgender health and HIV (https://transcare.ucsf.edu/guidelines/hiv).

Centers for Disease Control and Prevention: HIV and Transgender People (https://www.cdc.gov/hiv/group/gender/transgender/index.html).

I recently was on a panel of experts discussing how to prevent HIV among transgender youth. Preventing HIV among transgender youth, especially transgender youth of color, remains a challenge for multiple reasons – racism, poverty, stigma, marginalization, and discrimination play a role in the HIV epidemic. A barrier to preventing HIV infections among transgender youth is a lack of knowledge on how to provide them with comprehensive sexual and reproductive health care. Here are some tips and resources that can help you ensure that transgender youth are safe and healthy.

sturti/E+

One of the challenges of obtaining a sexual history is asking the right questions to illicit the appropriate history: Focus on organs and activities instead of gender. For example, if you have a transgender male assigned female at birth, ask whether their partners produce sperm instead of asking about the sex of their partners. A transgender male’s partner may identify as female but is assigned male at birth and uses her penis during sex. Furthermore, a transgender male may be on testosterone, but he still can get pregnant. Asking how they use their organs is just as important. A transgender male who has condomless penile-vaginal sex with multiple partners is at a higher risk for HIV infection than is a transgender male who shares sex toys with his only partner.

Normalizing that you ask a comprehensive sexual history to all your patients regardless of gender identity may put the patient at ease. Many transgender people are reluctant to disclose their gender identity to their provider because they are afraid that the provider may fixate on their sexuality once they do. Stating that you ask sexual health questions to all your patients may prevent the transgender patient from feeling singled out.

Finally, you don’t have to ask a sexual history with every transgender patient, just as you wouldn’t for your cisgender patients. If a patient is complaining of a sprained ankle, a sexual history may not be helpful, compared with obtaining one when a patient comes in with pelvic pain. Many transgender patients avoid care because they are frequently asked about their sexual history or gender identity when these are not relevant to their chief complaint.

Here are some helpful questions to ask when taking a sexual history, according to the University of California, San Francisco, Transgender Care & Treatment Guidelines.¹

• Are you having sex? How many sex partners have you had in the past year?
• Who are you having sex with? What types of sex are you having? What parts of your anatomy do you use for sex?
• How do you protect yourself from STIs?
• What STIs have you had in the past, if any? When were you last tested for STIs?
• Has your partner(s) ever been diagnosed with any STIs?
• Do you use alcohol or any drugs when you have sex?
• Do you exchange sex for money, drugs, or a place to stay?

Also, use a trauma-informed approach when working with transgender patients. Many have been victims of sexual trauma. Always have a chaperone accompany you during the exam, explain to the patient what you plan to do and why it is necessary, and allow them to decline (and document their declining the physical exam). Also consider having your patient self-swab for STI screening if appropriate.¹

Like obtaining a sexual history, routine screenings for certain types of cancers will be based on the organs the patient has. For example, a transgender woman assigned male at birth will not need a cervical cancer screening, but a transgender man assigned female at birth may need one – if the patient still has a cervix. Cervical cancer screening guidelines are similar for transgender men as it is for nontransgender women, and one should use the same guidelines endorsed by the American Cancer Society, American Society of Colposcopy and Cervical Pathology, American Society of Clinical Pathologists, U.S. Preventive Services Task Force, and the World Health Organization.^2-4

Cervical screenings should never be a requirement for testosterone therapy, and no transgender male under the age of 21 years will need cervical screening. The University of California guidelines offers tips on how to make transgender men more comfortable during cervical cancer screening.⁵

Contraception and menstrual management also are important for transgender patients. Testosterone can induce amenorrhea for transgender men, but it is not good birth control. If a transgender male patient has sex with partners that produce sperm, then the physician should discuss effective birth control options. There is no ideal birth control option for transgender men. One must consider multiple factors including the patient’s desire for pregnancy, desire to cease periods, ease of administration, and risk for thrombosis.

Most transgender men may balk at the idea of taking estrogen-containing contraception, but it is more effective than oral progestin-only pills. Intrauterine devices are highly effective in pregnancy prevention and can achieve amenorrhea in 50% of users within 1 year,but some transmen may become dysphoric with the procedure. ⁶ The etonogestrel implants also are highly effective birth control, but irregular periods are common, leading to discontinuation. Depot medroxyprogesterone is highly effective in preventing pregnancy and can induce amenorrhea in 70% of users within 1 year and 80% of users in 2 years, but also is associated with weight gain in one-third of users.⁷ Finally, pubertal blockers can rapidly stop periods for transmen who are severely dysphoric from their menses; however, before achieving amenorrhea, a flare bleed can occur 4-6 weeks after administration.⁸ Support from a mental health therapist during this time is critical. Pubertal blockers, nevertheless, are not suitable birth control.

When providing affirming sexual and reproductive health care for transgender patients, key principles include focusing on organs and activities over identity. Additionally, screening for certain types of cancers also is dependent on organs. Finally, do not neglect the importance of contraception among transgender men. Taking these principles in consideration will help you provide excellent care for transgender youth.

Dr. Montano is an assistant professor of pediatrics at the University of Pittsburgh and an adolescent medicine physician at the Children’s Hospital of Pittsburgh. He said he had no relevant financial disclosures. Email him at [email protected].

References

1. Transgender people and sexually transmitted infections (https://transcare.ucsf.edu/guidelines/stis).

2. CA Cancer J Clin. 2012 May-Jun;62(3):147-72.

3. Ann Intern Med. 2012;156(12):880-91.

4. Cervical cancer screening in developing countries: Report of a WHO consultation. 2002. World Health Organization, Geneva.

5. Screening for cervical cancer for transgender men (https://transcare.ucsf.edu/guidelines/cervical-cancer).

6. Contraception. 2002 Feb;65(2):129-32.

7. Rev Endocr Metab Disord. 2011 Jun;12(2):93-106.

8. Int J Womens Health. 2014 Jun 23;6:631-7.

Resources

Breast cancer screening in transgender men. (https://transcare.ucsf.edu/guidelines/breast-cancer-men).

Screening for breast cancer in transgender women. (https://transcare.ucsf.edu/guidelines/breast-cancer-women).

Transgender health and HIV (https://transcare.ucsf.edu/guidelines/hiv).

Centers for Disease Control and Prevention: HIV and Transgender People (https://www.cdc.gov/hiv/group/gender/transgender/index.html).

Progress in reducing the number of new HIV infections has stalled, according to a Vital Signs report published by the Centers for Disease Control and Prevention based upon a simultaneous MMWR Early Release. The report indicates that many Americans with HIV are not aware of their status or are not receiving effective treatment. Furthermore, the data suggest that few Americans who could benefit from preexposure prophylaxis (PrEP), a daily pill that prevents HIV, are receiving it.

CDC Vital Signs. Dec 3, 2019

The report “shows that HIV testing, treatment, and prevention have not reached enough Americans, and it emphasizes the continued urgent need to increase these interventions,” said Jay C. Butler, MD, deputy director for infectious diseases at the CDC, at a press conference. “We made a lot of progress in the late ’90s and into the early part of the 21st century in reducing the number of new cases of HIV. But HIV prevention progress has stalled in America since 2013. This stalling underscores the need to increase resources, deploy new technologies, and build expertise, particularly in areas where they’re needed most.”

To achieve these objectives, the CDC has proposed a federal initiative called Ending the HIV Epidemic: A Plan for America. The goal of the initiative is to reduce new HIV infections by 90% by 2030, in part by expanding access to PrEP medications.

Data suggest shortcomings in diagnosis, treatment, and prevention

In its review of data on HIV testing and treatment in 2017, the Vital Signs report found that approximately 154,000 people with HIV (that is, 14% of the total population with HIV) were unaware that they had the virus. These patients consequently could not take advantage of HIV treatment to maintain health, control the virus, and prevent HIV transmission. Young people aged 13-24 years were less likely to know their HIV status than did those aged 25 years and older, according to the report.

Furthermore, approximately two-thirds (63%) of patients who knew that they had HIV had the virus under control through effective treatment. Young people and African Americans were least likely to have the virus under control, according to the report.

The report also examines data about treatment with PrEP in 2018. About 1.2 million Americans could benefit from PrEP, but only 219,700 (18%) of them had received a prescription for the drug. The eligible groups with the lowest rates of coverage were young people, African Americans, and Latinos.

The report presents a conservative estimate of PrEP coverage, however. Researchers examined data from 92% of prescriptions from retail pharmacies in the United States but did not include prescriptions from closed health care systems such as managed care organizations and military health plans. PrEP coverage in 2018 likely was higher than these estimates indicate, according to the CDC.

“There has been a rapid increase in the number of people taking PrEP over the past 3 years, but there is no doubt that PrEP uptake is too low,” said Eugene McCray, MD, director of CDC’s division of HIV/AIDS prevention. “We are working hard to increase access to PrEP, especially among gay and bisexual men, women, transgender people, young people, African Americans, and Latinos.”

The rate of new HIV infections has not decreased, but remained stable, according to the report. The CDC estimates that there were about 38,000 new infections per year from 2013 to 2017.

Proposed initiative focuses on areas of greatest need

The proposed Ending the HIV Epidemic initiative, if it is funded, will target the locations of greatest need throughout the country. Its initial focus will be on 50 areas that account for more than half of new HIV diagnoses, including 48 counties; San Juan, Puerto Rico; and Washington, D.C. It also will direct resources to seven states with high rates of infection in rural areas. In a second phase, the initiative will expand nationwide, provided that additional resources are made available.

The proposed initiative relies on four science-based strategies. First, it will aim to diagnose all Americans with HIV (at least 95% of HIV infections) as early as possible. Second, the initiative will enable people with HIV to receive treatment rapidly and effectively. The CDC’s target is to achieve viral suppression in at least 95% of people with diagnosed HIV. Third, the initiative will use proven interventions such as PrEP and syringe services programs to prevent new HIV transmissions. One related goal is for at least 50% of people who could benefit from PrEP to receive a prescription. Finally, the initiative is intended to respond quickly to potential HIV outbreaks and provide prevention and treatment to those who need them.

The U.S. Department of Health & Human Services already has taken steps to enable the initiative to be implemented quickly if it is funded in 2020. The department has provided funding to Baltimore City, Md.; DeKalb County, Ga.; and East Baton Rouge Parish, La. to begin pursuing parts of the initiative. These communities are encouraged to share the lessons of their experiences with other communities. HHS also has supported local efforts to develop plans under the initiative in all priority geographic areas. These plans draw upon recommendations from the community, HIV-planning bodies, and health care providers.

“Ending the HIV epidemic would be one of the greatest public health triumphs in our nation’s history,” said Dr. McCray.

[email protected]

SOURCES: Centers for Disease Control and Prevention. CDC Vital Signs. 2019 Dec 3. and Harris NS et al. MMWR Morb Mortal Wkly Rep. 2019 Dec 3.

Progress in reducing the number of new HIV infections has stalled, according to a Vital Signs report published by the Centers for Disease Control and Prevention based upon a simultaneous MMWR Early Release. The report indicates that many Americans with HIV are not aware of their status or are not receiving effective treatment. Furthermore, the data suggest that few Americans who could benefit from preexposure prophylaxis (PrEP), a daily pill that prevents HIV, are receiving it.

CDC Vital Signs. Dec 3, 2019

The report “shows that HIV testing, treatment, and prevention have not reached enough Americans, and it emphasizes the continued urgent need to increase these interventions,” said Jay C. Butler, MD, deputy director for infectious diseases at the CDC, at a press conference. “We made a lot of progress in the late ’90s and into the early part of the 21st century in reducing the number of new cases of HIV. But HIV prevention progress has stalled in America since 2013. This stalling underscores the need to increase resources, deploy new technologies, and build expertise, particularly in areas where they’re needed most.”

To achieve these objectives, the CDC has proposed a federal initiative called Ending the HIV Epidemic: A Plan for America. The goal of the initiative is to reduce new HIV infections by 90% by 2030, in part by expanding access to PrEP medications.

Data suggest shortcomings in diagnosis, treatment, and prevention

In its review of data on HIV testing and treatment in 2017, the Vital Signs report found that approximately 154,000 people with HIV (that is, 14% of the total population with HIV) were unaware that they had the virus. These patients consequently could not take advantage of HIV treatment to maintain health, control the virus, and prevent HIV transmission. Young people aged 13-24 years were less likely to know their HIV status than did those aged 25 years and older, according to the report.

Furthermore, approximately two-thirds (63%) of patients who knew that they had HIV had the virus under control through effective treatment. Young people and African Americans were least likely to have the virus under control, according to the report.

The report also examines data about treatment with PrEP in 2018. About 1.2 million Americans could benefit from PrEP, but only 219,700 (18%) of them had received a prescription for the drug. The eligible groups with the lowest rates of coverage were young people, African Americans, and Latinos.

The report presents a conservative estimate of PrEP coverage, however. Researchers examined data from 92% of prescriptions from retail pharmacies in the United States but did not include prescriptions from closed health care systems such as managed care organizations and military health plans. PrEP coverage in 2018 likely was higher than these estimates indicate, according to the CDC.

“There has been a rapid increase in the number of people taking PrEP over the past 3 years, but there is no doubt that PrEP uptake is too low,” said Eugene McCray, MD, director of CDC’s division of HIV/AIDS prevention. “We are working hard to increase access to PrEP, especially among gay and bisexual men, women, transgender people, young people, African Americans, and Latinos.”

The rate of new HIV infections has not decreased, but remained stable, according to the report. The CDC estimates that there were about 38,000 new infections per year from 2013 to 2017.

Proposed initiative focuses on areas of greatest need

The proposed Ending the HIV Epidemic initiative, if it is funded, will target the locations of greatest need throughout the country. Its initial focus will be on 50 areas that account for more than half of new HIV diagnoses, including 48 counties; San Juan, Puerto Rico; and Washington, D.C. It also will direct resources to seven states with high rates of infection in rural areas. In a second phase, the initiative will expand nationwide, provided that additional resources are made available.

The proposed initiative relies on four science-based strategies. First, it will aim to diagnose all Americans with HIV (at least 95% of HIV infections) as early as possible. Second, the initiative will enable people with HIV to receive treatment rapidly and effectively. The CDC’s target is to achieve viral suppression in at least 95% of people with diagnosed HIV. Third, the initiative will use proven interventions such as PrEP and syringe services programs to prevent new HIV transmissions. One related goal is for at least 50% of people who could benefit from PrEP to receive a prescription. Finally, the initiative is intended to respond quickly to potential HIV outbreaks and provide prevention and treatment to those who need them.

The U.S. Department of Health & Human Services already has taken steps to enable the initiative to be implemented quickly if it is funded in 2020. The department has provided funding to Baltimore City, Md.; DeKalb County, Ga.; and East Baton Rouge Parish, La. to begin pursuing parts of the initiative. These communities are encouraged to share the lessons of their experiences with other communities. HHS also has supported local efforts to develop plans under the initiative in all priority geographic areas. These plans draw upon recommendations from the community, HIV-planning bodies, and health care providers.

“Ending the HIV epidemic would be one of the greatest public health triumphs in our nation’s history,” said Dr. McCray.

[email protected]

SOURCES: Centers for Disease Control and Prevention. CDC Vital Signs. 2019 Dec 3. and Harris NS et al. MMWR Morb Mortal Wkly Rep. 2019 Dec 3.

Progress in reducing the number of new HIV infections has stalled, according to a Vital Signs report published by the Centers for Disease Control and Prevention based upon a simultaneous MMWR Early Release. The report indicates that many Americans with HIV are not aware of their status or are not receiving effective treatment. Furthermore, the data suggest that few Americans who could benefit from preexposure prophylaxis (PrEP), a daily pill that prevents HIV, are receiving it.

CDC Vital Signs. Dec 3, 2019

The report “shows that HIV testing, treatment, and prevention have not reached enough Americans, and it emphasizes the continued urgent need to increase these interventions,” said Jay C. Butler, MD, deputy director for infectious diseases at the CDC, at a press conference. “We made a lot of progress in the late ’90s and into the early part of the 21st century in reducing the number of new cases of HIV. But HIV prevention progress has stalled in America since 2013. This stalling underscores the need to increase resources, deploy new technologies, and build expertise, particularly in areas where they’re needed most.”

To achieve these objectives, the CDC has proposed a federal initiative called Ending the HIV Epidemic: A Plan for America. The goal of the initiative is to reduce new HIV infections by 90% by 2030, in part by expanding access to PrEP medications.

Data suggest shortcomings in diagnosis, treatment, and prevention

In its review of data on HIV testing and treatment in 2017, the Vital Signs report found that approximately 154,000 people with HIV (that is, 14% of the total population with HIV) were unaware that they had the virus. These patients consequently could not take advantage of HIV treatment to maintain health, control the virus, and prevent HIV transmission. Young people aged 13-24 years were less likely to know their HIV status than did those aged 25 years and older, according to the report.

Furthermore, approximately two-thirds (63%) of patients who knew that they had HIV had the virus under control through effective treatment. Young people and African Americans were least likely to have the virus under control, according to the report.

The report also examines data about treatment with PrEP in 2018. About 1.2 million Americans could benefit from PrEP, but only 219,700 (18%) of them had received a prescription for the drug. The eligible groups with the lowest rates of coverage were young people, African Americans, and Latinos.

The report presents a conservative estimate of PrEP coverage, however. Researchers examined data from 92% of prescriptions from retail pharmacies in the United States but did not include prescriptions from closed health care systems such as managed care organizations and military health plans. PrEP coverage in 2018 likely was higher than these estimates indicate, according to the CDC.

“There has been a rapid increase in the number of people taking PrEP over the past 3 years, but there is no doubt that PrEP uptake is too low,” said Eugene McCray, MD, director of CDC’s division of HIV/AIDS prevention. “We are working hard to increase access to PrEP, especially among gay and bisexual men, women, transgender people, young people, African Americans, and Latinos.”

The rate of new HIV infections has not decreased, but remained stable, according to the report. The CDC estimates that there were about 38,000 new infections per year from 2013 to 2017.

Proposed initiative focuses on areas of greatest need

The proposed Ending the HIV Epidemic initiative, if it is funded, will target the locations of greatest need throughout the country. Its initial focus will be on 50 areas that account for more than half of new HIV diagnoses, including 48 counties; San Juan, Puerto Rico; and Washington, D.C. It also will direct resources to seven states with high rates of infection in rural areas. In a second phase, the initiative will expand nationwide, provided that additional resources are made available.

The proposed initiative relies on four science-based strategies. First, it will aim to diagnose all Americans with HIV (at least 95% of HIV infections) as early as possible. Second, the initiative will enable people with HIV to receive treatment rapidly and effectively. The CDC’s target is to achieve viral suppression in at least 95% of people with diagnosed HIV. Third, the initiative will use proven interventions such as PrEP and syringe services programs to prevent new HIV transmissions. One related goal is for at least 50% of people who could benefit from PrEP to receive a prescription. Finally, the initiative is intended to respond quickly to potential HIV outbreaks and provide prevention and treatment to those who need them.

The U.S. Department of Health & Human Services already has taken steps to enable the initiative to be implemented quickly if it is funded in 2020. The department has provided funding to Baltimore City, Md.; DeKalb County, Ga.; and East Baton Rouge Parish, La. to begin pursuing parts of the initiative. These communities are encouraged to share the lessons of their experiences with other communities. HHS also has supported local efforts to develop plans under the initiative in all priority geographic areas. These plans draw upon recommendations from the community, HIV-planning bodies, and health care providers.

“Ending the HIV epidemic would be one of the greatest public health triumphs in our nation’s history,” said Dr. McCray.

[email protected]

SOURCES: Centers for Disease Control and Prevention. CDC Vital Signs. 2019 Dec 3. and Harris NS et al. MMWR Morb Mortal Wkly Rep. 2019 Dec 3.

Initiating antiretroviral therapy within an hour after birth, rather than waiting a few weeks, lowers the reservoir of HIV virus and improves immune response, early results from an ongoing study in Botswana, Africa, showed.

Comstock/Thinkstock

Despite advances in treatment programs during pregnancy that prevent mother to child HIV transmission, 300-500 pediatric HIV infections occur each day in sub-Saharan Africa, Roger Shapiro, MD, MPH, said during a media teleconference organized by the American Association for the Advancement of Science. “Most pediatric HIV diagnosis programs currently test children at 4-6 weeks of age to identify infections that occur either in pregnancy or during delivery,” said Dr. Shapiro, associate professor of immunology and infectious diseases at the Harvard T.H. Chan School of Public Health, Boston. “However, these programs miss the opportunity to begin immediate antiretroviral treatment for children who can be identified earlier. There are benefits to starting treatment and arresting HIV replication in the first week of life. These include limiting the viral reservoir or the population of infected cells, limiting potentially harmful immune responses to the virus, and preventing the rapid decline in health that can occur in the early weeks of HIV infection in infants. Without treatment, 50% of HIV-infected children regress to death by 2 years. Starting treatment in the first weeks or months of life has been shown to improve survival.”

With these benefits in mind, he and his associates initiated the Early Infant Treatment (EIT) study in 2015 to diagnose and treat HIV infected infants in Botswana in the first week of life or as early as possible after infection. They screened more than 10,000 children and identified 40 that were HIV infected. “This low transmission rate is a testament to the fact that most HIV-positive women in Botswana receive three-drug treatment in pregnancy, which is highly successful in blocking transmission,” Dr. Shapiro said. “When we identified an HIV-infected infant, we consented mothers to allow us to start treatment right away. We used a series of regimens because there are limited options. The available options include older drugs, some of which are no longer used for adults but which were the only options for children.”

The researchers initiated three initial drugs approved for newborns: nevirapine, zidovudine, and lamivudine, and then changed the regimen slightly after a few weeks, when they used ritonavir-boosted lopinavir, plus the lamivudine and zidovudine. “We followed the children weekly at first, then at monthly refill visits, and kept close track of how they were taking the medicines and the level of virus in each child’s blood,” Dr. Shapiro said.

In a manuscript published online in Science Translational Medicine on Nov. 27, 2019, he and his associates reported results of the first 10 children enrolled in the EIT study who reached about 96 weeks on treatment. For comparison, they also enrolled a group of children as controls, who started treatment later in the first year of life, after being identified at a more standard time of 4-6 weeks. Tests performed included droplet digital polymerase chain reaction, HIV near-full-genome sequencing, whole-genome amplification, and flow cytometry.

“What we wanted to focus on are the HIV reservoir cells that are persisting in the setting of antiretroviral treatment,” study coauthor Mathias Lichterfeld, MD, PhD, explained during the teleconference. “Those are the cells that would cause viral rebound if treatment were to be interrupted. We used complex technology to look at these cells, using next-generation sequencing, which allows us to identify those cells that harbor HIV that has the ability to initiate new viral replication.”

He and his colleagues observed that the number of reservoir cells was significantly smaller than in adults who were on ART for a median of 16 years. It also was smaller than in infected infants who started ART treatment weeks after birth.

In addition, immune activation was reduced in the cohort of infants who were treated immediately after birth.

“We are seeing a distinct advantage of early treatment initiation,” said Dr. Lichterfeld of the infectious disease division at Brigham and Women’s Hospital, Boston. “By doing these assays we see both virological benefits in terms of a very-low reservoir size, and we see immune system characteristics that are also associated with better abilities for antimicrobial immune defense and a lower level of immune activation.”

Another study coauthor, Daniel R. Kuritzkes, MD, chief of the infectious disease division at Brigham and Women’s Hospital, said the findings show “how critically important” it is to extend studies of HIV cure or long-term remission to infants and children. “Very-early intervention in neonates limits the size of the reservoir and offers us the best opportunity for future interventions aimed at cure and long-term drug-free remission of HIV infection,” he said. “We don’t think the current intervention is itself curative, but it sets the stage for the capacity to offer additional innovative interventions in the future. Beyond the importance of this work for cure research per se, this very early intervention in neonates also has the potential of conferring important clinical benefits to the children who participated in this study. Finally, our study demonstrates the feasibility and importance of doing this type of research in neonates in resource-limited settings, given the appropriate infrastructure.”

EIT is supported by the National Institutes of Health. Dr. Lichterfeld disclosed having received speaking and consulting honoraria from Merck and Gilead. Dr. Kuritzkes disclosed having received consulting honoraria and/or research support from Gilead, Merck, and ViiV.

[email protected]

SOURCE: Garcia-Broncano P et al. Sci Transl Med. 2019 Nov 27. eaax7350.

Initiating antiretroviral therapy within an hour after birth, rather than waiting a few weeks, lowers the reservoir of HIV virus and improves immune response, early results from an ongoing study in Botswana, Africa, showed.

Comstock/Thinkstock

Despite advances in treatment programs during pregnancy that prevent mother to child HIV transmission, 300-500 pediatric HIV infections occur each day in sub-Saharan Africa, Roger Shapiro, MD, MPH, said during a media teleconference organized by the American Association for the Advancement of Science. “Most pediatric HIV diagnosis programs currently test children at 4-6 weeks of age to identify infections that occur either in pregnancy or during delivery,” said Dr. Shapiro, associate professor of immunology and infectious diseases at the Harvard T.H. Chan School of Public Health, Boston. “However, these programs miss the opportunity to begin immediate antiretroviral treatment for children who can be identified earlier. There are benefits to starting treatment and arresting HIV replication in the first week of life. These include limiting the viral reservoir or the population of infected cells, limiting potentially harmful immune responses to the virus, and preventing the rapid decline in health that can occur in the early weeks of HIV infection in infants. Without treatment, 50% of HIV-infected children regress to death by 2 years. Starting treatment in the first weeks or months of life has been shown to improve survival.”

With these benefits in mind, he and his associates initiated the Early Infant Treatment (EIT) study in 2015 to diagnose and treat HIV infected infants in Botswana in the first week of life or as early as possible after infection. They screened more than 10,000 children and identified 40 that were HIV infected. “This low transmission rate is a testament to the fact that most HIV-positive women in Botswana receive three-drug treatment in pregnancy, which is highly successful in blocking transmission,” Dr. Shapiro said. “When we identified an HIV-infected infant, we consented mothers to allow us to start treatment right away. We used a series of regimens because there are limited options. The available options include older drugs, some of which are no longer used for adults but which were the only options for children.”

The researchers initiated three initial drugs approved for newborns: nevirapine, zidovudine, and lamivudine, and then changed the regimen slightly after a few weeks, when they used ritonavir-boosted lopinavir, plus the lamivudine and zidovudine. “We followed the children weekly at first, then at monthly refill visits, and kept close track of how they were taking the medicines and the level of virus in each child’s blood,” Dr. Shapiro said.

In a manuscript published online in Science Translational Medicine on Nov. 27, 2019, he and his associates reported results of the first 10 children enrolled in the EIT study who reached about 96 weeks on treatment. For comparison, they also enrolled a group of children as controls, who started treatment later in the first year of life, after being identified at a more standard time of 4-6 weeks. Tests performed included droplet digital polymerase chain reaction, HIV near-full-genome sequencing, whole-genome amplification, and flow cytometry.

“What we wanted to focus on are the HIV reservoir cells that are persisting in the setting of antiretroviral treatment,” study coauthor Mathias Lichterfeld, MD, PhD, explained during the teleconference. “Those are the cells that would cause viral rebound if treatment were to be interrupted. We used complex technology to look at these cells, using next-generation sequencing, which allows us to identify those cells that harbor HIV that has the ability to initiate new viral replication.”

He and his colleagues observed that the number of reservoir cells was significantly smaller than in adults who were on ART for a median of 16 years. It also was smaller than in infected infants who started ART treatment weeks after birth.

In addition, immune activation was reduced in the cohort of infants who were treated immediately after birth.

“We are seeing a distinct advantage of early treatment initiation,” said Dr. Lichterfeld of the infectious disease division at Brigham and Women’s Hospital, Boston. “By doing these assays we see both virological benefits in terms of a very-low reservoir size, and we see immune system characteristics that are also associated with better abilities for antimicrobial immune defense and a lower level of immune activation.”

Another study coauthor, Daniel R. Kuritzkes, MD, chief of the infectious disease division at Brigham and Women’s Hospital, said the findings show “how critically important” it is to extend studies of HIV cure or long-term remission to infants and children. “Very-early intervention in neonates limits the size of the reservoir and offers us the best opportunity for future interventions aimed at cure and long-term drug-free remission of HIV infection,” he said. “We don’t think the current intervention is itself curative, but it sets the stage for the capacity to offer additional innovative interventions in the future. Beyond the importance of this work for cure research per se, this very early intervention in neonates also has the potential of conferring important clinical benefits to the children who participated in this study. Finally, our study demonstrates the feasibility and importance of doing this type of research in neonates in resource-limited settings, given the appropriate infrastructure.”

EIT is supported by the National Institutes of Health. Dr. Lichterfeld disclosed having received speaking and consulting honoraria from Merck and Gilead. Dr. Kuritzkes disclosed having received consulting honoraria and/or research support from Gilead, Merck, and ViiV.

[email protected]

SOURCE: Garcia-Broncano P et al. Sci Transl Med. 2019 Nov 27. eaax7350.

Initiating antiretroviral therapy within an hour after birth, rather than waiting a few weeks, lowers the reservoir of HIV virus and improves immune response, early results from an ongoing study in Botswana, Africa, showed.

Comstock/Thinkstock

Despite advances in treatment programs during pregnancy that prevent mother to child HIV transmission, 300-500 pediatric HIV infections occur each day in sub-Saharan Africa, Roger Shapiro, MD, MPH, said during a media teleconference organized by the American Association for the Advancement of Science. “Most pediatric HIV diagnosis programs currently test children at 4-6 weeks of age to identify infections that occur either in pregnancy or during delivery,” said Dr. Shapiro, associate professor of immunology and infectious diseases at the Harvard T.H. Chan School of Public Health, Boston. “However, these programs miss the opportunity to begin immediate antiretroviral treatment for children who can be identified earlier. There are benefits to starting treatment and arresting HIV replication in the first week of life. These include limiting the viral reservoir or the population of infected cells, limiting potentially harmful immune responses to the virus, and preventing the rapid decline in health that can occur in the early weeks of HIV infection in infants. Without treatment, 50% of HIV-infected children regress to death by 2 years. Starting treatment in the first weeks or months of life has been shown to improve survival.”

With these benefits in mind, he and his associates initiated the Early Infant Treatment (EIT) study in 2015 to diagnose and treat HIV infected infants in Botswana in the first week of life or as early as possible after infection. They screened more than 10,000 children and identified 40 that were HIV infected. “This low transmission rate is a testament to the fact that most HIV-positive women in Botswana receive three-drug treatment in pregnancy, which is highly successful in blocking transmission,” Dr. Shapiro said. “When we identified an HIV-infected infant, we consented mothers to allow us to start treatment right away. We used a series of regimens because there are limited options. The available options include older drugs, some of which are no longer used for adults but which were the only options for children.”

The researchers initiated three initial drugs approved for newborns: nevirapine, zidovudine, and lamivudine, and then changed the regimen slightly after a few weeks, when they used ritonavir-boosted lopinavir, plus the lamivudine and zidovudine. “We followed the children weekly at first, then at monthly refill visits, and kept close track of how they were taking the medicines and the level of virus in each child’s blood,” Dr. Shapiro said.

In a manuscript published online in Science Translational Medicine on Nov. 27, 2019, he and his associates reported results of the first 10 children enrolled in the EIT study who reached about 96 weeks on treatment. For comparison, they also enrolled a group of children as controls, who started treatment later in the first year of life, after being identified at a more standard time of 4-6 weeks. Tests performed included droplet digital polymerase chain reaction, HIV near-full-genome sequencing, whole-genome amplification, and flow cytometry.

“What we wanted to focus on are the HIV reservoir cells that are persisting in the setting of antiretroviral treatment,” study coauthor Mathias Lichterfeld, MD, PhD, explained during the teleconference. “Those are the cells that would cause viral rebound if treatment were to be interrupted. We used complex technology to look at these cells, using next-generation sequencing, which allows us to identify those cells that harbor HIV that has the ability to initiate new viral replication.”

He and his colleagues observed that the number of reservoir cells was significantly smaller than in adults who were on ART for a median of 16 years. It also was smaller than in infected infants who started ART treatment weeks after birth.

In addition, immune activation was reduced in the cohort of infants who were treated immediately after birth.

“We are seeing a distinct advantage of early treatment initiation,” said Dr. Lichterfeld of the infectious disease division at Brigham and Women’s Hospital, Boston. “By doing these assays we see both virological benefits in terms of a very-low reservoir size, and we see immune system characteristics that are also associated with better abilities for antimicrobial immune defense and a lower level of immune activation.”

Another study coauthor, Daniel R. Kuritzkes, MD, chief of the infectious disease division at Brigham and Women’s Hospital, said the findings show “how critically important” it is to extend studies of HIV cure or long-term remission to infants and children. “Very-early intervention in neonates limits the size of the reservoir and offers us the best opportunity for future interventions aimed at cure and long-term drug-free remission of HIV infection,” he said. “We don’t think the current intervention is itself curative, but it sets the stage for the capacity to offer additional innovative interventions in the future. Beyond the importance of this work for cure research per se, this very early intervention in neonates also has the potential of conferring important clinical benefits to the children who participated in this study. Finally, our study demonstrates the feasibility and importance of doing this type of research in neonates in resource-limited settings, given the appropriate infrastructure.”

EIT is supported by the National Institutes of Health. Dr. Lichterfeld disclosed having received speaking and consulting honoraria from Merck and Gilead. Dr. Kuritzkes disclosed having received consulting honoraria and/or research support from Gilead, Merck, and ViiV.

[email protected]

SOURCE: Garcia-Broncano P et al. Sci Transl Med. 2019 Nov 27. eaax7350.

A new study has found that distributing HIV self-tests to at-risk groups such as men who have sex with men can increase testing frequency and uncover more previously undiagnosed infections.

“Based on these findings, HIV prevention programs might consider adding an HIV self-testing mail distribution component to their portfolio of HIV prevention services for high-risk populations,” wrote Robin J. MacGowan, MPH, of the Centers for Disease Control and Prevention and coauthors. The study was published in JAMA Internal Medicine.

To assess the potential benefits of expanded HIV self-testing, the CDC sponsored a 12-month randomized clinical trial called the Evaluation of Rapid HIV Self-testing Among MSM Project (eSTAMP). Participants were recruited via social media, music and dating websites; criteria included being aged at least 18 years, never having tested positive for HIV, and having engaged in anal sex with at least one man in the past year. The 2,665 participants were assigned to either the self-testing (ST) group (n = 1,325) or the control group (n = 1,340); the ST group received four self-tests in the mail with the option for more each quarter. All participants were asked to complete follow-up surveys every 3 months.

Of all participants, 1,991 (74.7%) initiated at least one follow-up survey. Participants in the ST group reported testing more frequently than those in the control group (an average of 5.3 tests vs. 1.5 tests; P less than .001). In addition, a much higher percentage of ST participants tested at least three times in 12 months (777 of 1014 [76.6%]), compared with controls (215 of 977 [22.0%]). A total of 36 participants tested newly positive for HIV during the study; over the first 3 months, 12 of the 14 infections were identified in the ST group (P less than .007). Over 12 months, 25 of the infections came from the ST group, compared with 11 in the control group (P = .02).

When HIV tests are free and convenient, members of high-risk populations will use them, wrote Julia M. Janssen, MD, of the University of California, San Francisco, and Mitchell H. Katz, MD, of New York City Health and Hospitals in an accompanying editorial (JAMA Intern Med. 2019 Nov 18. doi: 10.1001/jamainternmed.2019.5442). But tests are not enough; the authors noted the role of primary care physicians in prescribing pre-exposure prophylaxis (PrEP) for at-risk patients as key in decreasing rates of new HIV diagnoses.

“The self-testing kits targeting individuals at high risk of acquiring HIV complement the use of PrEP,” they added, “and are another way to accelerate the end of the epidemic.”

The study was funded by the CDC. One author reported receiving grants and fees from the CDC and the National Institutes of Health, along with personal fees from Elsevier and the Ontario HIV Treatment Network. Dr. Katz reported receiving royalties for a chapter on HIV in Lange’s Current Medicine and Diagnostic Testing.

SOURCE: MacGowan RJ et al. JAMA Intern Med. 2019 Nov 18. doi: 10.1001/jamainternmed.2019.5222.

A new study has found that distributing HIV self-tests to at-risk groups such as men who have sex with men can increase testing frequency and uncover more previously undiagnosed infections.

“Based on these findings, HIV prevention programs might consider adding an HIV self-testing mail distribution component to their portfolio of HIV prevention services for high-risk populations,” wrote Robin J. MacGowan, MPH, of the Centers for Disease Control and Prevention and coauthors. The study was published in JAMA Internal Medicine.

To assess the potential benefits of expanded HIV self-testing, the CDC sponsored a 12-month randomized clinical trial called the Evaluation of Rapid HIV Self-testing Among MSM Project (eSTAMP). Participants were recruited via social media, music and dating websites; criteria included being aged at least 18 years, never having tested positive for HIV, and having engaged in anal sex with at least one man in the past year. The 2,665 participants were assigned to either the self-testing (ST) group (n = 1,325) or the control group (n = 1,340); the ST group received four self-tests in the mail with the option for more each quarter. All participants were asked to complete follow-up surveys every 3 months.

Of all participants, 1,991 (74.7%) initiated at least one follow-up survey. Participants in the ST group reported testing more frequently than those in the control group (an average of 5.3 tests vs. 1.5 tests; P less than .001). In addition, a much higher percentage of ST participants tested at least three times in 12 months (777 of 1014 [76.6%]), compared with controls (215 of 977 [22.0%]). A total of 36 participants tested newly positive for HIV during the study; over the first 3 months, 12 of the 14 infections were identified in the ST group (P less than .007). Over 12 months, 25 of the infections came from the ST group, compared with 11 in the control group (P = .02).

When HIV tests are free and convenient, members of high-risk populations will use them, wrote Julia M. Janssen, MD, of the University of California, San Francisco, and Mitchell H. Katz, MD, of New York City Health and Hospitals in an accompanying editorial (JAMA Intern Med. 2019 Nov 18. doi: 10.1001/jamainternmed.2019.5442). But tests are not enough; the authors noted the role of primary care physicians in prescribing pre-exposure prophylaxis (PrEP) for at-risk patients as key in decreasing rates of new HIV diagnoses.

“The self-testing kits targeting individuals at high risk of acquiring HIV complement the use of PrEP,” they added, “and are another way to accelerate the end of the epidemic.”

The study was funded by the CDC. One author reported receiving grants and fees from the CDC and the National Institutes of Health, along with personal fees from Elsevier and the Ontario HIV Treatment Network. Dr. Katz reported receiving royalties for a chapter on HIV in Lange’s Current Medicine and Diagnostic Testing.

SOURCE: MacGowan RJ et al. JAMA Intern Med. 2019 Nov 18. doi: 10.1001/jamainternmed.2019.5222.

A new study has found that distributing HIV self-tests to at-risk groups such as men who have sex with men can increase testing frequency and uncover more previously undiagnosed infections.

“Based on these findings, HIV prevention programs might consider adding an HIV self-testing mail distribution component to their portfolio of HIV prevention services for high-risk populations,” wrote Robin J. MacGowan, MPH, of the Centers for Disease Control and Prevention and coauthors. The study was published in JAMA Internal Medicine.

To assess the potential benefits of expanded HIV self-testing, the CDC sponsored a 12-month randomized clinical trial called the Evaluation of Rapid HIV Self-testing Among MSM Project (eSTAMP). Participants were recruited via social media, music and dating websites; criteria included being aged at least 18 years, never having tested positive for HIV, and having engaged in anal sex with at least one man in the past year. The 2,665 participants were assigned to either the self-testing (ST) group (n = 1,325) or the control group (n = 1,340); the ST group received four self-tests in the mail with the option for more each quarter. All participants were asked to complete follow-up surveys every 3 months.

Of all participants, 1,991 (74.7%) initiated at least one follow-up survey. Participants in the ST group reported testing more frequently than those in the control group (an average of 5.3 tests vs. 1.5 tests; P less than .001). In addition, a much higher percentage of ST participants tested at least three times in 12 months (777 of 1014 [76.6%]), compared with controls (215 of 977 [22.0%]). A total of 36 participants tested newly positive for HIV during the study; over the first 3 months, 12 of the 14 infections were identified in the ST group (P less than .007). Over 12 months, 25 of the infections came from the ST group, compared with 11 in the control group (P = .02).

When HIV tests are free and convenient, members of high-risk populations will use them, wrote Julia M. Janssen, MD, of the University of California, San Francisco, and Mitchell H. Katz, MD, of New York City Health and Hospitals in an accompanying editorial (JAMA Intern Med. 2019 Nov 18. doi: 10.1001/jamainternmed.2019.5442). But tests are not enough; the authors noted the role of primary care physicians in prescribing pre-exposure prophylaxis (PrEP) for at-risk patients as key in decreasing rates of new HIV diagnoses.

“The self-testing kits targeting individuals at high risk of acquiring HIV complement the use of PrEP,” they added, “and are another way to accelerate the end of the epidemic.”

The study was funded by the CDC. One author reported receiving grants and fees from the CDC and the National Institutes of Health, along with personal fees from Elsevier and the Ontario HIV Treatment Network. Dr. Katz reported receiving royalties for a chapter on HIV in Lange’s Current Medicine and Diagnostic Testing.

SOURCE: MacGowan RJ et al. JAMA Intern Med. 2019 Nov 18. doi: 10.1001/jamainternmed.2019.5222.

Hepatitis C virus testing should be combined with HIV integrated care services among people who inject drugs (PWID), according to researchers reporting on a multisite randomized trial of nearly 12,000 HIV-infected individuals in India.

Courtesy NIH

HCV antibody prevalence at these sites ranged from 7.2%-76.6%. Across six integrated care centers (ICCs), 5,263 clients underwent HCV testing, of whom 2,278 were newly diagnosed. At evaluation, PWID in ICC clusters were nearly four times more likely to report being tested for HCV than those in usual care clusters (adjusted prevalence ratio [aPR]: 3.69), according to the report by Sunil Suhas Solomon, MD, of Johns Hopkins University School of Medicine, Baltimore, and colleagues.

PWID in ICC clusters were also seven times more likely to be aware of their HCV status (aPR: 7.11; 95% confidence interval: 1.14, 44.3) and significantly more likely to initiate treatment, (aPR: 9.86; 95% CI: 1.52, 63.8), than individuals in usual care, the authors stated in their report published online ahead of press in the Journal of Hepatology.

“These data provide among the first empirical support of the benefits of integrating HCV testing with HIV prevention and treatment services for PWID. Over a short duration, we observed significant impact on community-level HCV testing and awareness of HCV status among PWID. While additional strategies might be required to improve population awareness levels, integration of HCV testing with HIV programs for PWID particularly given the high burden of HIV/HCV coinfection represents a critical first step,” the researchers concluded.

The study was funded by the National Institutes of Health and the Elton John AIDS Foundation. The authors reported that they had no relevant disclosures.

[email protected]

SOURCE: Solomon, SS et al. J Hepatol. 2019. doi.org/10.1016/j.jhep.2019.09.022.

Hepatitis C virus testing should be combined with HIV integrated care services among people who inject drugs (PWID), according to researchers reporting on a multisite randomized trial of nearly 12,000 HIV-infected individuals in India.

Courtesy NIH

HCV antibody prevalence at these sites ranged from 7.2%-76.6%. Across six integrated care centers (ICCs), 5,263 clients underwent HCV testing, of whom 2,278 were newly diagnosed. At evaluation, PWID in ICC clusters were nearly four times more likely to report being tested for HCV than those in usual care clusters (adjusted prevalence ratio [aPR]: 3.69), according to the report by Sunil Suhas Solomon, MD, of Johns Hopkins University School of Medicine, Baltimore, and colleagues.

PWID in ICC clusters were also seven times more likely to be aware of their HCV status (aPR: 7.11; 95% confidence interval: 1.14, 44.3) and significantly more likely to initiate treatment, (aPR: 9.86; 95% CI: 1.52, 63.8), than individuals in usual care, the authors stated in their report published online ahead of press in the Journal of Hepatology.

“These data provide among the first empirical support of the benefits of integrating HCV testing with HIV prevention and treatment services for PWID. Over a short duration, we observed significant impact on community-level HCV testing and awareness of HCV status among PWID. While additional strategies might be required to improve population awareness levels, integration of HCV testing with HIV programs for PWID particularly given the high burden of HIV/HCV coinfection represents a critical first step,” the researchers concluded.

The study was funded by the National Institutes of Health and the Elton John AIDS Foundation. The authors reported that they had no relevant disclosures.

[email protected]

SOURCE: Solomon, SS et al. J Hepatol. 2019. doi.org/10.1016/j.jhep.2019.09.022.

Hepatitis C virus testing should be combined with HIV integrated care services among people who inject drugs (PWID), according to researchers reporting on a multisite randomized trial of nearly 12,000 HIV-infected individuals in India.

Courtesy NIH

HCV antibody prevalence at these sites ranged from 7.2%-76.6%. Across six integrated care centers (ICCs), 5,263 clients underwent HCV testing, of whom 2,278 were newly diagnosed. At evaluation, PWID in ICC clusters were nearly four times more likely to report being tested for HCV than those in usual care clusters (adjusted prevalence ratio [aPR]: 3.69), according to the report by Sunil Suhas Solomon, MD, of Johns Hopkins University School of Medicine, Baltimore, and colleagues.

PWID in ICC clusters were also seven times more likely to be aware of their HCV status (aPR: 7.11; 95% confidence interval: 1.14, 44.3) and significantly more likely to initiate treatment, (aPR: 9.86; 95% CI: 1.52, 63.8), than individuals in usual care, the authors stated in their report published online ahead of press in the Journal of Hepatology.

“These data provide among the first empirical support of the benefits of integrating HCV testing with HIV prevention and treatment services for PWID. Over a short duration, we observed significant impact on community-level HCV testing and awareness of HCV status among PWID. While additional strategies might be required to improve population awareness levels, integration of HCV testing with HIV programs for PWID particularly given the high burden of HIV/HCV coinfection represents a critical first step,” the researchers concluded.

The study was funded by the National Institutes of Health and the Elton John AIDS Foundation. The authors reported that they had no relevant disclosures.

[email protected]

SOURCE: Solomon, SS et al. J Hepatol. 2019. doi.org/10.1016/j.jhep.2019.09.022.

SAN ANTONIO, TEX. – Some HIV-positive individuals on antiretroviral therapy continue to attempt blood donation, for reasons that may include ignorance of the risks of transmission, test-seeking behavior, or other unknown motivations to donate despite knowing their viral status, caution investigators who monitor the nation’s blood supply.

Additionally, evidence of pre-exposure prophylaxis (PrEP) with antiretroviral agents (ARV) in HIV-negative donors raises concerns about possible risk of transmission from HIV-breakthrough infections, reported Brian S. Custer, PhD, of Vitalant Research Institute.

Dr. Custer and colleagues in the U.S. Transfusion Transmissible Infections Monitoring System (TTIMS) evaluated plasma samples from four large blood collection organizations and found metabolites of drugs typically used in ARV regimens, at concentrations indicating that they had been taken within a week of blood donation.

“What are the motivations of these individuals who are ARV-positive and HIV-positive? Are they using the blood center as a place to monitor their infection status? We just do not know the answer to that, but it does bring back this issue of whether there a form of test seeking going on here,” he said at the annual meeting of AABB, the group formerly known as the American Association of Blood Banks.

The findings suggest that current donor health questionnaires and pre-donation screening are not adequate for ascertaining disclosure of HIV status or behaviors that could put the safety of the blood supply in doubt.
 

Does ‘U’ really equal ‘U’?

The public health message that “undetectable” equals “untransmittable” may help to prevent new infections, but may not translate into transfusion safety, Dr. Custer said.

Current HIV treatment guidelines recommend that infected individuals start on ARV immediately upon receiving a diagnosis. ARV drugs both suppress viremia and alter biomarkers of HIV progression, and may delay the time to antibody seroconversion, which could affect the ability to detect HIV through blood donation screening.

To see whether there is renewed cause for concern about safety of the blood supply, the TTIMS investigators tested for ARV metabolites in donated blood samples as a surrogate for HIV infection.

They looked at 299 HIV-positive plasma samples and 300 samples negative for all testable infections using liquid chromatography–mass spectometry for metabolites of 13 ARVs.

No ARV metabolites could be detected in the HIV-negative samples, but in 299 samples from 463 HIV-positive donors they found that 46 (15.4%) tested positive for ARVs. Of these 46 specimens, 43 were from first-time donors, and 34 were from males. Three samples were from repeat donors.

In all, 41 of the 46 ARV-positive donors would have been considered as potential “elite controllers” – HIV-infected individuals with no detectable viral loads in the absence of therapy – based on HIV-positive serology but negative nucleic acid test (NAT) results.

Samples from five first-time donors tested positive for HIV by both serology and NAT, and also contained ARV metabolites, suggesting that the donors had started ARVs recently, had suboptimal therapy, or were poorly adherent to their regimens.

PrEP use among HIV-negative donors

The investigators also looked at PrEP use in 1494 samples from first-time male donors that tested negative for all markers routinely screened: HIV 1/2, hepatitis B virus, hepatitis C virus, HTLV-I/II, West Nile virus, ZIKV, Treponema pallidum and Trypanosoma cruzi.

The donors came from Boston, Los Angeles, Miami, New York, San Francisco, and Washington, all cities with elevated HIV prevalence and active PrEP rollout campaigns.

They tested for analytes to emtricitabine and tenofovir, the two ARV components of the PrEP drug Truvada, and found that nine samples (0.6%) tested positive for PrEP. Of these, three donors had taken PrEP approximately 1 day before donation, two took it 2 days before, and four took it about 4 days before donation.

“There is quite a bit of concern about what this might mean for blood safety.” Dr. Custer said. “There’s a possibility of a breakthrough infection if someone is not PrEP adherent, and would we be able to detect them? Could this be an additional indicator for the risk of transfusion-transmissible infections? Could we identify subgroups of PrEP use in the donor population, and would we see any evidence?”
 

Mitigation Efforts

The National Heart, Lung, and Blood Institute is supporting a 7-year research project to study the potential impact of antiretroviral therapy and PrEP in the United States and Brazil under the Recipient Epidemiology and Donor Evaluation Study-IV-Pediatric (REDS-IV-P) project.

In addition, an AABB task force has drafted new questions for the donor health questionnaire intended to focus the attention of potential donors on PrEP, postexposure prophylaxis (PEP), and antiretroviral therapy.

In addition to asking about the use of medications on the deferral list, the proposed additions would ask, “In the past 16 weeks, have you taken any medication to prevent an HIV infection?” and “Have you EVER taken any medication to treat an HIV infection?”

TTIMS is supported by the U.S. Food and Drug Administration, NHLBI, and the Office of the Assistant Secretary for Health. Dr. Custer and all coinvestigators reported having no relevant disclosures.

SOURCE: : wit AABB 2019. Abstract PL5-MN4-32

SAN ANTONIO, TEX. – Some HIV-positive individuals on antiretroviral therapy continue to attempt blood donation, for reasons that may include ignorance of the risks of transmission, test-seeking behavior, or other unknown motivations to donate despite knowing their viral status, caution investigators who monitor the nation’s blood supply.

Additionally, evidence of pre-exposure prophylaxis (PrEP) with antiretroviral agents (ARV) in HIV-negative donors raises concerns about possible risk of transmission from HIV-breakthrough infections, reported Brian S. Custer, PhD, of Vitalant Research Institute.

Dr. Custer and colleagues in the U.S. Transfusion Transmissible Infections Monitoring System (TTIMS) evaluated plasma samples from four large blood collection organizations and found metabolites of drugs typically used in ARV regimens, at concentrations indicating that they had been taken within a week of blood donation.

“What are the motivations of these individuals who are ARV-positive and HIV-positive? Are they using the blood center as a place to monitor their infection status? We just do not know the answer to that, but it does bring back this issue of whether there a form of test seeking going on here,” he said at the annual meeting of AABB, the group formerly known as the American Association of Blood Banks.

The findings suggest that current donor health questionnaires and pre-donation screening are not adequate for ascertaining disclosure of HIV status or behaviors that could put the safety of the blood supply in doubt.
 

Does ‘U’ really equal ‘U’?

The public health message that “undetectable” equals “untransmittable” may help to prevent new infections, but may not translate into transfusion safety, Dr. Custer said.

Current HIV treatment guidelines recommend that infected individuals start on ARV immediately upon receiving a diagnosis. ARV drugs both suppress viremia and alter biomarkers of HIV progression, and may delay the time to antibody seroconversion, which could affect the ability to detect HIV through blood donation screening.

To see whether there is renewed cause for concern about safety of the blood supply, the TTIMS investigators tested for ARV metabolites in donated blood samples as a surrogate for HIV infection.

They looked at 299 HIV-positive plasma samples and 300 samples negative for all testable infections using liquid chromatography–mass spectometry for metabolites of 13 ARVs.

No ARV metabolites could be detected in the HIV-negative samples, but in 299 samples from 463 HIV-positive donors they found that 46 (15.4%) tested positive for ARVs. Of these 46 specimens, 43 were from first-time donors, and 34 were from males. Three samples were from repeat donors.

In all, 41 of the 46 ARV-positive donors would have been considered as potential “elite controllers” – HIV-infected individuals with no detectable viral loads in the absence of therapy – based on HIV-positive serology but negative nucleic acid test (NAT) results.

Samples from five first-time donors tested positive for HIV by both serology and NAT, and also contained ARV metabolites, suggesting that the donors had started ARVs recently, had suboptimal therapy, or were poorly adherent to their regimens.

PrEP use among HIV-negative donors

The investigators also looked at PrEP use in 1494 samples from first-time male donors that tested negative for all markers routinely screened: HIV 1/2, hepatitis B virus, hepatitis C virus, HTLV-I/II, West Nile virus, ZIKV, Treponema pallidum and Trypanosoma cruzi.

The donors came from Boston, Los Angeles, Miami, New York, San Francisco, and Washington, all cities with elevated HIV prevalence and active PrEP rollout campaigns.

They tested for analytes to emtricitabine and tenofovir, the two ARV components of the PrEP drug Truvada, and found that nine samples (0.6%) tested positive for PrEP. Of these, three donors had taken PrEP approximately 1 day before donation, two took it 2 days before, and four took it about 4 days before donation.

“There is quite a bit of concern about what this might mean for blood safety.” Dr. Custer said. “There’s a possibility of a breakthrough infection if someone is not PrEP adherent, and would we be able to detect them? Could this be an additional indicator for the risk of transfusion-transmissible infections? Could we identify subgroups of PrEP use in the donor population, and would we see any evidence?”
 

Mitigation Efforts

The National Heart, Lung, and Blood Institute is supporting a 7-year research project to study the potential impact of antiretroviral therapy and PrEP in the United States and Brazil under the Recipient Epidemiology and Donor Evaluation Study-IV-Pediatric (REDS-IV-P) project.

In addition, an AABB task force has drafted new questions for the donor health questionnaire intended to focus the attention of potential donors on PrEP, postexposure prophylaxis (PEP), and antiretroviral therapy.

In addition to asking about the use of medications on the deferral list, the proposed additions would ask, “In the past 16 weeks, have you taken any medication to prevent an HIV infection?” and “Have you EVER taken any medication to treat an HIV infection?”

TTIMS is supported by the U.S. Food and Drug Administration, NHLBI, and the Office of the Assistant Secretary for Health. Dr. Custer and all coinvestigators reported having no relevant disclosures.

SOURCE: : wit AABB 2019. Abstract PL5-MN4-32

SAN ANTONIO, TEX. – Some HIV-positive individuals on antiretroviral therapy continue to attempt blood donation, for reasons that may include ignorance of the risks of transmission, test-seeking behavior, or other unknown motivations to donate despite knowing their viral status, caution investigators who monitor the nation’s blood supply.

Additionally, evidence of pre-exposure prophylaxis (PrEP) with antiretroviral agents (ARV) in HIV-negative donors raises concerns about possible risk of transmission from HIV-breakthrough infections, reported Brian S. Custer, PhD, of Vitalant Research Institute.

Dr. Custer and colleagues in the U.S. Transfusion Transmissible Infections Monitoring System (TTIMS) evaluated plasma samples from four large blood collection organizations and found metabolites of drugs typically used in ARV regimens, at concentrations indicating that they had been taken within a week of blood donation.

“What are the motivations of these individuals who are ARV-positive and HIV-positive? Are they using the blood center as a place to monitor their infection status? We just do not know the answer to that, but it does bring back this issue of whether there a form of test seeking going on here,” he said at the annual meeting of AABB, the group formerly known as the American Association of Blood Banks.

The findings suggest that current donor health questionnaires and pre-donation screening are not adequate for ascertaining disclosure of HIV status or behaviors that could put the safety of the blood supply in doubt.
 

Does ‘U’ really equal ‘U’?

The public health message that “undetectable” equals “untransmittable” may help to prevent new infections, but may not translate into transfusion safety, Dr. Custer said.

Current HIV treatment guidelines recommend that infected individuals start on ARV immediately upon receiving a diagnosis. ARV drugs both suppress viremia and alter biomarkers of HIV progression, and may delay the time to antibody seroconversion, which could affect the ability to detect HIV through blood donation screening.

To see whether there is renewed cause for concern about safety of the blood supply, the TTIMS investigators tested for ARV metabolites in donated blood samples as a surrogate for HIV infection.

They looked at 299 HIV-positive plasma samples and 300 samples negative for all testable infections using liquid chromatography–mass spectometry for metabolites of 13 ARVs.

No ARV metabolites could be detected in the HIV-negative samples, but in 299 samples from 463 HIV-positive donors they found that 46 (15.4%) tested positive for ARVs. Of these 46 specimens, 43 were from first-time donors, and 34 were from males. Three samples were from repeat donors.

In all, 41 of the 46 ARV-positive donors would have been considered as potential “elite controllers” – HIV-infected individuals with no detectable viral loads in the absence of therapy – based on HIV-positive serology but negative nucleic acid test (NAT) results.

Samples from five first-time donors tested positive for HIV by both serology and NAT, and also contained ARV metabolites, suggesting that the donors had started ARVs recently, had suboptimal therapy, or were poorly adherent to their regimens.

PrEP use among HIV-negative donors

The investigators also looked at PrEP use in 1494 samples from first-time male donors that tested negative for all markers routinely screened: HIV 1/2, hepatitis B virus, hepatitis C virus, HTLV-I/II, West Nile virus, ZIKV, Treponema pallidum and Trypanosoma cruzi.

The donors came from Boston, Los Angeles, Miami, New York, San Francisco, and Washington, all cities with elevated HIV prevalence and active PrEP rollout campaigns.

They tested for analytes to emtricitabine and tenofovir, the two ARV components of the PrEP drug Truvada, and found that nine samples (0.6%) tested positive for PrEP. Of these, three donors had taken PrEP approximately 1 day before donation, two took it 2 days before, and four took it about 4 days before donation.

“There is quite a bit of concern about what this might mean for blood safety.” Dr. Custer said. “There’s a possibility of a breakthrough infection if someone is not PrEP adherent, and would we be able to detect them? Could this be an additional indicator for the risk of transfusion-transmissible infections? Could we identify subgroups of PrEP use in the donor population, and would we see any evidence?”
 

Mitigation Efforts

The National Heart, Lung, and Blood Institute is supporting a 7-year research project to study the potential impact of antiretroviral therapy and PrEP in the United States and Brazil under the Recipient Epidemiology and Donor Evaluation Study-IV-Pediatric (REDS-IV-P) project.

In addition, an AABB task force has drafted new questions for the donor health questionnaire intended to focus the attention of potential donors on PrEP, postexposure prophylaxis (PEP), and antiretroviral therapy.

In addition to asking about the use of medications on the deferral list, the proposed additions would ask, “In the past 16 weeks, have you taken any medication to prevent an HIV infection?” and “Have you EVER taken any medication to treat an HIV infection?”

TTIMS is supported by the U.S. Food and Drug Administration, NHLBI, and the Office of the Assistant Secretary for Health. Dr. Custer and all coinvestigators reported having no relevant disclosures.

SOURCE: : wit AABB 2019. Abstract PL5-MN4-32