FDA NewsPerspective

FDA approves Truvada for PrEP in teenagers

Based on findings from a single-arm, open-label clinical trial, the FDA has approved Truvada for use as an HIV-1 pre-exposure prophylaxis option for teenagers who weigh at least 35 kg, according to an update issued by the organization.

This approval of Truvada (tenofovir disoproxil fumarate/emtricitabine [TDF/FTC], Gilead Sciences) expands options for adolescents who test negative for HIV-1 before beginning pre-exposure prophylaxis (PrEP). The FDA notes that if a patient presents with clinical symptoms associated with acute viral infection and the patient has a suspected exposure occurring less than 1 month from the visit, PrEP should be postponed for a minimum of 1 month. This provides time for reconfirming HIV-1 status.

“Study ATN113 has demonstrated that Truvada for PrEP is a well-tolerated prevention option for adolescents who are vulnerable to HIV,” Sybil Hosek, PhD, clinical psychologist at the Cook County Health and Hospital System’s Stroger Hospital, Chicago, said in a press release from Gilead Sciences. “In addition to traditional risk-reduction strategies, health care providers and community advocates are now equipped with another tool to help address the incidence of HIV in younger at-risk populations.”

Adolescents and adults who have had a partner with known HIV-1 infection and have had sexual activity in an area or social network with a high disease burden are at increased risk of infection and could be considered for PrEP. Furthermore, the FDA states that consideration should also be given to those who use condoms inconsistently or do not use them; have previously had a sexually transmitted infection; receives food, money, shelter or drugs in exchange for sex; are incarcerated; and who have a partner with unknown HIV-1 status but have any other associated risk factor.

In ATN113, 67 adolescent men who have sex with men and were aged between 15 and 18 years were administered TDF/FTC once daily for a median of 47 weeks. Of these participants, 46% were Hispanic, 52% were black and 37% were white. The safety of the drug in adolescents was comparable to the safety profile of the PrEP option in adults. Additionally, when those uninfected with HIV-1 used TDF/FTC, their bone mineral density increased by the 48th week, with a 2.58% increase observed for lumbar spine and 0.72% for total body.

Although most patients improved when taking PrEP, one patient decreased their total body bone mineral density by more than 4% by week 24. Three other patients had decreased bone mineral density z-scores at week 24 or 48. Although these negative effects were observed, the researchers note that low rates of adherence may contribute to these data by the 48th week.

“We must make use of all available options when considering HIV prevention strategies, and we welcome the development that Truvada for PrEP is now available for younger people who are at risk of HIV,” Matthew Rose, policy and advocacy manager at NMAC, a Washington-based advocacy organization, said in the release. “We will continue to build awareness and understanding of the role of Truvada for PrEP as part of a comprehensive HIV prevention plan for all who may benefit from it, particularly among communities disproportionately impacted by the disease, including young black and Latino men in the United States.”

In addition to the safety of TDF/FTC, the researchers also examined adherence and resistance. Seroconversion was observed in three participants, all of whom poorly adhered to PrEP based on TDF levels in dried blood spot assays. When these patients were further assessed, the researchers observed no TDF- or FTC-associated HIV-1 resistance substitutions in the carried virus.

Overall, adherence to Truvada was low among adolescents, with significant decreases in use observed by the 12th week when they switched from monthly to quarterly visits. These results, according to the researchers, imply that teenagers using PrEP should receive more regular visits.

Despite that information was available for the safety profile of TDF/FTC in adolescents, no information was available for the drug’s pharmacokinetic profile.

“By expanding the number of at-risk individuals who can consider Truvada as a prevention option, we have taken another important step toward helping to reduce HIV transmission rates and improve public health in the U.S.,” Andrew Cheng, MD, PhD, chief medical officer at Gilead Sciences, said in the release. “Gilead is committed to addressing unmet needs in HIV prevention and treatment, and we look forward to continuing that work with our research and advocacy partners.”

Resource: http://www.gilead.com/news/press-releases/2018/5/us-food-and-drug-administration-approves-expanded-indication-for-truvada-emtricitabine-and-tenofovir-disoproxil-fumarate-for-reducing-the-risk-of-acquiring-hiv1-in-adolescents

Based on findings from a single-arm, open-label clinical trial, the FDA has approved Truvada for use as an HIV-1 pre-exposure prophylaxis option for teenagers who weigh at least 35 kg, according to an update issued by the organization.

This approval of Truvada (tenofovir disoproxil fumarate/emtricitabine [TDF/FTC], Gilead Sciences) expands options for adolescents who test negative for HIV-1 before beginning pre-exposure prophylaxis (PrEP). The FDA notes that if a patient presents with clinical symptoms associated with acute viral infection and the patient has a suspected exposure occurring less than 1 month from the visit, PrEP should be postponed for a minimum of 1 month. This provides time for reconfirming HIV-1 status.

“Study ATN113 has demonstrated that Truvada for PrEP is a well-tolerated prevention option for adolescents who are vulnerable to HIV,” Sybil Hosek, PhD, clinical psychologist at the Cook County Health and Hospital System’s Stroger Hospital, Chicago, said in a press release from Gilead Sciences. “In addition to traditional risk-reduction strategies, health care providers and community advocates are now equipped with another tool to help address the incidence of HIV in younger at-risk populations.”

Adolescents and adults who have had a partner with known HIV-1 infection and have had sexual activity in an area or social network with a high disease burden are at increased risk of infection and could be considered for PrEP. Furthermore, the FDA states that consideration should also be given to those who use condoms inconsistently or do not use them; have previously had a sexually transmitted infection; receives food, money, shelter or drugs in exchange for sex; are incarcerated; and who have a partner with unknown HIV-1 status but have any other associated risk factor.

In ATN113, 67 adolescent men who have sex with men and were aged between 15 and 18 years were administered TDF/FTC once daily for a median of 47 weeks. Of these participants, 46% were Hispanic, 52% were black and 37% were white. The safety of the drug in adolescents was comparable to the safety profile of the PrEP option in adults. Additionally, when those uninfected with HIV-1 used TDF/FTC, their bone mineral density increased by the 48th week, with a 2.58% increase observed for lumbar spine and 0.72% for total body.

Although most patients improved when taking PrEP, one patient decreased their total body bone mineral density by more than 4% by week 24. Three other patients had decreased bone mineral density z-scores at week 24 or 48. Although these negative effects were observed, the researchers note that low rates of adherence may contribute to these data by the 48th week.

“We must make use of all available options when considering HIV prevention strategies, and we welcome the development that Truvada for PrEP is now available for younger people who are at risk of HIV,” Matthew Rose, policy and advocacy manager at NMAC, a Washington-based advocacy organization, said in the release. “We will continue to build awareness and understanding of the role of Truvada for PrEP as part of a comprehensive HIV prevention plan for all who may benefit from it, particularly among communities disproportionately impacted by the disease, including young black and Latino men in the United States.”

In addition to the safety of TDF/FTC, the researchers also examined adherence and resistance. Seroconversion was observed in three participants, all of whom poorly adhered to PrEP based on TDF levels in dried blood spot assays. When these patients were further assessed, the researchers observed no TDF- or FTC-associated HIV-1 resistance substitutions in the carried virus.

Overall, adherence to Truvada was low among adolescents, with significant decreases in use observed by the 12th week when they switched from monthly to quarterly visits. These results, according to the researchers, imply that teenagers using PrEP should receive more regular visits.

Despite that information was available for the safety profile of TDF/FTC in adolescents, no information was available for the drug’s pharmacokinetic profile.

“By expanding the number of at-risk individuals who can consider Truvada as a prevention option, we have taken another important step toward helping to reduce HIV transmission rates and improve public health in the U.S.,” Andrew Cheng, MD, PhD, chief medical officer at Gilead Sciences, said in the release. “Gilead is committed to addressing unmet needs in HIV prevention and treatment, and we look forward to continuing that work with our research and advocacy partners.”

Resource: http://www.gilead.com/news/press-releases/2018/5/us-food-and-drug-administration-approves-expanded-indication-for-truvada-emtricitabine-and-tenofovir-disoproxil-fumarate-for-reducing-the-risk-of-acquiring-hiv1-in-adolescents

    Perspective

    Robert Welliver

    On May 16, 2018, the FDA approved the use of Truvada for pre-exposure prevention of HIV-1 infection in adolescents weighing at least 35 kg. Both of the drugs in the compound are nucleoside/nucleotide analog inhibitors of viral reverse transcriptase and have established effectiveness against HIV.

    The combination drug was previously approved for the same indication in adults in 2012. Studies have demonstrated that, when taken continuously on a once-daily basis, the combination drug offers up to 90% effectiveness in preventing acquisition of HIV infection via sexual contact, and 70% effectiveness against infection via drug injection.

    Data published in 2016 indicated that the 13 years to 24 years age group accounts for 21% of new HIV infections in the United States, with 81% of these infections occurring in young men who have sex with men (CDC). The drug may be particularly useful for HIV-negative persons in relationships with HIV-infected partners, and in communities where the risk for acquiring HIV infection is known to be increased.

    The most common side effects are generally mild, and include headache, nausea, and abdominal pain. Less common effects include lactic acidosis, thinning of bone density, hepatitis, and exacerbation of pre-existing hepatitis B infection, among other issues. Individuals for whom prophylaxis is being considered should have a negative HIV screening test, and no symptoms compatible with HIV infection before starting the medication.

    The use of this drug does not replace the need for other HIV prevention measures, including knowing one’s prospective partner well, use of condoms, avoiding recreational drug injection and generally considering the risks of one’s actions.

    • Robert Welliver, MD
    • Chief of the section of Pediatric Infectious Diseases, department of pediatrics
      University of Oklahoma College of Medicine

    Disclosures: Welliver reports no relevant financial disclosures.