NIH-sponsored clinical trials examine safety, acceptability of HIV antiretroviral medicines

Two new clinical trials are examining the safety and acceptability of antiretroviral medicines administered via injection as a means of protecting against HIV infection. The studies are being funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, and conducted by the NIAID-funded HIV Prevention Trials Network (HPTN).

The oral anti-HIV medication Truvada (a combination of emtricitabine and tenofovir disoproxil fumarate), made by Gilead Sciences, is currently the only antiretroviral drug approved by the U.S. Food and Drug Administration for daily use to prevent HIV infection. Truvada is also approved by the FDA for HIV treatment. Studies have shown, however, that some people at greatest risk for HIV infection may have difficulty adhering to a daily pill regimen to protect against HIV acquisition--an approach called pre-exposure prophylaxis, or PrEP. Therefore, researchers have pursued long-acting formulations of antiretroviral drugs that can be given much less frequently, with the hope of improving adherence.

"A safe, long-acting, injectable antiretroviral capable of protecting against HIV acquisition may serve as an attractive and feasible alternative to a daily pill for some individuals at highest risk for HIV infection and could, therefore, be a powerful HIV prevention tool," said NIAID Director Anthony S. Fauci, M.D.

The HPTN 076 trial, which will be conducted in South Africa, the United States and Zimbabwe, is a Phase 2 study to evaluate the safety and acceptability of rilpivirine LA, a long-acting injectable form of the FDA-approved antiretroviral drug rilpivirine (TMC278) from Janssen Sciences Ireland UC. The study is expected to enroll 132 women ages 18 to 45 years who are not infected with HIV and who are considered at low-risk for HIV infection. Volunteers will be randomly assigned to the rilpivirine LA study arm (88 study participants) or a placebo (44 study participants). Those participants assigned to receive the active product will first receive an oral tablet of rilpivirine (25 mg) to be taken once daily for four weeks, followed by two gluteal, intramuscular injections of rilpivirine LA at eight-week intervals for 10 months. Study participants assigned to the placebo group will first receive daily oral placebo for four weeks followed by two gluteal, intramuscular placebo injections once every eight weeks for 10 months. Study participants will be counseled at each clinic visit on how to protect against HIV infection. After the treatment period, study participants will be followed for eight months after the last set of injections to evaluate their effect. PATH, an international nonprofit organization based in Seattle, is the regulatory sponsor of the HPTN 076 trial. It is being conducted in collaboration with Janssen Sciences Ireland UC and NIAID.

The HPTN 077 Phase 2 trial, sponsored by NIAID, will evaluate the safety, pharmacokinetics, and acceptability of injectable GSK1265744 (cabotegravir), an investigational antiretroviral drug from GlaxoSmithKline (GSK) that is being simultaneously developed for both HIV treatment and prevention in oral and injectable form. In recently published results, GSK1265744 proved effective at protecting 12 of 14 female monkeys from a simian form of HIV when administered via injection.

The HPTN 077 study, which will be conducted at eight sites in Brazil, Malawi, South Africa and the United States, is expected to enroll 176 HIV-uninfected men and women between the ages of 18 to 65. Participants will be randomly assigned to one of two groups: one group will receive a daily oral tablet of GSK1265744 or an oral placebo for four weeks, followed by a one-week break to assess safety and tolerability. If no safety concerns are identified, participants will receive two gluteal intramuscular injections (a total of six injections) of the investigational drug or placebo injections at three site visits over the course of six months. Study participants will be counseled at each clinic visit on how to protect against HIV infection. Participants will be followed for a year after their last injection. The HPTN 077 trial is being conducted in collaboration with GSK and ViiV Healthcare.

"In the absence of an effective HIV vaccine, these studies mark an important step in our quest to find the best HIV prevention strategies that have the potential to bring the HIV epidemic to a halt," said Myron Cohen, M.D., HPTN principal investigator.

Both trials are expected to be completed in 2017.