October 11, 2013
IAVI-Supported Study in Uganda Explores Safety, Adherence for Intermittent Oral ARV-Based PrEP among HIV Serodiscordant Couples
New York – New clinical trial findings in Uganda highlight the feasibility of intermittent treatment with pre-exposure prophylaxis (PrEP) for HIV prevention in HIV serodiscordant couples, where only one partner is HIV-positive.
Encouraging safety and adherence data from this Phase I/II study show that taking PrEP less than once per day may be a potential alternative to daily treatment, which poses a long-term challenge as ensuring daily adherence among healthy people may be difficult. PLOS ONE, the scientific journal of the Public Library of Science, published findings from the study – which was conducted by researchers at the Medical Research Council (MRC) / Uganda Virus Institute (UVRI) Uganda Research Unit on AIDS in Entebbe, Uganda, and was sponsored by the International AIDS Vaccine Initiative (IAVI) – in September 2013. The antiretroviral drug used in the study, Truvada – a combination of tenofovir and emtricitabine – was provided by the manufacturer, Gilead Sciences. Truvada was approved by the U.S. Food & Drug Administration (FDA) for daily use as PrEP after this study had ended.
“PrEP is one of several preventive options helping to stem the tide of HIV, but we don’t know enough about whether daily dosing will be achievable in various populations,” said Frances Priddy, Chief Medical Officer and Executive Director for Medical Affairs at IAVI. “This study suggests that an intermittent dosing regimen can be acceptable and have high adherence.”
Seventy-two HIV-negative volunteers (36 men and 36 women) in HIV serodiscordant relationships enrolled in the study together with their partners. Each participant was randomized to take a single Truvada pill or a placebo, either daily or intermittently (Mondays and Fridays, and within two hours of having sex, not to exceed one dose per day). Over six months, researchers conducted safety assessments on a monthly basis and monitored adherence, as well as sexual activity, through a combination of the medication event monitoring system in which a microchip in the cap covering the pill bottle electronically recorded every time the bottle was opened and closed, patient self-reports and daily short message service (SMS) text messages.
Both intermittent and daily oral PrEP regimens were well-tolerated, with no safety concerns. Adherence to the twice weekly doses in the intermittent regimen and to the daily PrEP regimen was high (91 percent and 98 percent, respectively), although volunteers exhibited lower adherence to dosing after sex (45 percent).
A similar study conducted in Kenya among men who have sex with men and female sex workers was the first to explore intermittent antiretroviral PrEP use in humans, but found that rates of adherence were lower for intermittent versus daily dosing.
IAVI and its partners initiated this trial to explore adherence to PrEP in the high-risk populations that are expected to participate in HIV vaccine efficacy trials. “This data adds to our existing knowledge about the use of PrEP for HIV prevention, specifically among HIV discordant couples in Africa,” said Anatoli Kamali, study co-author and clinical researcher at MRC/UVRI in Entebbe, Uganda. “Given the cost, accessibility and adherence concerns associated with PrEP administered on a daily basis, intermittent PrEP regimens could be a desirable alternative but more research is needed to evaluate efficacy of these regimens.”
The AIDS pandemic ranks among the most devastating ever recorded in history. Since its start, more than 70 million people have been infected with HIV and some 35 million have died from HIV-related causes. A comprehensive response that combines proven, existing HIV-prevention methods, ARV treatment for people currently living with HIV, and the development and widespread use of new HIV-prevention technologies will be essential to ending the devastation wrought by HIV and AIDS. Ending the AIDS pandemic remains one of the biggest challenges of our time, and developing effective tools for the prevention of HIV will require sustained political, social and financial commitment and support.