A clinical study funded by the National Institutes of Health has found that young, single black women in South Africa adhered to a daily pill regimen to prevent HIV infection-an HIV prevention strategy known as pre-exposure prophylaxis, or PrEP. This finding is the first strong indication that this population at substantial HIV risk could accept and reliably adhere to daily PrEP dosing. Men who have sex with men (MSM) and transgender women (TGW) in New York and Thailand also successfully adhered to daily dosing.
PrEP-which consists of a daily dose of two antiretrovirals, tenofovir and emtricitabine, in a single pill marketed as Truvada-prevents HIV infection when taken consistently. Although some previous placebo-controlled PrEP clinical trials in women in sub-Saharan Africa had found challenges with adherence, 76 percent of women assigned to take PrEP on a daily basis in the HIV Prevention Trials Network (HPTN) 067 study adhered to the prescribed regimen. MSM and TGW from Harlem and Bangkok who participated in the study adhered to the daily regimen 65 percent and 85 percent of the time, respectively.
Several investigators involved presented the key findings from the HPTN 067 trial, also known as the Alternative Dosing to Augment Pre-Exposure Prophylaxis Pill Taking (ADAPT) study, today at the 8th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention in Vancouver, Canada.
"These are encouraging findings, demonstrating that if given access to Truvada, women and men will take it daily to prevent HIV infection," Anthony S. Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases at NIH, said. "This study takes a solid step toward connecting people at particularly high-risk for HIV with a proven prevention strategy that can protect them from infection."
HPTN 067, a Phase II clinical study that began in 2013, was designed to identify the PrEP pill-taking schedules that people are most likely to follow. The study involved 179 women with a median age of 26 in Cape Town, South Africa; 179 black MSM and TGW in Harlem, New York; and 178 Thai MSM and TGW in Bangkok. Median ages of the Harlem and Bangkok participants was 30 and 31, respectively. HIV incidence in all of these populations is high. Study participants at the three sites were randomly assigned into three groups, each prescribed Truvada, with instructions and counseling to take the pill on either a daily schedule or one of two non-daily schedules for 24 weeks. The two non-daily schedules involved taking one pill either twice per week and another after sex, or one pill before and another after sex. Adherence was measured by techniques that included self-reporting, blood and hair analyses, and data from Wisepill devices, which record opening of pill cases. At all three study sites, adherence to the daily regimen was higher than adherence to the two non-daily regimens.
Those enrolled in this open-label study were educated about the efficacy of daily PrEP and knew they were taking active drugs rather than placebo. Because daily use of PrEP is the only regimen approved by the U.S. Food and Drug Administration and recommended by the U.S. Centers for Disease Control and Prevention, all participants were provided with HIV risk reduction counseling and offered condoms. Study participants who became infected during the course of the study were referred to local medical care for treatment.
"This is an important step forward for optimizing HIV prevention strategies for people who would otherwise be at high risk for acquiring HIV infection," said Robert M. Grant, M.D., M.P.H., of the Gladstone Institutes and the University of California, San Francisco and study chair. "The findings will inform the next generation of PrEP research and the development of best practices regarding PrEP adherence and counseling."
During in-depth interviews at the Cape Town study site, the women reported that daily dosing was the easiest regimen to follow, as taking a pill each day established a simple-to-follow habit at a convenient time. Focus groups of enrolled participants also indicated that community support and reminders delivered via cell phones aided adherence.
Similar to the finding in South African women, MSM and TGW participants in New York and Thailand were most likely to take PrEP as directed when prescribed a daily dose. Participants at the Harlem site were predominantly black MSM, and average adherence was 65 percent when daily PrEP was prescribed. Adherence was significantly lower among those taking the non-daily PrEP regimens, with fewer than half of the participants sticking to the dosing schedule.
MSM and TGW in Bangkok had the highest success with daily dosing with 85 percent taking the pills as instructed, while 79 percent took the twice-weekly pills combined with one pill after sex, and 65 percent took the schedule that involved one pill before and after sex. However, there were challenges in adhering to non-daily dosing, and it is unknown if these regimens work to prevent HIV infection.
Daily oral PrEP dosing has proven effective at reducing the risk of HIV infection in multiple clinical trials. Both FDA approval and CDC guidelines are based on multiple large international clinical trials examining daily PrEP among different populations, including MSM, high-risk heterosexual women and men, and people who inject drugs.
"HPTN 067 showed that daily dosing was the easiest PrEP regimen to follow. This is important and encouraging news, since we know that PrEP offers high levels of protection against HIV when taken daily," said Jonathan Mermin, M.D., director of the National Center for HIV/AIDS, Viral Hepatitis, STD, and Tuberculosis Prevention at CDC.
HPTN 067 was conducted by investigators from the NIH-funded HPTN at the Emavundleni Center in Cape Town and the Harlem Prevention Center in New York. CDC conducted the Bangkok arm of the study in collaboration with the Bangkok Metropolitan Administration and the Thailand Ministry of Public Health. In addition to NIAID support, funding for HPTN 067 came from the National Institute of Mental Health and the Office of AIDS Research at NIH. The Truvada used in the study was donated by Gilead Sciences, Inc.
For more information about HPTN 067, visit ClinicalTrials.gov using study identifier NCT01327651.