The researchers followed up with the participants via self-reports, electronic drug monitoring devices that recorded pill bottles being opened, and dried blood samples or peripheral blood mononuclear cells that revealed whether there were adequate concentrations of the PrEP medications in participants’ systems. In-person clinic visits took place weekly in the early stages and tapered off to roughly once a month for the duration of the trial. The goal was to ensure that study subjects had sufficient coverage for all instances of sexual intercourse via their ingestion of PrEP.
By offering non-daily PrEP regimens, providers can acknowledge that an individual’s sex life may change over time, Robert M Grant, MD, MPH, a professor at the University of California, San Francisco School of Medicine and the lead author of the study, told Contagion®. “People move into and out of seasons of HIV exposure, depending on their relationship status, their substance use, their housing, their employment and so much else,” he said. A non-daily PrEP regimen allows users to easily start and stop the medication depending on their needs.
However, the results of the ADAPT study highlight the need for strong support for patients who stray from the conventional daily-PrEP regimen. In the Bangkok cohort, participants in the daily-dosing arm of the trial achieved an 85% coverage of sexual events, with the twice-a-week cohort seeing an 84% coverage rate. Participants who took PrEP before and after sex saw a 74% coverage rate. The Harlem participants, however, fared much worse: 66% of those taking PrEP daily were covered for sexual events, 47% of the twice-a-week arm were covered, and 52% of those taking PrEP before and after sex were covered.
Why was there such a discrepancy in the coverage rates between the cohorts? “The Bangkok site had extensive experience with gay and bisexual men and transgender women,” Dr. Grant said. “They had been providing high-quality clinical and social services for many years, and this research was built into that framework of trust. In contrast, the Harlem site only does research, and they were working with young men of color for the first time. We have seen how PrEP use is typically highly effective when offered by community-based organizations, while research sites struggle with adherence.”
PrEP’s side effects include nausea, fatigue, gastrointestinal upsets, and headache. The 2 study cohorts experienced no significant differences in neurological or gastrointestinal side effects, although the daily-dose group at both study sites seemed to suffer more side effects around week 10. After week 10, the Bangkok group experienced fewer neurological side effects while Harlem’s were unchanged. Participants in both study sites suffered fewer gastrointestinal side effects after week 10.
The ADAPT study took place before the results of a similar study, the Ipergay study, were available. The Ipergay study, conducted in France and Canada, similarly concluded that non-daily dosing with PrEP was effective in protecting against HIV. As this wasn’t known for sure at the time the ADAPT study was getting underway, the ADAPT study participants were told that daily dosing was effective but that non-daily dosing was experimental. Because of this, the ADAPT study researchers feel that adherence to the non-daily regimens could have been compromised. Had the results of the Ipergay study been available at the time, the ADAPT researchers would have altered the dosing recommendations for the event-driven arm: Instead of recommending one dose before and one dose after sex, participants would have been instructed to take 2 tablets 2 to 24 hours before sex, another tablet the day after sex, and an additional tablet 2 days after sex. “That is important because the post-sex doses are the most likely to be missed,” Dr. Grant said.
According to Dr. Grant, the US Food and Drug Administration and Centers for Disease Control and Prevention still recommend daily dosing with PrEP because drug companies have not yet submitted the results of PrEP dosing studies for review. However, as providers have the leeway to prescribe medications as they see fit, the hope is that better communication between patients and providers will allow for non-daily PrEP dosing regimens that best fit the lifestyles of each user.