A new U.S. study reinforces that on-demand pre-exposure prophylaxis (PrEP) is an effective HIV prevention strategy for those who don’t want the more common daily dosing. In the study, published last week in the journal Clinical Infectious Diseases, researchers followed 279 male Kaiser Permanente patients in San Francisco for three months of 2-1-1 dosing. They found that none of the patients contracted HIV during the study period, and few reported missed doses.
PrEP 2-1-1 involves taking a double dose of emtricitabine/tenofovir disoproxil fumarate (Truvada) between two and 24 hours before anticipated sex, one dose 24 hours after the initial double dose, and a final dose 24 hours after that.
Carlo Hojilla, Ph.D., RN, a research fellow with the Kaiser Permanente Northern California Division of Research and one of the authors of the study, told TheBody that 2-1-1 dosing, when used as directed, is safe and effective at preventing HIV, and a “good strategy for those reluctant to take a daily dose.”
The Kaiser study provides one of the first major sets of data that demonstrate the effectiveness of 2-1-1 dosing from the United States. Recent studies from France and the Netherlands have also shown that 2-1-1—PrEP taken before and after sex—works at preventing HIV for men who have sex with men, regardless of the frequency of sex.
Clients in the Kaiser study who were already on daily PrEP were told about PrEP 2-1-1 and given an opportunity to switch; those starting PrEP could choose between the on-demand or daily regimen. Three-quarters had previously used PrEP, including 11 men who had used the 2-1-1 regimen before Kaiser started offering it and six who had used other nondaily schedules, such as taking PrEP only when on vacation. All but six of the men who were prescribed on-demand PrEP completed their three-month follow-up visit. Of these, 51% exclusively used the 2-1-1 regimen during that period, 19% switched to a daily dose, 15% used a combination of daily and 2-1-1, and 3% never started PrEP.
Approximately 14% of the men reported challenges using the 2-1-1 regimen, including forgetting the dosing regimen, not planning for sex in advance, and side effects. Twenty men discontinued PrEP due to loss of health insurance, reduced sexual risk, or side effects.
Among the 181 men who used the 2-1-1 regimen exclusively or in combination with daily dosing, only 4% reported missing a dose of Truvada the last time they had sex. On average, they used one course of PrEP 2-1-1—or four pills—during a month. “Our results did show a low number of challenges with 2-1-1, and those who did have challenges switched over to daily PrEP,” Hojilla said.
Hojilla admitted that the study has some limitations: It’s not clear what sexual activities or sexual positions the study participants engaged in, which could make a difference in their risk of HIV. Gauging precise reasons for adherence issues was also difficult. “The question was phrased, ‘Did you miss any doses?’” Hojilla said; “5.9% said that they did, or they had trouble remembering when to take a dose, but that’s a pretty low number.” Hojilla added that no subjects initiated PEP (post-exposure prophylaxis), suggesting nobody who skipped a dose had engaged in risk exposure.
Kaiser San Francisco started offering 2-1-1 PrEP in February 2019. The San Francisco AIDS Foundation’s Magnet sexual health service at Strut began offering 2-1-1 a month later. The World Health Organization and the International Antiviral Society-USA have endorsed on-demand PrEP for men who have sex with men, but the U.S. Food and Drug Administration has not approved the regimen, mainly because it has not yet been studied in cisgender (non-transgender) women or transgender men. Study results for cisgender men only apply to Truvada, not emtricitabine/tenofovir alafenamide (Descovy), which was approved last year as an alternative daily PrEP option.
There is no data on how many U.S. medical professionals are prescribing PrEP 2-1-1, but Hyman Scott, M.D., M.P.H., medical director for clinical research at Bridge HIV in the San Francisco Department of Public Health, said few providers feel empowered to counsel for 2-1-1 and therefore only prescribe Truvada or Descovy for daily use, if they prescribe it at all.
“Counseling is more complex for 2-1-1,” Scott said. “And we are still working on expanding daily PrEP now, eight years after [Truvada] approval, and we’re continuing to encourage and expand that.”
Scott noted that people go back and forth between 2-1-1 and daily PrEP, depending on their sexual needs, regardless of what their providers say.
Hojilla agrees that often patients are savvier than their doctors about dosing, and that some will adopt alternate regimens, including T’s and S’s, which is four days a week, on Tuesdays, Thursdays, Saturdays, and Sundays, or vacation dosing. “What’s needed are some clear regulatory guidelines for intermittent PrEP use. There’s still a hesitation for doctors to prescribe, and a lack of guidance is a barrier to implementation,” Hojilla said.
The Centers for Disease Control and Prevention has estimated that more than a million people in the U.S. could benefit from PrEP. But since its introduction in 2012, prescriptions have lagged far behind the need, especially for the most vulnerable populations, including Black and Latinx men and transgender women. Globally, PrEP use is lagging too: It’s estimated that PrEP use is one-tenth of the World Health Organization’s goal of 3 million PrEP users by 2020.