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doi:doi: 10.12788/jfp.0207

Clinical Inquiries

Is event-driven PrEP dosing for HIV as effective as daily dosing?

J Fam Pract. 2021 June;70(5):253-255 | doi: 10.12788/jfp.0207

By

Tory Olsen, MD

Zachary Lally-Montgomery, PharmD

Gary Kelsberg, MD

Sarah Safranek, MLIS

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EVIDENCE-BASED ANSWER:

Probably, although there are no head-to-head trials comparing the 2 dosing regimens. Event-driven pre-exposure prophylaxis (PrEP) dosing reduces HIV conversion by 86% compared to placebo (strength of recommendation [SOR]: B, large randomized controlled trial [RCT]). Daily PrEP reduces HIV conversion by 44% to 86% (SOR: B, based on open-label RCTs).

Event-driven PrEP regimens may be associated with lower adherence when compared with daily PrEP regimens (average of 70% for event-driven PrEP vs average of 92% for daily PrEP) (SOR: B, based on open-label and cohort trials). Event-driven PrEP regimens have lower medication costs, and they are associated with no difference in the rate of sexually transmitted infections (STIs) (SOR: B, based on prospective cohort studies). Patients may prefer them to daily regimens (75% choose event-driven PrEP vs 25% choose daily PrEP) (SOR: B, based on the preponderance of prospective cohort studies with conflicting results).

References

Molina JM, Capitant C, Spire B, et al. On-demand preexposure prophylaxis in men at high risk for HIV-1 infection. NEJM. 2015;373:2237-2246.
Antoni G, Tremblay C, Delaugerre C, et al. On-demand pre-exposure prophylaxis with tenofovir disoproxil fumarate plus emtricitabine among men who have sex with men with less frequent sexual intercourse: a post-hoc analysis of the ANRS IPERGAY trial. Lancet HIV. 2020;7:e113-e120.
Grant RM, Lama JR, Anderson PL, et al. Preexposure chemoprophylaxis in men who have sex with men. NEJM. 2010;363:2587-2599.
McCormack S, Dunn DT, Desai M, et al. Preexposure prophylaxis to prevent the acquisition of HIV-1 infection (PROUD): effectiveness results from the pilot of a pragmatic open-label randomized trial. Lancet. 2016;387:53-60.
Grant RM, Mannheimer S, Hughes JP, et al. Daily and nondaily oral preexposure prophylaxis in men and transgender women who have sex with men: the Human Immunodeficiency Virus Prevention Trials Network 067/ADAPT study. Clin Infect Dis. 2018;66:1712-1721.
" class="smart-paging drupal-content" src="/sites/all/modules/contrib/smart_paging/plugins/wysiwyg/smart_paging/images/spacer.gif" title="<--pagebreak-->">Vuylsteke B, Reyniers T, De Baetselier I, et al. Daily and event-driven pre-exposure prophylaxis for men who have sex with men in Belgium: results of a prospective cohort measuring adherence, sexual behavior and STI incidence. J Intl AIDS Soc. 2019;22:e25407.
Bekker LG, Roux S, Sebastien E, et al. Daily and non-daily pre-exposure prophylaxis in African women (HPTN 067/ADAPT Cape Town Trial): a randomized, open-label, phase 2 trial. Lancet HIV. 2018;5:e68-e78.
Noret M, Balavoine S, Pintado C, et al. Daily or on-demand oral tenofovir disoproxil fumarate/emtricitabine for HIV pre-exposure prophylaxis: experience from a hospital-based clinic in France. AIDS. 2018;32:2161-2169.
Reyniers T, Nöstlinger C, Laga M, et al. Choosing between daily and event-driven pre-exposure prophylaxis: results of a Belgian PrEP demonstration project. J Acquir Immune Defic Syndr. 2018;79:186-194.
WHO. What’s the 2+1+1? Event-driven oral pre-exposure prophylaxis to prevent HIV in men who have sex with men: update to WHO’s recommendation on oral PrEP [technical brief]. Published July 2019. Accessed May 14, 2021. https://who.int/hiv/pub/prep/211/en
US Preventive Services Task Force. Prevention of human immunodeficiency virus (HIV) infection: preexposure prophylaxis [evidence summary]. Published June 11, 2019. Accessed May 14, 2021. www.uspreventiveservicestaskforce.org/uspstf/document/evidence-summary/prevention-of-human-immunodeficiency-virus-hiv-infection-pre-exposure-prophylaxis

EVIDENCE SUMMARY

Event-driven PrEP is effective for prevention of HIV transmission

An RCT evaluating the effectiveness of event-driven PrEP in 400 patients at high risk for HIV found that it reduced HIV incidence by 86% compared to placebo. Researchers recruited HIV-negative men or transgender women who had sex with men, who’d had condomless anal sex with at least 2 partners in the previous 6 months, and followed them for a median of 9.3 months for HIV acquisition.¹

Patients randomized to event-driven PrEP took tenofovir-emtricitabine (300-200 mg) on the following schedule: 2 pills 2 to 24 hours before intercourse (or 1 pill if they had taken it within the past week), followed by a third pill 24 hours later, and a fourth pill 24 hours after that. When patients had multiple consecutive episodes of intercourse, daily use was continued until 2 days after the last episode. Patients in the control group took placebo pills.¹

Event-driven PrEP reduced HIV incidence vs placebo (2 infections vs 14 infections; 0.91 vs 6.6 per 100 person-years; relative risk [RR] = 0.86; P = .002). PrEP produced more gastrointestinal (14% vs 5%; P = .002) and renal (18% vs 10%; P = .03) adverse effects than placebo. Participants took a median of 15 pills per month.¹

A post-hoc analysis of the above study, evaluating 270 patients, found that event-driven PrEP reduced HIV incidence by 100% during periods of less frequent sexual encounters. Selected participants had a median of 5 sexual encounters per month (range, 2-10), used a median of 9.5 pills per month (range, 6-13), and represented 134 person-years of follow-up. No HIV infections (0 per 100 person-years; 95% CI, 0-5; P = .013) were diagnosed in the PrEP group and 6 HIV infections (9.2 per 100 person-years; 95% CI, 3.4-20.1) were diagnosed in the placebo group, with a relative reduction of HIV incidence of 100% (95% CI, 39-100).²

For comparison, 2 large open-label trials evaluating daily PrEP found that it reduced HIV incidence by 44%³ and 86%⁴ vs placebo.

In 2019, the USPSTF published a recommendation that clinicians offer PrEP with effective antiretroviral therapy to patients at high risk for HIV acquisition.

Adherence is better with daily PrEPthan event-driven PrEP

Three prospective cohort trials evaluated PrEP adherence (extent that participants were taking PrEP at the time of sexual encounters) with different dosing regimens and found that event-driven PrEP tended to have lower adherence than daily PrEP. An open-label trial in Bangkok and Harlem (New York City) randomized 357 at-risk patients to 1 of 3 regimens: event-driven (1 tablet before and after sex), time-driven (1 tablet twice weekly with a postsex dose), and daily. Overall, patients with event-driven PrEP had lower adherence than those with daily PrEP (67% event-driven vs 97% daily; P < 0.0001).⁵

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Evidence-based answers from the Family Physicians Inquiries Network

Is event-driven PrEP dosing for HIV as effective as daily dosing?

EVIDENCE-BASED ANSWER:

References

EVIDENCE SUMMARY

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