If 40% of U.S. men who have sex with men (MSM) began pre-exposure prophylaxis (PrEP) according to Centers for Disease Control and Prevention (CDC) guidelines and 62% had good PrEP adherence, one-third of expected HIV infections would be prevented over the next decade, a modeling study predicts. In this scenario, 25 MSM would have to use PrEP to prevent one infection.
In randomized controlled trials, PrEP proved effective in preventing HIV infection in MSM, heterosexual women and men, and injection drug users. How well PrEP works in populations outside trials, the CDC researchers note, will depend on clinical indications for PrEP in the region, how many at-risk people adopt PrEP and how well they adhere to the PrEP regimen. The only licensed PrEP regimen today is once-daily oral tenofovir/emtricitabine (Truvada).
The CDC supports daily PrEP as part of comprehensive HIV prevention and has issued guidelines for PrEP use. To get a better understanding of the epidemiologic impact of PrEP (percentage of infections averted) and PrEP efficiency (number needed to treat), the CDC team conducted this mathematical modeling analysis.
To estimate PrEP impact, the investigators used a network-based mathematical model
of HIV transmission dynamics. The model considered an open population of U.S. MSM who might have three types of partners: main partners, short-term casual partners with repeated contacts and one-time partners. The analysis used the behavioral conditions in the CDC guidelines (all involving anal intercourse with possibly HIV-positive partners) to simulate PrEP eligibility.
In the model's base scenario, 40% of MSM start PrEP, and that proportion varied from 10% to 90% in sensitivity analyses. The model based PrEP adherence on a U.S. PrEP demonstration project in which varying proportions of men took no doses weekly (21%), one dose weekly (7%), two to three doses weekly (10%) or four or more doses weekly (62%). Those four adherence levels resulted in reductions in per-act HIV acquisition risk of 0%, 31%, 81% and 95%, respectively. The model set HIV prevalence in the MSM population at 26%. An online tool provides further model details and allows users to simulate outcomes according to percentage of PrEP coverage and proportion of highly adherent men.
With 40% MSM PrEP uptake and 62% of those highly adherent to PrEP, percentage of infections averted over the next 10 years ranged from 26% to 33% in three joint HIV risk conditions analyzed, all involving anal intercourse. The 33% of infections avoided represent 1162 new infections per 100,000 person-years at risk. Number needed to treat to prevent one HIV infection in the three HIV risk conditions ranged from 22 to 25 men.
When the model varied PrEP uptake from 10% to 90% (with 62% highly adherent), percentage of infections averted in the next 10 years ranged from 10.8% to 49.7%, and number needed to treat ranged from 26 to 27. When the model varied PrEP adherence from 10% to 90% (with 40% uptake), percentage of infections avoided ranged from 17.4% to 40.2%, and number needed to treat ranged from 48 to 20.
Percentage of infections averted grew over the decade considered through the direct prophylactic benefits of PrEP by current users and by an indirect benefit to the MSM community as HIV prevalence fell. The model also projected that increasing HIV testing frequency from every six months to every 12 months had a minimal impact on percentage of infections averted, raising the percentage from 33% to 36%.
The CDC investigators believe their findings show that following the CDC PrEP guidelines "would result in significant and sustained declines in HIV prevalence and incidence among MSM in the United States[.]" They propose that the guidelines "strike a good balance between epidemiologic impact [percentage of infections averted] and efficiency [number needed to treat] at plausible scale-up levels." Better adherence counseling, they suggest, could improve number needed to treat.
Mark Mascolini writes about HIV infection.