What is PrEP, and how well does it actually prevent HIV?

PrEP — pre-exposure prophylaxis — is medicine taken by an HIV-negative person to stop the virus establishing an infection after exposure. Taken as prescribed, it is among the most effective HIV-prevention tools ever tested: the US Centers for Disease Control and Prevention put the reduction in risk of getting HIV from sex at about 99% for oral PrEP taken as prescribed, and at least 74% for HIV acquired through injection drug use [s4]. Those headline figures carry a condition that runs through all the evidence — they describe consistent, correct use, and the protection falls sharply without it.

What the trials measured

The first proof came from the iPrEx trial, which randomly assigned 2,499 HIV-negative men and transgender women who have sex with men to a daily pill combining emtricitabine and tenofovir (FTC-TDF) or placebo [s1]. Over the study, 100 participants became infected — 36 in the FTC-TDF group and 64 on placebo — a 44% reduction in HIV incidence (95% CI 15 to 63) [s1]. That number looks modest next to the CDC's 99%, and the gap is the point: many participants did not take the drug reliably, and the protective effect tracked closely with whether the medicine could actually be detected in the blood [s1].

Partners PrEP tested the same question in heterosexual couples. It enrolled 4,758 couples in Kenya and Uganda in which one partner had HIV-1 and the other did not, assigning the HIV-negative partner to daily tenofovir, tenofovir-emtricitabine, or placebo [s3]. There were 82 infections: 17 with tenofovir (0.65 per 100 person-years), 13 with the two-drug combination (0.50 per 100 person-years) and 52 on placebo (1.99 per 100 person-years) — reductions of 67% and 75% respectively [s3].

Adherence is the variable that matters

The clearest demonstration that adherence, not the drug, sets the ceiling came from PROUD, an open-label trial in 13 English sexual-health clinics that gave PrEP to gay and bisexual men either immediately or after a one-year deferral [s2]. Three infections occurred in the immediate group against 20 in the deferred group — 1.2 versus 9.0 per 100 person-years, a relative reduction of 86% (90% CI 64 to 96) [s2]. The trial calculated that 13 men would need access to a year of PrEP to prevent one HIV infection [s2].

A 2016 systematic review and meta-analysis of 18 studies drew the threads together. Across trials in which more than 70% of participants took PrEP, the pooled risk of HIV acquisition fell by 70% compared with placebo (risk ratio 0.30, 95% CI 0.21 to 0.45); trials with low uptake showed no significant protection [s5]. That is the mechanism behind the CDC's near-total effectiveness figure: the ceiling is high, but only reliable use reaches it.

What it does and does not cover

PrEP protects against HIV and nothing else. It does not prevent other sexually transmitted infections or pregnancy, which is why guidelines pair it with condoms and regular STI screening [s4]. Reassuringly, the same review found no consistent evidence that starting PrEP led people to take more sexual risks, and no rise in pregnancy-related harms [s5].

Safety in the trials was reassuring too. Serious adverse events were no more common with PrEP than placebo; the most frequent complaints were early, transient nausea and headache [s1] [s2]. PrEP is not for someone who already has HIV — starting it during an undetected acute infection is the main route to drug resistance, which is why testing before and during use is built into every protocol [s4].

The format has also widened since these trials. Injectable cabotegravir, given as a scheduled injection rather than a daily pill, is over 99% effective at preventing HIV from sex when doses are kept on schedule, removing the daily-adherence problem that limited the early oral results [s4].

The bottom line

The evidence supports a specific claim, not a slogan. Oral PrEP can cut the risk of sexually acquired HIV by around 99% [s4], but the randomised trials that followed real people ranged from 44% to 86% because real people miss doses [s1] [s2]. PrEP works to the extent it is taken, protects against HIV alone, and belongs alongside — not instead of — condoms, testing and treatment of partners living with HIV.

This article is informational and is not medical advice. Anyone considering PrEP should discuss suitability, testing and follow-up with a clinician.

Sources

• Preexposure Chemoprophylaxis for HIV Prevention in Men Who Have Sex with Men — New England Journal of Medicine, 2010-12-30
• Pre-exposure prophylaxis to prevent the acquisition of HIV-1 infection (PROUD) — The Lancet, 2016-01-02
• Antiretroviral Prophylaxis for HIV Prevention in Heterosexual Men and Women — New England Journal of Medicine, 2012-08-02
• Prescribe HIV Prevention: PrEP — Centers for Disease Control and Prevention
• Effectiveness and safety of oral HIV preexposure prophylaxis for all populations — AIDS, 2016-07-31