PrEP and PEP

PrEP (pre-exposure prophylaxis)

Antiretroviral medication taken by an HIV-negative person to prevent infection. Taken as prescribed it reduces sexual HIV acquisition by about 99 percent (CDC). The efficacy figure depends almost entirely on adherence: the iPrEx trial (Grant et al., 2010, NEJM) reported 44 percent overall efficacy but found protection above 90 percent in participants with detectable drug levels, and the PROUD open-label study (McCormack et al., 2016, Lancet) recorded an 86 percent reduction in a real-world English cohort. PrEP does not prevent any other STI or pregnancy.

Daily oral PrEP (tenofovir disoproxil/emtricitabine): one tablet a day. Protective for anal sex after about 7 days, and for vaginal or frontal sex after about 21 days, because tissue drug concentrations differ between rectal and cervicovaginal tissue. This difference also means daily dosing is required for vaginal exposure — adherence tolerance is much lower.

Event-based dosing, "2-1-1": two tablets 2–24 hours before sex, one tablet 24 hours after the first dose, one more 24 hours after that. Evidence comes from IPERGAY (Molina et al., 2015, NEJM), which found an 86 percent relative reduction. It is validated for anal sex only, and is not recommended for vaginal or frontal sex, for people with hepatitis B, or in pregnancy.

Long-acting injectable cabotegravir every two months. HPTN 083 (men who have sex with men and transgender women) and HPTN 084 (cisgender women in sub-Saharan Africa) both found injectable cabotegravir superior to daily oral TDF/FTC, with HPTN 084 reporting an 89 percent further reduction in incidence. Lenacapavir, given every six months, showed very high efficacy in the PURPOSE 1 and 2 trials (2024) and is being rolled out in a growing number of countries.

Monitoring: HIV test before starting and every 3 months, hepatitis B status before starting, kidney function, and STI screening at all exposed sites. Tenofovir alafenamide is an alternative where renal or bone concerns exist. Gender-affirming hormones do not clinically reduce PrEP efficacy, and PrEP does not reduce hormone levels.

PEP (post-exposure prophylaxis)

A 28-day course of antiretrovirals started after a possible exposure. It must begin within 72 hours; effectiveness falls sharply with delay, so start within 24 hours where possible. Available from emergency departments, sexual health clinics and, in some countries, pharmacies. Do not wait for an appointment — attend an emergency department out of hours.

Situations where PEP is usually indicated: condomless receptive anal sex with a partner of unknown or positive status who is not virally suppressed; condom failure with a partner at high risk; sexual assault; needle sharing. It is generally not indicated where the source partner is on treatment with a sustained undetectable viral load, because transmission risk is effectively zero.

Baseline HIV test, then repeat testing after completing the course — most guidelines now test at 45 days from exposure with a fourth-generation assay. Side effects with modern regimens (tenofovir/emtricitabine plus an integrase inhibitor) are usually mild nausea and fatigue.

U=U

A person with HIV on effective treatment with a viral load consistently below 200 copies/mL cannot transmit HIV sexually. PARTNER2 (Rodger et al., 2019, Lancet) followed serodifferent gay male couples across roughly 76,000 acts of condomless sex with zero linked transmissions; the earlier PARTNER and Opposites Attract studies found the same. Viral suppression is HIV prevention.

What none of this does

Neither PrEP nor PEP prevents chlamydia, gonorrhoea, syphilis, herpes, HPV, mpox or hepatitis C. Doxycycline post-exposure prophylaxis (doxy-PEP) — 200 mg doxycycline within 72 hours of condomless sex — reduced bacterial STIs by roughly two-thirds in the DoxyPEP trial (Luetkemeyer et al., 2023, NEJM) among men who have sex with men and transgender women. A trial in cisgender women in Kenya (dPEP, 2023) did not show benefit, with adherence a likely factor. CDC issued guidelines in 2024 recommending it for MSM and transgender women with a bacterial STI in the past year. Antimicrobial resistance, particularly in Staphylococcus aureus and gonorrhoea, remains an open concern and is why it is targeted rather than universal.

Hepatitis A, hepatitis B, HPV and mpox are vaccine-preventable and vaccination is the appropriate protection for those.

Sources

• Grant RM et al. "Preexposure chemoprophylaxis for HIV prevention in men who have sex with men (iPrEx)." NEJM, 2010.
• McCormack S et al. "Pre-exposure prophylaxis to prevent the acquisition of HIV-1 infection (PROUD)." Lancet, 2016.
• Molina JM et al. "On-demand preexposure prophylaxis in men at high risk for HIV-1 infection (IPERGAY)." NEJM, 2015.
• Landovitz RJ et al. HPTN 083, NEJM, 2021; Delany-Moretlwe S et al. HPTN 084, Lancet, 2022.
• Bekker LG et al. PURPOSE 1 lenacapavir trial, NEJM, 2024.
• Rodger AJ et al. PARTNER2, Lancet, 2019.
• Luetkemeyer AF et al. "Postexposure doxycycline to prevent bacterial sexually transmitted infections." NEJM, 2023.
• CDC. Preexposure Prophylaxis for the Prevention of HIV Infection, 2021 update; and doxy-PEP guidelines, 2024.
• BASHH/BHIVA. UK guideline for HIV post-exposure prophylaxis following sexual exposure, current edition.

Last reviewed: August 2026.