HIV prevention: pre-exposure and post-exposure prophylaxis

• HIV pre-exposure prophylaxis (PrEP) is antiretroviral medicine taken before possible exposure. It is about 99% effective at preventing sexual HIV when taken as prescribed, and at least 74% effective at preventing HIV from injection drug use. ^[3]
• HIV post-exposure prophylaxis (PEP) is a 28-day course of antiretroviral medicine started after a substantial exposure. It works best when the first dose is taken within a few hours; it can be started up to 72 hours after exposure. ^[1][6]
• Three approved (or recommended) PrEP strategies exist: daily oral emtricitabine/tenofovir disoproxil fumarate (F/TDF), daily oral emtricitabine/tenofovir alafenamide (F/TAF), and an injectable given every 2 months (cabotegravir). A fourth, lenacapavir injected every 6 months, is now an option for people weighing at least 77 lb (35 kg). ^[2][3]
• If viral load is kept below 200 copies/mL with treatment, HIV is not transmitted sexually. This is the meaning of undetectable equals untransmittable (U=U). ^[4]
• Prevention fails in practice when HIV testing is not repeated, when PrEP monitoring is skipped, and when PEP is started too late. Test, treat, and taper (tail) follow-up as local guidance demands. ^[1][3]
• This page complements the MedGrasp topics HIV infection and AIDS and Paediatric HIV and PMTCT, which cover mother-to-child prevention in full.

By the end of this page you should be able to:

1. Explain the biology behind PrEP and PEP in one or two sentences.
2. Name the three first-line PrEP formulations, their dosing, and their onsets of protection, and explain why F/TAF is not yet recommended for receptive vaginal sex.
3. Decide when event-driven (2-1-1) oral PrEP is appropriate and when it is not. ^[3]
4. Plan the correct HIV testing and safety monitoring for a person starting and continuing PrEP.
5. Recognise the exposures that warrant PEP, start the right regimen quickly, and prevent loss to follow-up during the 28-day course.
6. Explain U=U precisely, including the viral load threshold and its limits.
7. Contrast occupational and non-occupational PEP management and describe the immediate steps in each.
8. Apply the main differences between US (CDC), WHO, UK (BHIVA/BASHH), and European (EACS) practice.

"Pre-exposure" and "post-exposure" describe timing relative to the potential exposure, not the person: PrEP is for people who are HIV-negative and at substantial risk; PEP is for anyone (HIV-negative) after a substantial exposure. Neither replaces condoms or other risk reduction, and neither protects against other infections.

The burden that argues for broad access to PrEP and PEP is large: around 39,000 people received an HIV diagnosis in the United States in 2023, and over one million people became infected with HIV worldwide in 2022. ^{[1][2] [6]}

Appropriate candidates are those whose behaviour and epidemiological context place them at substantive risk of acquiring HIV. In routine practice these include: people with a sexual partner living with HIV without sustained viral suppression; gay, bisexual and other men who have sex with men; transgender and gender-diverse people; heterosexual people with multiple partners whose HIV status is unknown; people who share injecting equipment; people diagnosed with a bacterial sexually transmitted infection (STI); people who have been incarcerated; people who engage in transactional sex; and people who ask for PrEP. PrEP should be offered as part of a comprehensive prevention plan with condoms, STI screening, and harm-reduction support. ^[1][3]

These per-act estimates come from the 2025 CDC non-occupational PEP guidelines and are the numbers clinicians use to judge "substantial risk". They are per 10,000 exposures; the upper values reflect a real exposure and the conditions around it (viral load, fluid, mucosa). ^[1]

Receptive oral intercourse is classified as "low" risk. Saliva, urine, sweat, tears and intact skin are not infectious routes unless visibly bloody. For a percutaneous needle-stick the same 2025 table gives 23 per 10,000 exposures, or about 0.23%. ^[1]

The direct evidence is now strong enough to be medical consensus. The HPTN 052 trial reported 96% reduction in transmission with early ART, with no linked transmissions once the partner with HIV had a suppressed viral load; the PARTNER, PARTNER2 and Opposites Attract studies together recorded no genetically linked infections while the partner with HIV stayed virally suppressed, across more than 125,000 sex acts without a condom and without PrEP. Most participants in PARTNER had fewer than 50 copies/mL. Transmission risk estimates in those cohorts were zero events, with upper 95% confidence limits below 0.30 per 100 couple-years for sex overall. ^[4]

Limits to state honestly:

• U=U covers sexual transmission, not transmission to a child in pregnancy or breastfeeding (there, HIV medicines reduce risk to under 1%, but the risk is not zero) and not syringe sharing (unknown, likely reduced). ^[4]
• Suppression must be sustained; risk returns when ART stops. ^[4]
• U=U is a message about the partner with HIV's viral load. It does not replace condoms for other STIs or for anal STI risk. ^[4]

PrEP is antiretroviral medicine taken before potential exposure. Correct use reduces sexual acquisition by about 99% and acquisition from injection drug use by at least 74%; in people who have difficulty adhering daily, injectable PrEP given every 2 months is over 99% effective against sexual transmission. ^[3]

Before starting any PrEP, confirm that the person is HIV-negative and does not have acute HIV infection. Use blood tests, not oral swabs: combination antigen/antibody testing plus HIV-1 RNA testing, with follow-up testing in ambiguous cases. Ask specifically about fever, sore throat, rash, lymphadenopathy or influenza-like symptoms in the month before testing; if present, defer PrEP until results settle. ^[3]

Baseline assessments when starting oral PrEP:

• Kidney function with a calculated creatinine clearance. F/TDF needs 60 or above mL/min; F/TAF needs 30 or above mL/min. ^[3]
• Hepatitis B serology for everyone starting an oral tenofovir-containing regimen; these drugs treat active hepatitis B, and stopping them can trigger hepatic flare. ^[3]
• Screening for chlamydia, gonorrhoea and syphilis in all sexually active adults. ^[3]
• Lipids and a baseline weight for F/TAF. ^[3]
• For CAB: no renal testing is needed; renal monitoring continues for oral options only. ^[3]

PrEP is safe in pregnancy. Two regimens are recommended: oral F/TDF, which is generally safe during pregnancy and breastfeeding, and injectable cabotegravir, for which published pregnancy data are sparse and the decision should be shared. F/TAF is not yet studied for receptive vaginal HIV prevention. ^[3]

The 2-1-1 schedule is off-label dosing of F/TDF for adult gay and bisexual men: two pills 2 to 24 hours before sex, one pill 24 hours after the first two-pill dose, and one pill 48 hours after it. ^[3]

The BHIVA/BASHH 2025 guidelines move in the opposite direction: they offer quick-start double-dose oral PrEP for everybody and event-based dosing for a wider range of people, including new use in pregnancy and other populations where the evidence is weaker. Where guidelines differ, discuss the strongest option and the one the patient can adhere to. ^[7]

Cabotegravir is given as an intramuscular injection: the first injection, the second 1 month later, then one every 2 months. A 4-week oral lead-in (30 mg daily) is optional for patients worried about side effects or to test tolerability. Counsel patients that injections must be kept on schedule; HIV infections in trials happened when people delayed injections for several months. ^[3]

Lenacapavir is subcutaneous (two 1.5 mL injections into the abdomen, at least 4 inches apart) every 6 months, after a two-day oral load. Efficacy in the two pivotal trials was 100% (PURPOSE 1) and 96% (PURPOSE 2) against background HIV incidence over 52 weeks. Injection-site reactions were common (68.8% and 83.2%) but mainly mild to moderate, and few people stopped because of them. Lenacapavir may be used in pregnancy or continued in women who become pregnant, with shared decision-making. When stopping, levels decline over 18 months and protection ends after 6 months: offer an oral method before that. Oral bridging at 300 mg weekly is available for a missed maintenance injection anticipated to be 14 or more days late, starting 6 months after the last injection. ^{[2] [4]}

Notable details:

• Daily oral PrEP reaches protective levels around 7 days for receptive anal sex and up to 21 days (sometimes earlier in cervicovaginal tissue) for receptive vaginal sex and injection drug use. ^[3]
• Stopping daily oral PrEP leaves protection declining over 7 to 10 days. ^[3]
• Current surveillance shows only 63% of people with diagnosed HIV have sustained viral suppression, which is why U=U messaging and PrEP monitoring both matter. ^[4]

PEP means starting a full 28-day antiretroviral course as soon as possible after a substantial exposure, to abort local replication before it becomes systemic. It works only within a narrow window. Animal data and human experience support a 72-hour outer limit, with the first hours carrying far more benefit than the later hours; its effectiveness has never been tested in a randomized trial because a placebo-controlled trial would be unethical. ^[1]

WHO's 2024 PEP guidelines prioritise access (community delivery, task sharing) and state the same timing: ideally within 24 hours and no later than 72 hours, with a 28-day course; an effective minimum of two or three drugs. ^[6]

A substantial exposure means non-intact skin or mucous membrane contact with body fluids that can transmit HIV, in a context where the source may be a person with HIV and without sustained viral suppression, or that status is unknown. Topical and surface contact (saliva, urine, sweat, tears) without blood does not warrant PEP. ^[1]

CDC 2025 (non-occupational PEP) is the reference to follow when sexual exposure, drug injection, or any other non-occupational exposure has occurred. Its instruction is: start as soon as possible, ideally within 24 hours and certainly within 72 hours; do not delay the first dose while waiting for any laboratory result; provide a 28-day course; prefer a three-drug regimen. ^[1]

Preferred regimens for most adults and adolescents (2025 CDC nPEP) are either one fixed-dose tablet of bictegravir/emtricitabine/tenofovir alafenamide, once daily, or dolutegravir plus a tenofovir backbone (TAF or TDF, plus emtricitabine or lamivudine). ^[1]

Occupational exposures (needle stick, sharps, body-fluid splash) are managed under US public-health guidance, distinct from non-occupational PEP, though the medication regimens and the 72-hour limit are essentially the same. Any exposure from a patient with HIV (or unknown status) should have the source documented, source HIV testing sought, and a three-drug 28-day course started promptly. Follow the latest institutional and national occupational PEP pathway; the USPHS 2013 document still shapes many institutional protocols, and CDC's 2025 nPEP document directs readers to the separate occupational guidelines and the NCCC. ^[1]

Routine monitoring of creatinine, AST and ALT is not necessary during the 28 days unless baseline values are abnormal or symptoms suggest liver or kidney injury. ^[1]

• Time to maximum protection with daily oral F/TDF: about 7 days for receptive anal sex; up to 21 days for receptive vaginal sex and injection drug use (with earlier cervicovaginal protection possible). ^{[1] [3]}
• After stopping oral PrEP, protection wanes over 7 to 10 days. ^[3]
• For a person on oral PrEP whose partner has HIV, the viral load stays under 200 copies/mL in the source, and transmission does not occur. ^[1][4]

Testing is the single most common point of failure. The strategy is:

1. Test for HIV before and during: always use laboratory blood assays, not oral swabs, for PrEP decisions. Combination Ag/Ab plus RNA testing when indicated (early symptoms or recent exposure). ^[3]
2. Repeat at least every 3 months for daily PrEP, or at every 2 months for injectable cabotegravir. ^[3]
3. For PEP, test at baseline, 4-6 weeks and 12 weeks, with diagnostic RNA included. ^[1]
4. Test for STIs routinely: chlamydia/gonorrhoea/syphilis for all sexually active adults before PrEP; syphilis and gonorrhoea at follow-up every 3 months for sexually active PrEP users; chlamydia every 6 months for heterosexual users and every 4 months for gay and bisexual men on injectable PrEP. ^[3]
5. Renal function: eCrCl at baseline and at least annually on oral PrEP; every 6 months if the patient is 50 or older or has a baseline eCrCl under 90 mL/min; more often with hypertension or diabetes. Do not withhold PrEP if eCrCl remains 60 or above mL/min (F/TDF) or 30 or above mL/min (F/TAF). ^[3]
6. Hepatitis B: screen everyone starting oral PrEP. ^[3]
7. Lipids and weight for F/TAF, every 12 months. ^[3]
8. Pregnancy: two regimens recommended (F/TDF, or CAB with shared decision-making). ^[3]

• Adolescents: PrEP approved for those 35 kg or heavier; F/TDF and F/TAF (not CAB, pending study). Bone monitoring changes in younger adolescents using F/TDF more than F/TAF. ^[3]
• People with kidney disease: reduce or avoid oral F/TDF; F/TAF can be used at eCrCl 30 or above; CAB requires no renal assessment for eCrCl under 30. ^[3]
• People who inject drugs: offer PrEP (at least 74% effective oral); combine with harm reduction. ^[3]
• People with active hepatitis B: use F/TDF/F/TAF for treatment and avoid episodic dosing; 2-1-1 dosing is contraindicated. ^[3]
• Pregnancy and breastfeeding: F/TDF (preferred, with evidence), CAB (shared decision). ^[3]
• Sexual assault: PEP offered as part of post-assault services; trauma-informed care, forensic examination and support services, low completion rates need protocol and follow-up support. ^[1]
• Children after exposure: refer to paediatric pathways and national PEP-in-children guidance; doses and drug choices differ. ^[1]

PrEP and PEP must still be the standard of care where resources are limited. Simplify to a single daily F/TDF pill and the fewest possible tests; avoid unnecessary repeat creatinine testing during PEP when baseline results are normal. Use task sharing and community delivery for PEP so people can start within 24 hours. Use rapid point-of-care HIV tests, treat bacterial STIs and pregnancy, and support adherence with simple regimens. Where viral load testing is unavailable, follow clinical and CD4-based staging and refer for specialist care. ^[5][6]

• PrEP is the best current way to prevent HIV in a susceptible person: oral daily F/TDF (99% effective sexually, 74% or more for IDU) or F/TAF (sexual only); CAB injectable every 2 months; lenacapavir every 6 months for eligible candidates. ^[2][3]
• PrEP only works if taken as prescribed: daily protection onset is about 7 days (anal) or up to 21 days (vaginal/IDU); injectables need on-time dosing. ^[3]
• Testing is mandatory and repeated: before PrEP, then at least every 3 months (2 months for CAB); renal monitoring annually and every 6 months for higher-risk kidney patients; lipids for F/TAF. ^[3]
• Event-driven (2-1-1) PrEP is off-label, only for adult gay and bisexual men, and never in active HBV infection. ^[3]
• PEP is a 28-day, three-drug regimen, started within hours and no later than 72 hours after exposure, with a follow-up test at 4-6 weeks and 12 weeks. ^[1][6]
• Occupational and non-occupational PEP share regimens and timing; first dose before any result. ^[1]
• If a partner's HIV viral load stays below 200 copies/mL, sexual transmission does not occur (U=U). ^[4]
• U=U leaves zero risk for sexual transmission; pregnancy/feeding transmission is not zero, though it is under 1% with suppression and infant prophylaxis. ^[4]
• Success depends on access and repeat testing, not on any single medicine. ^[1][3]

Read first: HIV infection and AIDS; Read next: Paediatric HIV and PMTCT. Also relevant: tuberculosis in the immunocompromised host; opportunistic infection prophylaxis; STI screening algorithms.