HIV post-exposure and pre-exposure prophylaxis

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Post-exposure prophylaxis uses a short three-drug antiretroviral course after a discrete exposure to prevent systemic infection before viral reservoirs become established. Benefit depends on prompt initiation, adherence and completion.

Pre-exposure prophylaxis uses two active antiretrovirals before and after ongoing exposure. It is highly effective when taken correctly and should be offered through an individualized conversation about sexual or injecting risk, preferences and access.

Both pathways require excluding established or acute HIV. Two-drug PrEP in undiagnosed infection can select resistance, while PEP given after the 72-hour window offers no established benefit and should transition to testing and prevention planning.

Tenofovir and emtricitabine also suppress hepatitis B. Starting and stopping them in chronic HBV requires a deliberate plan because viral rebound can cause hepatitis. PrEP does not prevent other STIs or pregnancy.

Key points

PEP is an emergency: start ideally within 24 hours and no later than 72 hours after a substantial exposure.
Assess fluid, route, mucosal or percutaneous injury, source viral load and treatment, prevalence and modifying factors without using stigmatizing identity assumptions.
Take baseline fourth-generation HIV, renal, liver, hepatitis B and C, pregnancy and STI tests, but do not delay the first PEP dose.
A standard UK PEP course is tenofovir disoproxil 245 mg plus emtricitabine 200 mg once daily with raltegravir 1200 mg once daily for 28 days.
Provide the complete 28-day supply or a reliable rapid completion route, interaction advice and an early adherence check.
PrEP is started only after HIV-negative status and acute infection have been adequately excluded.
The 2025 UK guidance offers event-based dosing to all PrEP users: use a two-day post-risk tail for anal or insertive sex and seven days for receptive vaginal, neovaginal or injecting exposure.
PrEP care includes repeat HIV and STI testing, renal monitoring, hepatitis B continuity, adherence and vaccination review.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Sexual mucosal exposure

Infected genital or rectal fluid contacts susceptible mucosa, with risk shaped by route, trauma and source viraemia.

Percutaneous blood exposure

A contaminated hollow-bore needle or shared injection equipment introduces infected blood directly into tissue or circulation.

Occupational splash exposure

Blood contacting eye, mouth or damaged skin may justify assessment, while intact-skin exposure does not transmit HIV.

Ongoing network exposure

Repeated exposures arise from partner viraemia, changing partners, condom preference, injecting practice and barriers to prevention access.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Local viral establishment
Founder virus infects susceptible mucosal CD4 cells and begins expansion before systemic reservoirs are fully established.
2
Reverse-transcriptase interruption
Intracellular tenofovir and emtricitabine metabolites terminate viral DNA synthesis, preventing productive infection when adequate drug concentrations surround the exposure.
3
Integration blockade
Raltegravir blocks insertion of newly made viral DNA into host chromosomes, adding a distinct barrier during the time-critical post-exposure course.
4
Pre-exposure drug saturation
Consistent PrEP establishes active metabolites in target tissues before exposure and blocks productive infection after viral entry.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Sexual mucosal exposureRed flag

Condomless receptive anal or vaginal exposure to a source with transmissible HIV may warrant PEP according to viral load and context.

Occupational sharps injuryRed flag

A hollow-bore injury contaminated with blood carries greater risk than intact-skin contact and triggers immediate occupational assessment.

Needle-sharing exposureRed flag

Shared injection equipment containing fresh blood can transmit HIV and requires PEP, hepatitis and harm-reduction review.

Negligible-risk contact

Saliva on intact skin, social contact and exposure to a durably undetectable sexual source do not indicate PEP.

Ongoing PrEP need

Repeated condomless exposure, recent bacterial STI, repeated PEP use or a partner with non-suppressed HIV supports PrEP discussion.

Possible acute HIVRed flag

Fever, rash, sore throat, nodes or diarrhoea after recent risk requires RNA testing before a PrEP-only regimen.

Red flags requiring action

Exposure approaching 72 hours needs immediate prescribing rather than referral delay.
Fever, rash, pharyngitis or lymphadenopathy before PEP or PrEP raises acute HIV and requires HIV RNA assessment.
A reactive or indeterminate baseline HIV test means PrEP must not be used as an incomplete treatment regimen.
Known hepatitis B complicates stopping tenofovir and emtricitabine and requires liver and HBV planning.
Pregnancy or breastfeeding never justifies automatic denial of indicated PEP, but needs urgent specialist prescribing review.
Sexual assault requires trauma-informed care, emergency contraception, hepatitis B prevention, STI prophylaxis decisions, safeguarding and forensic options alongside HIV care.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
Baseline fourth-generation HIV testFirst step
Why
Exclude established infection before PEP or PrEP and provide a comparison for follow-up.
Interpretation and limitations
A negative result does not exclude very recent acquisition; exposure timing, symptoms and previous PrEP or PEP determine need for HIV RNA.
02
HIV RNA
Why
Detect acute infection when symptoms, recent exposure or recent antiretroviral prevention may delay serological clarity.
Interpretation and limitations
Do not start two-drug PrEP alone while acute infection is being resolved; obtain urgent HIV specialist input.
03
Source HIV and viral-load information
Why
Refine PEP need when the source can consent to testing or reliable records exist.
Interpretation and limitations
Do not delay PEP while obtaining source results; sustained documented undetectable viral load means no sexual transmission risk.
04
Creatinine and eGFR
Why
Assess safe tenofovir disoproxil use and establish a PrEP renal baseline.
Interpretation and limitations
A result can follow the first emergency PEP dose in a clearly eligible exposure, but significant renal disease needs specialist modification.
05
Hepatitis B serology
Why
Identify susceptibility requiring vaccination and chronic infection affected by tenofovir or emtricitabine withdrawal.
Interpretation and limitations
HBsAg, anti-HBc and anti-HBs guide vaccination and stopping plans; chronic HBV requires continued treatment or close flare monitoring.
06
Hepatitis C, STI and pregnancy tests
Why
Address infections and reproductive consequences sharing the exposure.
Interpretation and limitations
Test each exposed site and repeat blood tests after window periods; pregnancy informs choice but does not automatically preclude PEP or PrEP.
07
Medication interaction review
Why
Protect raltegravir absorption and identify nephrotoxic or interacting treatment.
Interpretation and limitations
Polyvalent cation antacids and supplements require timing advice; check all medicines with a current HIV interaction resource.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

No-risk contact

Saliva, sweat, tears, social contact and blood on intact skin do not create a clinically significant HIV exposure.

Acute HIV infection

Fever, rash and pharyngitis after recent risk may represent HIV already established before prophylaxis; urgent antigen-antibody and RNA testing is required.

Other blood-borne virus exposure

Hepatitis B and C share some exposures but require separate baseline testing, hepatitis B vaccination or immunoglobulin decisions, and virus-specific follow-up.

Bacterial STI

Chlamydia, gonorrhoea and syphilis share sexual exposures but need anatomical-site testing, organism-specific treatment and appropriate partner notification independent of HIV prophylaxis.

Medication adverse effect

Nausea, headache or renal change during prophylaxis may reflect medicine toxicity or intercurrent illness; prompt review helps preserve safe course completion.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01NOWStart eligible PEP immediatelyFirst stepA substantial exposure occurred within the preceding 72 hours.

1Establish exact time, fluid, route, injury, source HIV status and viral suppression and whether the exposure was consensual.
2Take baseline HIV, renal, liver, hepatitis, pregnancy and site-specific STI specimens without delaying the first dose.
3Give tenofovir disoproxil and emtricitabine plus raltegravir immediately and provide access to the full 28-day course.
4Arrange early specialist or sexual-health review for adherence, results, side effects, safeguarding and ongoing prevention.

02REVIEWComplete and follow PEPThe first PEP dose has been taken.

1Check missed doses, nausea, medication supply, cation interactions and renal or liver results within the first days.
2Modify only with specialist advice for renal impairment, resistance, pregnancy, hepatitis B or an interacting source regimen.
3Complete 28 days and perform follow-up fourth-generation HIV testing at the national guideline interval after completion.
4Repeat hepatitis C and STI tests as indicated and transition recurrent risk directly to PrEP without an unprotected gap.

03START PREPEstablish HIV-negative PrEP eligibilityOngoing or anticipated exposure makes PrEP beneficial.

1Confirm a negative fourth-generation test and request HIV RNA if acute symptoms, very recent risk or recent PEP or PrEP creates uncertainty.
2Check eGFR, hepatitis B status, pregnancy, medications and STI screen and offer hepatitis A or B vaccination where indicated.
3Choose daily tenofovir disoproxil and emtricitabine for broad exposure coverage and explain lead-in and stopping doses.
4Use a double dose 2 to 24 hours before planned risk, then select the two-day or seven-day post-exposure dosing tail from the anatomical exposure.

04MAINTAINKeep PrEP effectivePrEP has started and exposure continues or may recur.

1Repeat HIV testing at least every three months and never renew across symptoms of acute infection without assessment.
2Monitor renal function at the age- and risk-based interval and reassess interacting or nephrotoxic medicines.
3Perform frequent site-specific STI screening, vaccination and reproductive-health care without making continued PrEP conditional on an STI-free result.
4Review adherence, exposure pattern and whether daily, event-based, continuation or safe stopping best matches current needs.

Key medicines and prescribing safety4 treatments · regimens, roles and cautions

Blocks reverse transcription alongside a third active agent during the post-exposure establishment period.

Tenofovir disoproxil and emtricitabine for PEP

Give one tablet containing tenofovir disoproxil 245 mg and emtricitabine 200 mg orally once daily for 28 days as the PEP backbone.

Check renal and hepatitis B status, avoid unreviewed nephrotoxins and do not stop chronic HBV-active therapy without a liver plan.

Adds rapid integrase inhibition and completes the three-drug prophylactic course.

Raltegravir for PEP

Give 1200 mg orally once daily for 28 days with tenofovir disoproxil and emtricitabine under the current UK PEP regimen.

Check formulation, separate from polyvalent cation antacids as advised, review pregnancy and interactions, and avoid missed doses.

Maintains protective drug concentrations for ongoing sexual or injecting exposure.

Daily oral PrEP

Give tenofovir disoproxil 245 mg and emtricitabine 200 mg as one tablet orally once daily after HIV-negative status is established.

Monitor HIV and renal function, assess hepatitis B before stopping and investigate acute-HIV symptoms immediately to prevent resistance.

Provides the 2025 UK event-based option for all PrEP users when exposure can be anticipated and the correct post-risk tail is followed.

Quick-start event-based oral PrEP

Take two tenofovir and emtricitabine tablets 2 to 24 hours before risk; continue one daily for two days after the last anal or insertive-sex risk, or for seven days after receptive vaginal, neovaginal or injecting risk.

Not a substitute for three-drug PEP after an unprotected past exposure; extend the daily tail if exposure continues and obtain specialist advice before intermittent use with chronic hepatitis B.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Breakthrough HIV infection

Late initiation, missed doses, ongoing exposure or resistant virus permits acquisition and requires immediate full treatment.

Drug resistance

Two-drug PrEP during undiagnosed HIV or an incomplete PEP course can select emtricitabine or tenofovir resistance and complicate initial treatment.

Renal toxicity

Tenofovir disoproxil can impair proximal tubular function, particularly with baseline kidney disease, older age or concurrent nephrotoxic medicines.

Hepatitis B flare

Stopping tenofovir-emtricitabine in chronic hepatitis B can permit rebound HBV replication and clinically important hepatitis, so cessation needs planned monitoring.

Missed prevention opportunity

Failure to transition repeated exposures to PrEP, source treatment and broader sexual health permits avoidable future risk.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Confirm the PEP start time, completion of 28 days and any interruption or vomiting affecting exposure.
Review baseline and follow-up HIV results personally and investigate acute symptoms with RNA rather than issuing routine PrEP.
Monitor creatinine and eGFR during prolonged PrEP and earlier with age, renal disease or nephrotoxic medicines.
Track hepatitis B vaccination, chronic HBV treatment and liver tests when tenofovir or emtricitabine is stopped.
Offer site-specific chlamydia and gonorrhoea, syphilis and hepatitis C testing at risk-based intervals.
Review pregnancy intention, contraception and breastfeeding with a specialist prevention plan.
Document ongoing consent, sexual wellbeing, safeguarding, adherence preference and access to emergency PEP.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

The clock starts at exposure

Referral and source testing do not pause biological establishment, so the first PEP dose precedes administrative completion.

Undetectable means no sexual risk

A source with reliably sustained viral suppression does not transmit HIV sexually and does not create a PEP indication.

Baseline negative is not future negative

PEP protects one event and PrEP protects while taken; scheduled follow-up is required to detect pre-existing window infection.

Two drugs can select resistance

Starting PrEP during unrecognised acute HIV exposes replicating virus to an incomplete treatment combination.

HBV makes stopping clinical

Tenofovir and emtricitabine suppress HBV, so cessation can trigger viral rebound even when they were prescribed for HIV prevention.

Repeated PEP signals prevention need

Multiple emergency courses are an opportunity to offer PrEP, vaccination, condoms and non-judgmental risk support.

11Common pitfallsFrequent interpretation and management errors.

01
Do not delay PEP while waiting for source testing or a specialist appointment.
02
Do not start PEP after 72 hours as if efficacy were established.
03
Do not prescribe PrEP before excluding acute HIV when symptoms or timing raise concern.
04
Do not use the two-day 2:1:1 tail after receptive vaginal, neovaginal or injecting exposure, which requires seven post-risk daily doses.
05
Do not stop tenofovir and emtricitabine in chronic hepatitis B without a plan.
06
Do not provide only a starter pack without a reliable route to complete 28 days.