HIV pre-exposure prophylaxis

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

Pre-exposure prophylaxis maintains antiretroviral activity in susceptible tissues before and after HIV exposure. Oral tenofovir disoproxil with emtricitabine is highly effective when taken with the correct lead-in, continuity and post-risk tail. Access should follow an individual conversation about anticipated exposure, preferences and barriers rather than narrow identity or trial-derived categories.

The first safety question is whether HIV is already present. A negative test inside the window, acute retroviral symptoms or recent antiretroviral use can conceal early infection. Two drugs are inadequate treatment and can select resistance, so uncertain cases require laboratory antigen-antibody testing, HIV RNA and specialist advice before routine PrEP starts.

Dosing depends on anatomy and timing. The 2025 BHIVA/BASHH guideline supports a two-tablet quick start before risk and event-based options for all users, with different continuation tails: two daily doses after the last anal or insertive exposure and seven daily doses after receptive vaginal, neovaginal or injecting exposure. Continued exposure extends the daily course.

Tenofovir disoproxil can affect kidney function, while both tenofovir and emtricitabine suppress hepatitis B. Baseline eGFR and HBV serology therefore serve different purposes: renal results determine medicine safety, and HBV status determines whether intermittent use or stopping could trigger viral rebound.

PrEP visits are prevention care rather than a test of behaviour. Repeat HIV and site-specific STI testing, vaccination, reproductive care, medication review and adherence support should make PrEP safer and easier to use. An STI diagnosis prompts treatment and partner notification but does not automatically end PrEP.

Key points

PrEP is for HIV-negative people who may benefit from protection before future sexual or injecting exposure; eligibility should be individualised and equitable.
Confirm a laboratory HIV-negative result and use HIV RNA when acute symptoms, very recent risk or recent PEP or PrEP makes serology uncertain.
Check renal function, hepatitis B status, pregnancy, medicines and site-specific STIs before oral tenofovir disoproxil with emtricitabine.
The 2025 UK guideline uses a double-dose quick start 2 to 24 hours before anticipated risk for event-based oral PrEP.
Continue daily doses for two days after the last anal or insertive-sex exposure, but for seven days after the last receptive vaginal, neovaginal or injecting exposure.
Daily dosing is simpler for frequent or unpredictable exposure; event-based dosing requires anticipation and correct anatomical tail.
Repeat HIV testing at least every three months, monitor renal function by age and risk, and test STIs at exposed sites.
PrEP does not prevent other STIs or pregnancy, and stopping in chronic HBV requires an HBV treatment or flare-monitoring plan.

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

Anticipated sexual exposure

HIV-containing genital or rectal fluid may reach susceptible mucosa during future sex with transmissible viraemia. This distinction guides safe assessment and avoids unsupported changes to diagnosis, prophylaxis or treatment.

Future blood exposure

Shared injecting equipment can inoculate infected blood and creates a separate prevention and harm-reduction need. This distinction guides safe assessment and avoids unsupported changes to diagnosis, prophylaxis or treatment.

Changing exposure pattern

Partners, source viral suppression, condom use and injecting practice change over time and require repeated assessment.

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

1
Intracellular activation
Tenofovir and emtricitabine are phosphorylated within cells to active metabolites before viral exposure occurs. This distinction guides safe assessment and avoids unsupported changes to diagnosis, prophylaxis or treatment.
2
Chain termination
Active metabolites compete with natural nucleotides and terminate reverse transcription before proviral DNA can form. This distinction guides safe assessment and avoids unsupported changes to diagnosis, prophylaxis or treatment.
3
Tissue persistence
Drug concentrations decline at different rates in rectal, vaginal, neovaginal and blood compartments after dosing stops.

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

Ongoing sexual exposure

Anticipated condomless anal, vaginal or neovaginal sex with potential transmissible HIV supports a PrEP offer.

Injecting exposure

Sharing needles or other injecting equipment creates a blood-risk indication and requires the seven-day stopping tail.

Repeated PEP use

More than one emergency course signals a prevention need and an opportunity for direct transition.

Possible acute HIVRed flag

Fever, rash, sore throat, nodes or diarrhoea after recent risk requires urgent RNA testing.

Breakthrough concernRed flag

New reactivity or detectable RNA during PrEP requires immediate specialist treatment assessment.

HBV-associated stopping riskRed flag

Chronic hepatitis B can rebound when tenofovir-emtricitabine is interrupted or stopped.

Red flags requiring action

Fever, rash, pharyngitis, lymphadenopathy or diarrhoea after recent exposure requires HIV RNA assessment before starting or renewing oral PrEP.
A reactive or discordant HIV result must not be managed by continuing two-drug prophylaxis as if infection were excluded.
Chronic hepatitis B makes intermittent dosing and stopping tenofovir-emtricitabine clinically consequential because HBV rebound can cause hepatitis.
Reduced renal function, proteinuria or concurrent nephrotoxic medicine requires regimen and monitoring review before oral tenofovir disoproxil.
Pregnancy, breastfeeding and gender-affirming hormones require inclusive specialist discussion but are not automatic reasons to deny effective prevention.

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
Laboratory fourth-generation HIV testFirst step
Why
Exclude established infection before starting and at least every three months during PrEP.
Interpretation and limitations
A negative result may be too early after recent exposure; add RNA when timing, symptoms or antiretroviral use creates doubt.
02
HIV RNA
Why
Detect acute or breakthrough infection when serology is negative or discordant.
Interpretation and limitations
Any detectable or uncertain result during PrEP requires urgent HIV specialist interpretation before routine renewal.
03
Creatinine and eGFR
Why
Establish and monitor renal safety for oral tenofovir disoproxil.
Interpretation and limitations
Frequency and eligibility depend on age, baseline function, comorbidity and nephrotoxic medicines; falling function needs regimen review.
04
HBsAg, anti-HBc and anti-HBs
Why
Identify chronic infection, past exposure, vaccine immunity or susceptibility.
Interpretation and limitations
Chronic HBV complicates event-based dosing and stopping; susceptible people should be offered vaccination.
05
Anatomical-site STI testing
Why
Detect chlamydia and gonorrhoea at every exposed site alongside syphilis and hepatitis assessment.
Interpretation and limitations
A positive result receives organism-specific treatment and partner care without making PrEP continuation conditional on negativity.
06
Pregnancy and medication review
Why
Match prevention to reproductive plans, breastfeeding and interacting or nephrotoxic treatment.
Interpretation and limitations
Pregnancy does not automatically preclude PrEP; seek matched guidance for individual risk and regimen.

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

Established HIV infection

A reactive assay or confirmed viraemia requires complete treatment rather than continued two-drug prevention. This distinction guides safe assessment and avoids unsupported changes to diagnosis, prophylaxis or treatment.

Acute HIV infection

Early fever and rash with negative serology requires RNA testing before PrEP can be used safely.

Past exposure needing PEP

A substantial event within 72 hours belongs to the three-drug emergency prophylaxis pathway. This distinction guides safe assessment and avoids unsupported changes to diagnosis, prophylaxis or treatment.

No HIV transmission route

Saliva, intact-skin contact and social contact do not create a PrEP requirement, though patient preference still deserves discussion.

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

01Worked caseQuick-start before anticipated exposureFirst stepAn HIV-negative adult expects receptive vaginal sex tomorrow and requests oral PrEP today.

1Exclude acute symptoms, send a laboratory HIV test, check renal and hepatitis B status, pregnancy and current medicines.
2Take two tenofovir-emtricitabine tablets 2 to 24 hours before risk when clinically eligible.
3Continue one tablet daily through exposure and for seven days after the last receptive vaginal exposure.
4Arrange results ownership, three-month HIV testing and site-specific STI, renal and adherence follow-up.

02Daily dosingProtect unpredictable or frequent exposureExposure is frequent, may occur without notice or the user prefers a simple routine.

1Start with the guideline quick-start approach once HIV-negative status is adequately established.
2Continue one tablet every day and support a cue, supply continuity and a missed-dose plan.
3When stopping, continue for the anatomy-specific tail after the last exposure and plan HBV monitoring if relevant.

03Event-basedMatch the tail to anatomyExposure can be anticipated and the person can follow an episodic schedule.

1Use a double dose 2 to 24 hours before sex or injecting exposure and continue daily while risk continues.
2Use two post-risk daily doses after anal or insertive sex and seven after receptive vaginal, neovaginal or injecting exposure.
3Choose daily dosing instead if anticipation, adherence or chronic HBV makes episodic use unsafe.

04Reactive resultEscalate possible breakthrough infectionEscalationSerology becomes reactive, RNA is detected or acute symptoms develop during PrEP.

1ConfirmatoryObtain confirmatory antigen-antibody and HIV RNA testing urgently and contact an HIV specialist.
2Do not continue two-drug prophylaxis as though it were complete HIV treatment.
3Create a specialist plan for full ART, resistance testing and HBV-active continuity.

Key medicines and prescribing safety2 treatments · regimens, roles and cautions

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 infection

Missed doses, delayed start, premature stopping or resistant virus can permit acquisition during intended prevention. This distinction guides safe assessment and avoids unsupported changes to diagnosis, prophylaxis or treatment.

Drug resistance

Two-drug exposure during undiagnosed HIV may select emtricitabine or tenofovir resistance mutations. This distinction guides safe assessment and avoids unsupported changes to diagnosis, prophylaxis or treatment.

Renal toxicity

Tenofovir disoproxil can impair proximal tubular function, especially with kidney disease or nephrotoxic medicines. This distinction guides safe assessment and avoids unsupported changes to diagnosis, prophylaxis or treatment.

Hepatitis B flare

Stopping HBV-active prophylaxis can permit viral rebound and clinically important liver inflammation. This distinction guides safe assessment and avoids unsupported changes to diagnosis, prophylaxis or treatment.

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

Repeat laboratory HIV testing at least every three months and test sooner for acute symptoms.
Monitor creatinine and eGFR at the interval determined by age, baseline function and renal risk.
Review HBV status before event-based dosing or stopping and vaccinate susceptible people.
Test chlamydia and gonorrhoea at exposed sites and add syphilis and hepatitis testing according to risk.
Assess adherence, anticipated exposure, side effects, supply and whether daily or event-based dosing still fits.
Review pregnancy intention, contraception and breastfeeding without assuming that pregnancy removes HIV risk.
Investigate reactive or discordant results urgently and arrange complete HIV treatment if infection is confirmed.

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

Eligibility is individual

A person can benefit from PrEP without matching a narrow identity or historic trial category.

Anatomy controls stopping

Drug persistence differs across tissues, so two-day and seven-day post-risk tails cannot be exchanged.

Quick start uses two tablets

A double dose before anticipated exposure accelerates protective drug concentrations under the 2025 guidance.

Two drugs are not treatment

Undiagnosed HIV exposed to tenofovir-emtricitabine alone may select resistance and compromise future options.

HBV turns stopping into care

Withdrawal of HBV-active drugs can trigger hepatic flare and therefore needs a deliberate plan.

STIs do not revoke PrEP

Diagnose and treat each infection while continuing prevention support for the exposure that remains.

11Common pitfallsFrequent interpretation and management errors.

01
Do not start PrEP after a past exposure as a substitute for timely three-drug PEP.
02
Do not rely on an early negative rapid test when acute HIV is plausible.
03
Do not use the two-day tail after receptive vaginal, neovaginal or injecting exposure.
04
Do not stop tenofovir-emtricitabine casually in chronic hepatitis B.
05
Do not renew indefinitely without HIV and renal monitoring.
06
Do not restrict access through identity assumptions or make it conditional on an STI-free screen.

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