HIV post-exposure prophylaxis

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

PEP is a clinical race against early viral establishment. The consultation therefore has two simultaneous tracks: decide whether the described event could deliver infectious virus, and remove avoidable delay when prophylaxis is justified. Baseline testing protects later interpretation and prescribing, but it does not measure acquisition from an event that has just happened.

A useful risk history separates source characteristics from exposure mechanics. The clinician asks what fluid was present, which tissue encountered it, whether a needle penetrated, and when this occurred. For sexual exposure, a source with confirmed sustained suppression does not transmit HIV. If viraemia is detectable or unknown, the relevant guideline table is applied to the exact route rather than to identity or anxiety alone.

The standard course deliberately combines a two-drug reverse-transcriptase backbone with an integrase inhibitor for 28 days. That is different from oral PrEP and should remain complete unless an HIV specialist changes it. Kidney function, HBV infection, pregnancy, medicines, supplements and possible resistant source virus shape safe prescribing without creating an excuse for administrative delay.

The end of the emergency visit begins the adherence phase. A patient needs tablets, a realistic method for obtaining the whole course, advice about cations and vomiting, and rapid access when adverse effects threaten continuation. Follow-up also completes HBV, HCV, STI and pregnancy pathways on their own schedules.

Repeated presentations identify an unmet prevention need. A non-judgmental conversation can connect the person to PrEP, condoms, vaccination, sterile injecting equipment or help with coercion. Giving PEP now and reducing future risk are parts of the same sexual-health plan.

Key points

Treat PEP assessment as urgent: an indicated course should start as soon as possible, preferably within 24 hours and no later than 72 hours from exposure.
Base the decision on fluid, anatomical route, mucosal or percutaneous injury, source HIV information and documented viral suppression; demographic labels cannot substitute for this history.
Draw baseline laboratory HIV, kidney, liver, hepatitis B and C, pregnancy and exposure-site STI samples promptly, while ensuring that testing does not delay the first dose.
For most UK adults, the standard 28-day course is tenofovir disoproxil/emtricitabine with raltegravir; renal function, pregnancy, HBV, source resistance and interactions may require expert adjustment.
Reliable sustained viral suppression means HIV is not sexually transmitted; use the precise source and exposure context when judging occupational or uncertain adherence scenarios.
Before discharge, secure all 28 days or a dependable supply plan, explain missed or vomited doses, and check minerals or antacids that can interfere with raltegravir.
Schedule the concluding fourth-generation HIV test at least 45 days after the last PEP dose, which is at least 73 days after exposure when the full 28-day course was taken.
If further exposures are likely, arrange direct transition from PEP into a PrEP assessment; PrEP cannot retrospectively replace the required three-drug course.

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

Mucosal inoculation during sex

HIV exposure becomes plausible when infectious genital, rectal or blood-containing fluid reaches susceptible rectal, vaginal, penile or oral mucosa; tissue trauma and source viraemia modify probability.

Direct blood inoculation

A hollow-bore sharp or shared injecting equipment can carry residual infected blood through the skin, bypassing the protection of an intact surface.

Contact without an entry route

Intact skin blocks acquisition, and fluids such as saliva alone do not contain enough infectious virus to create a PEP indication.

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

1
An early preventable interval
After virus crosses a barrier, infection begins in a limited population of susceptible cells before amplification and durable reservoirs make eradication impossible; this explains the 72-hour ceiling and preference for treatment within 24 hours.
2
Blocking viral DNA production
Tenofovir and emtricitabine are phosphorylated inside cells and compete during reverse transcription, interrupting the DNA copy needed for continued replication.
3
Preventing chromosomal insertion
Raltegravir inhibits integrase, adding protection at a later replication step before viral DNA becomes part of the host-cell genome.

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

Eligible sexual routeRed flag

Condomless receptive anal or vaginal contact can warrant PEP when source virus may be transmissible; timing and reliable suppression determine the decision.

Blood inoculationRed flag

A blood-filled hollow-bore needle injury or shared injecting equipment offers direct access through the skin and needs immediate assessment.

Non-intact mucosal contactRed flag

Blood reaching an eye, mouth or damaged skin differs clinically from blood resting on intact skin, which does not transmit HIV.

No meaningful HIV route

Everyday touch, saliva alone and contact confined to intact skin do not supply the infectious-fluid and tissue combination required for PEP.

Possible infection predating PEPRed flag

A compatible systemic illness already underway may signal earlier acquisition, so RNA testing and specialist review accompany any prevention decision.

Ongoing exposure pattern

Another likely sexual or injecting exposure after this course makes planned PrEP and broader prevention support clinically preferable to disconnected emergency visits.

Red flags requiring action

A person close to the 72-hour boundary needs a prescribing decision now, with referral arranged after the first dose if PEP is indicated.
Fever, rash, sore throat or lymph-node enlargement that started before this presentation may represent HIV acquired earlier and calls for urgent antigen–antibody and RNA testing.
A reactive or unresolved baseline HIV result changes the task from prevention to diagnostic assessment; a two-drug PrEP regimen must not be used to cover uncertainty.
Renal disease or chronic hepatitis B affects tenofovir and emtricitabine management, but a clearly eligible exposure still needs immediate specialist-supported action.
Pregnancy and breastfeeding require an informed urgent regimen review and are not reasons to refuse otherwise indicated prophylaxis.
After sexual assault, address injuries, emergency contraception, hepatitis B prevention, other STI care, safeguarding and forensic choices in the same trauma-informed pathway.

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 assayFirst step
Why
Identify established infection and create the serological starting point for post-course testing.
Interpretation and limitations
A negative baseline result cannot clear the exposure that has just occurred; recent symptoms, PrEP or PEP may also require HIV RNA and specialist interpretation.
02
HIV RNA when acute infection is plausible
Why
Look for viraemia before the usual antigen and antibody pattern is conclusive.
Interpretation and limitations
An acute syndrome or antiretroviral-altered result is not safely resolved by starting two-drug PrEP; involve the HIV team urgently.
03
Consented source testing and treatment record
Why
Determine whether source infection and sustained suppression are reliably documented.
Interpretation and limitations
This evidence can stop or avoid unnecessary PEP, but obtaining it must not defer treatment for an otherwise eligible event.
04
Creatinine with estimated GFR
Why
Provide a baseline for tenofovir disoproxil safety and identify substantial kidney impairment.
Interpretation and limitations
Collect promptly and modify with specialist help when necessary; a pending result need not hold the first dose after a clear high-risk exposure.
05
Hepatitis B marker panel
Why
Distinguish immunity, susceptibility and chronic infection before a tenofovir/emtricitabine course ends.
Interpretation and limitations
HBsAg, anti-HBc and anti-HBs guide vaccination and continuity planning because withdrawal of HBV-active drugs can precipitate hepatitis.
06
Hepatitis C, pregnancy and anatomical-site STI tests
Why
Assess other consequences carried by the same event and choose site-appropriate follow-up.
Interpretation and limitations
A baseline result has its own window limits; pregnancy informs prescribing, and exposed throat, genital or rectal sites are sampled according to the history.
07
Complete product and interaction inventory
Why
Find renal hazards and factors that reduce raltegravir exposure or make completion difficult.
Interpretation and limitations
Include non-prescription antacids, calcium, iron, magnesium, herbal and recreational products, then give product-specific timing advice.

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

Anxiety after a non-transmissible event

A careful fluid-and-route account may show no biological HIV exposure; the patient still benefits from explanation and any relevant sexual-health screen.

HIV already established

Systemic symptoms predating the index event or a reactive baseline test point away from prophylaxis alone and toward urgent confirmatory and RNA assessment.

Hepatitis exposure

The same blood or sexual event may transmit HBV or HCV, whose vaccination, immunoglobulin, testing and follow-up decisions are separate from HIV PEP.

Another sexually transmitted infection

Gonorrhoea, chlamydia and syphilis can accompany the exposure without changing PEP eligibility, so each anatomical site and organism needs its own pathway.

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

0118-hour caseStart without administrative delayFirst stepAn adult attends 18 hours after receptive anal sex with a source known to have untreated HIV.

1Confirm timing, route, fluid, source treatment information, consent circumstances and medicines while checking for injury or other urgent needs.
2Collect HIV, renal, liver, hepatitis, pregnancy and site-directed STI samples as applicable without waiting for their results.
3Give tenofovir disoproxil/emtricitabine plus raltegravir immediately and arrange uninterrupted access to the complete 28-day supply.
4Book early review for results, tolerance, adherence, interactions and a plan for risk after the course.

02Course reviewComplete and test after PEPThe first PEP dose has been issued from an emergency or sexual-health service.

1Check within the early treatment period that tablets were obtained and clarify food, cation, missed-dose and vomiting instructions.
2Resolve toxicity or interaction problems quickly so the person can complete 28 days unless expert reassessment removes the indication.
3Arrange the final laboratory fourth-generation HIV assay at least 45 days after completion, and investigate compatible acute illness sooner with RNA.

03Complex prescribingProtect efficacy in a special contextKidney impairment, chronic HBV, pregnancy, breastfeeding or suspected source resistance complicates the usual regimen.

1Do not lose the prevention window: start the safest immediately available indicated regimen with urgent HIV specialist support.
2Use the individual renal result, HBV treatment need, pregnancy evidence, formulation and source resistance history to refine the prescription.
3Record who will review results, supply the remaining doses and supervise any later change or cessation.

04Next-exposure planBridge from PEP to preventionThe history indicates that similar sexual or injecting exposure may recur.

1At the end of PEP, reassess HIV status and resolve symptoms or discordant results before selecting PrEP.
2Start PrEP at the guideline transition point with renal, hepatitis B and adherence planning specific to the intended dosing pattern.
3Offer site-based STI testing, vaccination, condoms, sterile equipment and safeguarding support according to the person’s goals.

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

The paired nucleotide and nucleoside analogues limit formation of viral DNA while the exposure remains preventable.

Tenofovir disoproxil 245 mg with emtricitabine 200 mg

Take one combined tablet by mouth once daily as the backbone of a 28-day PEP course.

Review kidney function, concurrent nephrotoxins and hepatitis B; stopping HBV-active therapy in chronic infection requires a planned alternative or liver monitoring.

Integrase inhibition adds a third active drug so newly made viral DNA cannot establish productive infection.

Raltegravir

Take 1200 mg by mouth once daily for 28 days together with tenofovir disoproxil and emtricitabine in the standard UK adult course.

Confirm the formulation, check pregnancy and all interactions, and give explicit advice about polyvalent-cation antacids and supplements.

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

HIV acquisition despite prophylaxis

A late start, incomplete dosing, continuing exposure or resistant source virus can allow infection; a reactive follow-up result needs prompt complete ART and resistance-informed care.

Interrupted course

Short starter supplies, adverse effects or access barriers can create missed doses, reducing effective drug coverage during the period it matters most.

Tenofovir-related renal harm

Tenofovir disoproxil can affect proximal tubular function, so pre-existing renal impairment and other nephrotoxic medicines alter monitoring and regimen choice.

Hepatitis B rebound after stopping

In chronic HBV, ending tenofovir/emtricitabine removes antiviral pressure and can provoke a clinically important hepatic flare unless cessation is planned.

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

Document the actual exposure time and the first administered dose so any delay is clear.
Confirm early that the patient has a route to all 28 days and can describe what to do after a missed or vomited dose.
Review kidney, liver, hepatitis B and pregnancy results promptly, changing treatment with specialist input when indicated.
Reconcile prescription medicines, antacids, mineral supplements, herbal products and recreational substances for interactions.
Perform the final laboratory HIV test at least 45 days after PEP completion and use RNA sooner if an acute syndrome develops.
Complete hepatitis C, syphilis and anatomical-site STI testing at the appropriate separate intervals.
Arrange PrEP without a prevention gap when the post-course assessment shows continuing risk.

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

History drives eligibility

Transmission requires a relevant fluid and route, so describe the event anatomically before reaching for a risk label.

Baseline cannot close today

Immediate HIV testing can find infection acquired earlier but cannot exclude infection from the event that prompted this attendance.

Treatment and tests run together

Collecting useful samples matters, yet prophylactic benefit is time dependent and must not wait for routine laboratory turnaround.

Three drugs are deliberate

A two-drug PrEP supply is not equivalent to the complete standard PEP regimen after a qualifying exposure.

The follow-up clock restarts

Final testing is counted from the end of prophylaxis because antiretrovirals can alter the appearance of diagnostic markers.

Prevention continues after day 28

A direct PrEP transition is safer and easier to follow than repeated isolated emergency courses when exposure is ongoing.

11Common pitfallsFrequent interpretation and management errors.

01
Do not turn source testing, renal results or referral logistics into a delay before indicated PEP.
02
Do not routinely begin PEP after 72 hours as though evidence supported later initiation.
03
Do not infer risk from a person’s identity when fluid, route and source viraemia are the relevant variables.
04
Do not replace the standard three-drug course with two-drug PrEP.
05
Do not overlook HBV continuity, renal safety, pregnancy or cation interactions during an urgent prescription.
06
Do not date the final HIV assay from exposure when the recommendation is at least 45 days after course completion.

Find your next topic