Key Facts

HIV prophylaxis encompasses pharmacological and non-pharmacological strategies to prevent HIV acquisition. PrEP has transformed HIV prevention and is a cornerstone of the UK's goal to end new HIV transmissions by 2030.

Epidemiology

• New HIV diagnoses in UK declining: ~3,118 in 2022 (vs 6,000+ in 2014)
• Decline attributed to combination prevention: increased testing, PrEP, U=U
• PrEP uptake in UK: >40,000 people accessing PrEP via NHS
• Mother-to-child transmission: <0.5% in UK with interventions
• Occupational exposure: extremely rare in UK (<1 seroconversion per year with PEP)

Aetiology

Risk factors for HIV acquisition:

• Condomless anal intercourse (highest per-act risk: 1.4% receptive)
• Multiple sexual partners
• STI co-infection (increases risk 2–5 fold)
• IV drug use with shared needles
• Occupational needlestick injury
• Vertical transmission (without interventions: 15–45%)

Pathophysiology

PrEP mechanism:

• Tenofovir/emtricitabine (NRTIs): achieve high drug concentrations in genital/rectal tissues
• Block reverse transcriptase → prevent proviral DNA integration
• Rectal tissue: protective levels in ~7 days; vaginal tissue: ~20 days of daily dosing

PEP mechanism:

• ART started after exposure blocks viral replication before systemic dissemination
• Must start within 72 hours (ideally within 24 hours) — efficacy decreases with delay
• 28-day course eliminates virus before chronic infection establishes

PrEP Assessment

• Patient presents requesting PrEP — ongoing high-risk exposure
• MSM with condomless sex with casual partners
• HIV-negative partner of person living with HIV (if partner not virally suppressed)
• Heterosexual with partners from high-prevalence areas
• IVDU with sharing practices

PEP Assessment

• Sexual exposure: unprotected sex with known/suspected HIV+ partner
• Occupational exposure: needlestick, sharps injury, mucosal splash
• Assess within hours: timeliness is critical

PMTCT Assessment

• Antenatal HIV screening (offered to all pregnant women in UK)
• Planning delivery method and neonatal prophylaxis

Red Flags

• Symptoms suggestive of acute HIV seroconversion (must test and exclude before starting PrEP)
• Renal impairment (eGFR <60 — relative contraindication for TDF-based PrEP)
• Hepatitis B co-infection (TDF/FTC treats HBV — stopping PrEP can cause HBV flare)
• PEP request >72 hours post-exposure (unlikely to be effective)

Before Starting PrEP

• HIV test (4th-gen): must be NEGATIVE — essential to exclude existing infection
• Hepatitis B serology: HBsAg, anti-HBs, anti-HBc (TDF/FTC active against HBV)
• Hepatitis C antibody: if risk factors
• Renal function: eGFR must be >60 (TDF nephrotoxicity risk)
• STI screen: full screen including syphilis, chlamydia, gonorrhoea
• Pregnancy test: if applicable

Monitoring on PrEP (every 3 months)

• HIV test (4th-gen)
• Renal function (eGFR)
• STI screen
• Hepatitis C if ongoing risk
• Adherence assessment

Before Starting PEP

• Baseline HIV test: document HIV-negative status
• Source patient testing: if available and consenting
• Hepatitis B/C serology: co-infection
• FBC, U&Es, LFTs: baseline
• Pregnancy test: if applicable
• STI screen

PEP Follow-up

• HIV test at 8–12 weeks post-exposure (to confirm no seroconversion)
• Repeat hepatitis B/C at 3 and 6 months

Non-pharmacological

• Condom use: remains the cornerstone of combination prevention
• Regular STI testing: at least annually, every 3 months for high-risk groups
• Partner notification and treatment
• Needle exchange programmes: for IVDU
• Combination prevention: PrEP + condoms + regular testing + treatment as prevention (U=U)

Pharmacological

Pre-exposure prophylaxis (PrEP):

• Daily PrEP: tenofovir disoproxil 245mg/emtricitabine 200mg (Truvada) — 1 tablet OD
• On-demand PrEP (MSM only — IPERGAY): 2 tablets 2–24h before sex, 1 tablet 24h later, 1 tablet 48h after first dose
• Efficacy: >99% with consistent use (PROUD trial showed 86% reduction in intention-to-treat)
• Continue until risk has resolved; if stopping, continue for 7 days after last exposure (28 days for vaginal exposure)

Post-exposure prophylaxis (PEP):

• Regimen: tenofovir disoproxil/emtricitabine + raltegravir 400mg BD for 28 days
• Must start within 72 hours (preferably within 24 hours)
• Available from sexual health clinics and A&E departments
• Side effects: nausea, diarrhoea, headache (usually mild and self-limiting)

PMTCT:

• Maternal ART: throughout pregnancy, labour, and postpartum — aim for VL <50 copies/mL by 36 weeks
• Delivery: vaginal delivery if VL <50; consider elective C-section at 38 weeks if VL >400 at 36 weeks
• Neonatal prophylaxis: zidovudine monotherapy (low risk) or triple ART (high risk) for 2–4 weeks
• Avoid breastfeeding in UK (formula feeding recommended) — though BHIVA now supports informed choice if VL undetectable

Landmark trials:

• iPrEx: first PrEP efficacy trial (MSM) — 44% reduction in ITT, >90% with adherence
• PROUD: UK open-label PrEP trial — 86% reduction
• DISCOVER: TAF/FTC non-inferior to TDF/FTC for PrEP
• IPERGAY: on-demand PrEP — 86% reduction in MSM
• HPTN 052: early ART reduced transmission by 96%

Referral Criteria

• PrEP: sexual health clinic assessment
• PEP: A&E or sexual health clinic within 72 hours
• PMTCT: specialist HIV antenatal clinic
• Occupational exposure: occupational health + A&E within hours

• PrEP: virtually eliminates HIV acquisition risk when taken consistently (>99% efficacy)
• PEP: estimated 80% effective if started within 72 hours
• PMTCT: reduces transmission from 15–45% to <0.5%
• U=U: zero sexual transmissions documented with sustained VL <200 (PARTNER studies: 0 transmissions in >77,000 condomless acts)
• UK on track to meet 2030 target of zero new HIV transmissions
• Late PEP (>72 hours): not recommended — effectiveness unproven

PEP Risk Assessment

PrEP Monitoring Schedule