HIV testing, PrEP, and PEP

Also known as HIV pre-exposure prophylaxis · HIV post-exposure prophylaxis · HIV screening

GP-fellowship guide to HIV testing, PrEP and PEP: the fourth-generation assay window and when RNA closes the gap, indicator-condition testing (any STI, mono-like illness), informed consent and U=U messaging, PrEP eligibility framed by incidence, daily TDF/FTC (PROUD) versus event-driven dosing (IPERGAY), renal and bone monitoring, PEP within 72 hours for 28 days of triple therapy, acute retroviral syndrome recognition, and linkage to care.

high12 referencesUpdated 22 Aug 202611 min readVerification in progress

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Key points

Fourth-generation antigen/antibody testing detects infection from about 45 days; HIV RNA testing closes the early gap when suspicion is high — antibody-only results are unreliable during seroconversion.^[8]^[9]
Every STI diagnosis and any mononucleosis-like illness warrants an HIV test; acute retroviral syndrome mimics glandular fever with fever, rash, pharyngitis and lymphadenopathy.^[9]
Daily TDF/FTC PrEP reduced HIV incidence by 86% in PROUD; event-driven 2+1+1 dosing achieved 86% relative reduction in IPERGAY for gay men having episodic risk.^[1]^[2]
PEP must begin as soon as possible within 72 hours of exposure and runs 28 days of triple therapy, followed by completion serology.^[7]
Sustained undetectable viral load eliminates sexual transmission: zero linked transmissions across HPTN 052 and PARTNER-2 despite tens of thousands of condomless acts.^[5]^[6]

Overview

HIV prevention has become general-practice work: testing anyone with risk or an indicator condition, prescribing PrEP to people at ongoing risk, delivering PEP after exposures, and messaging U=U to serodiscordant couples. The trials that underpin all four are primary-care relevant and examinable to the decimal.^[1]

The clinical stakes concentrate in two failure modes: the missed early diagnosis (a mononucleosis-like illness sent home without an HIV RNA test) and the prevention gap (a patient at obvious ongoing risk who has never been offered PrEP). Both are general-practice failures, both are correctable in single consultations, and both are examined constantly because they are common.^[9] The consultation tools are simple — normalised testing offers, incidence-framed eligibility, precise dosing counselling, and a 72-hour clock respected without negotiation.

References12Show

[1]McCormack S, Dunn DT, Desai M, Dolling DI, Gafos M, et al. Pre-exposure prophylaxis to prevent the acquisition of HIV-1 infection (PROUD): effectiveness results from the pilot phase of a pragmatic open-label randomised trial. Lancet, 2016.PMID 26364263
[2]Molina JM, Capitant C, Spire B, Pialoux G, Cotte L, et al. On-Demand Preexposure Prophylaxis in Men at High Risk for HIV-1 Infection. N Engl J Med, 2015.PMID 26624850
[3]Antoni G, Tremblay C, Delaugerre C, Charreau I, Cua E, et al. On-demand pre-exposure prophylaxis with tenofovir disoproxil fumarate plus emtricitabine among men who have sex with men with less frequent sexual intercourse: a post-hoc analysis of the ANRS IPERGAY trial. Lancet HIV, 2020.PMID 31784343
[4]Grant RM, Lama JR, Anderson PL, McMahan V, Liu AY, et al. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med, 2010.PMID 21091279
[5]Rodger AJ, Cambiano V, Bruun T, Vernazza P, Collins S, et al. Risk of HIV transmission through condomless sex in serodifferent gay couples with the HIV-positive partner taking suppressive antiretroviral therapy (PARTNER): final results of a multicentre, prospective, observational study. Lancet, 2019.PMID 31056293
[6]Cohen MS, Chen YQ, McCauley M, Gamble T, Hosseinipour MC, et al. Antiretroviral Therapy for the Prevention of HIV-1 Transmission. N Engl J Med, 2016.PMID 27424812
[7]Tanner MR, O'Shea JG, Byrd KM, Johnston M, Dumitru GG, et al. Antiretroviral Postexposure Prophylaxis After Sexual, Injection Drug Use, or Other Nonoccupational Exposure to HIV - CDC Recommendations, United States, 2025. MMWR Recomm Rep, 2025.PMID 40331832
[8]Adhikari EH, Macias D, Gaffney D, White S, Rogers VL, et al. Diagnostic accuracy of fourth-generation ARCHITECT HIV Ag/Ab Combo assay and utility of signal-to-cutoff ratio to predict false-positive HIV tests in pregnancy. Am J Obstet Gynecol, 2018.PMID 29913173
[9]Chu C, Selwyn PA Diagnosis and initial management of acute HIV infection. Am Fam Physician, 2010.PMID 20507048
[10]Klausner JD, Grant RM, Kent CK Detection of acute HIV infections. N Engl J Med, 2005.PMID 16093476
[11]Mulligan K, Glidden DV, Anderson PL, Liu A, McMahan V, et al. Effects of Emtricitabine/Tenofovir on Bone Mineral Density in HIV-Negative Persons in a Randomized, Double-Blind, Placebo-Controlled Trial. Clin Infect Dis, 2015.PMID 25908682
[12]Wohl DA, Spinner CD, Flamm J, Hare CB, Doblecki-Lewis S, et al. HIV-1 infection kinetics, drug resistance, and long-term safety of pre-exposure prophylaxis with emtricitabine plus tenofovir alafenamide (DISCOVER): week 144 open-label extension of a randomised, controlled, phase 3 trial. Lancet HIV, 2024.PMID 39008999