Systematic review of clinical trials and cohort studies evaluating HIV post-exposure prophylaxis (PEP) regimens to inform updated Canadian guidelines

BACKGROUND: We conducted a systematic review of clinical trials and cohort studies on HIV post-exposure prophylaxis (PEP) regimens to inform updated 2025 Canadian guidelines. METHODS: We searched Medline and Embase (July 2017-June 2024) for studies reporting on: HIV acquisition, PEP completion, adverse events (AEs) leading to discontinuation and/or moderate to severe adverse events. Two reviewers independently screened abstracts and publications and extracted data from eligible articles. RESULTS: Of 5226 abstracts screened, we retrieved 112 full-text articles and included 22. Median study size was 160 (range = 52-26 988) participants. Regimens included DTG + TDF/XTC (n = 4, 18%), EVG/c/TDF/FTC (n = 4, 18%), BIC/TAF/FTC (n = 4, 18%), RAL + TDF/FTC (n = 4, 18%), EVG/c/TAF/FTC (n = 3, 14%), RPV/TDF/FTC (n = 2, 9%), DOR/TDF/FTC (n = 2, 9%), MVC + TDF/FTC (n = 1, 5%), a wide variety of protease inhibitor-based regimens (n = 7, 32%) and novel combinations with the injectable fusion inhibitor albuvirtide (n = 1, 5%); a third of studies included three or more regimens (n = 8, 36%). Among studies examining PEP completion rates (n = 12, 55%), cumulative completion rate was 86.6% (7779/8983 PEP episodes) and appeared highest for RAL + TDF/FTC, BIC/FTC/TAF and DOR/TDF/3TC at 96.4%, 96.3% and 95.0%, respectively. PEP tolerability was good, with few discontinuations due to adverse events; where data were available, this was lowest for INSTI-based regimens at 0.5% (pooled across two studies) for RAL + TDF/FTC, 1.0% (1/99) for DTG + TDF/XTC, 1.8% (2/109) for BIC/TAF/FTC and zero with albuvirtide (0/198). HIV seroconversions were rare (n = 5/8134, 0.06%) and often related to premature PEP discontinuation or repeated exposures. CONCLUSIONS: Multiple PEP regimens have been associated with high completion, good tolerability and rare seroconversion, supporting their inclusion in clinical guidelines.