Background: Post-exposure prophylaxis (PEP) is widely used after exposures to HIV. PEP-associated side effects (SE) often occur, causing discontinuation (D).

Methods: We reviewed data collected in the Italian PEP Registry (08/96–09/02). Cases were analyzed according to gender, initial regimen, and reasons for PEP. Outcomes were development of at least one SE and D (< 28 days). Drop-outs, unavailable data, D because HIV-negative source, and self-withdrawal without SE were excluded. AST/ALT changes were categorized according to the toxicity grading used by the ACTG, modified by Sulkowski et al. Statistical analysis was performed with SPSS or EPIINFO v6.

Results: Enclosed in the analysis were 587 healthcare workers (HCW) and 52 safety/social workers (SSW) occupationally exposed, 87 persons exposed by sexual route, and 95 with other exposures. Regimens were AZT-3TC in 248 (30%) cases and AZT-3TC plus indinavir (426) or nelfinavir (64) in 490 (60%); 24 subjects received nevirapine (NVP). Rates of SE were higher among females (67% vs 61%), among PI-including PEP (67.5% vs 57.3%), and among HCW (70% vs 60% in SSW, 53% sex, 43% other). Similar results were observed in D rate (26.6% vs 22.6%; 26.1% vs 19.7%, and 28% vs 23%, 8%, and 17%, respectively). At multivariate analysis, PI-including PEP (OR 1.50, 95% CI, 1.09–2.06; p 0.01), and occupational exposures in HCW (OR 2.29, 95% CI, 1.65–3.18, p 0.001) were independently associated with an higher risk of SE, and of D (PI: OR 1.54, 95% CI, 1.06–2.24; p 0.02; HCW: OR 2.00, 95% CI, 1.32–3.04; p 0.001). Type and incidence of SE were similar to those reported in the literature. Grade 3 AST/ALT alteration was observed in 2 PI-including PEP (incidence: 0.5 per 100 person-month), while grade 4 was observed in 2 cases of 2-NRTI+NVP PEP (incidence: 17 per 100 person-month among those receiving NVP). In 2-NRTI PEP, 1 grade 3 AST/ALT alteration was observed associated with HCV-seroconversion.

Conclusions: A significantly higher risk of developing SE and D appears independently associated with PI-including PEP and with occupational exposures among HCWs and SSW in comparison to sexual and other exposures. Although on a limited sample, our data confirm a high frequency of severe liver toxicity associated with NVP. Drug-induced hepatotoxicity is rare, often mild-moderate, reversible, and slightly more frequent in the PI-containing PEP.