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Background: Post-exposure prophylaxis (PEP) with ZDV is estimated to reduce occupational HIV transmission by 81%.  There are no effectiveness data in the non-occupational PEP setting.

Methods: Subjects reported a potential sexual or injection drug use exposure to HIV in the prior 72 hours. They were given 2 NRTIs (ZDV + 3TC, D4T + 3TC or D4T + ddI), based upon the source partner’s ARV history, for 28 days. A PI was offered when the source reported detectable HIV RNA on ARV.  HIV antibody testing was performed at baseline and weeks 12, 26 and 52 and behavioral questionnaires at baseline and weeks 26 and 52.

Results: Of 891 enrolled subjects, 700 were evaluable at week 12. Seven seroconversions (1%; 95%CI: 0.4 to 2%) were detected;  6 seroconverters had undetectable HIV RNA in a stored baseline plasma specimen and no ARV resistance mutations in a seroconversion plasma specimen. The other seroconverters had low-level baseline viremia and a mixture at codon 184 at seroconversion indicative of either preexisting infection at the time of PEP initiation or PEP failure.  Median seroconversion HIV RNA was 258,000 copies/mL. Compared to non-seroconverters, seroconverters presented more frequently with receptive anal intercourse exposures (100% vs 50%; p = 0.03) and had a trend toward longer time to ARV initiation (median 45.5 [range 14 to 72.5] hours from exposure vs 32.5 hours; p = 0.11). Only 4 seroconverters knew their partner was HIV⁺. All seroconverters had additional potential HIV exposures in the 6 months preceding PEP; 3 had additional exposures after PEP; 4 seroconverters reported 100% adherence, 1 reported fair adherence, and 2 reported poor adherence. In summary, 3 seroconverters were determined to have probably failed PEP due to incomplete efficacy, late initiation or poor adherence, although pre-PEP exposures also occurred in these seroconverters; 4 seroconverters are possible PEP failures; 3 had exposures after PEP initiation that may be the source of their infections and 1 may have already been infected.

Conclusions: As in the occupational setting, PEP is probably not 100% effective following non-occupational exposures, and primary prevention must be reinforced.  In contrast to the occupational setting, exposures are less likely to be isolated, and biological samples from sources are rarely available to confirm transmission between individuals. Thus, identifying the exposure that results in seroconversion in order to confidently document PEP failure is often not possible. This phenomenon will make future efficacy studies difficult to design.

Keywords: Post-Exposure Prophylaxis; Primary HIV Infection; Seroconversion