Summary and Comment

HIV seroconversion occurred in approximately 1% of adults who received PEP after nonoccupational exposure. Whether these seroconversions represent failures of PEP is unclear.

Summary

Antiretroviral therapy is commonly administered for nonoccupational postexposure prophylaxis (PEP), but how effective is it? Researchers in San Francisco evaluated the rate of HIV seroconversion among 702 men and women who initiated PEP following a high-risk exposure to HIV through unprotected sex or intravenous drug use. Subjects received a 28-day course of two NRTIs (AZT/3TC, d4T + 3TC, or d4T + ddI). HIV-antibody testing was done at baseline and at 12 weeks.

HIV seroconversion occurred in seven patients (1%), all men who had reported receptive anal intercourse as their high-risk exposure. Efforts to identify and recruit source partners were unsuccessful, but in four seroconversions, the source partner was known to be HIV-positive. Although the median time to initiation of PEP did not differ significantly between groups (seroconverters, 45.5 hours; nonseroconverters, 32.5 hours), three seroconverters received PEP more than 55.5 hours after exposure. All seroconverters completed 28 days of therapy. At least three seroconverters missed many doses of PEP, but overall, the number of missed doses did not differ significantly between seroconverters and nonseroconverters. Three seroconverters reported high-risk exposures between enrollment and seroconversion, with one subject reporting an HIV-infected partner during that time.

One seroconverter had a low level of HIV RNA at baseline (589 copies/mL and 385 copies/mL on repeat testing). Phylogenetic testing revealed that the viruses from baseline and seroconversion plasma were identical. This individual had received PEP 14 hours after exposure and then underwent baseline laboratory testing 3 days later. Interestingly, the authors did not mention symptoms of acute retroviral syndrome in any of the seroconverters, and viral loads were lower than expected for acute seroconversion. Only two subjects had viral loads >500,000 copies/mL with an unreported end titer.

Comment

Of the seven PEP recipients who seroconverted during this study, three reported no high-risk exposures after PEP initiation and might therefore represent failures of PEP. Each of these patients started PEP more than 45 hours after exposure and received only dual-NRTI treatment. Although the addition of a PI might have improved outcomes, it is also possible that PEP is not highly efficacious in the nonoccupational setting. Until we learn more, primary prevention and risk reduction must be our top priorities. Counseling on risk-behavior modification and the importance of medication adherence should be provided to every patient who presents for possible PEP following a high-risk sexual or needle-sharing exposure. PEP must be prescribed judiciously and administered as early as possible, with an NNRTI or PI added for any high-risk exposures (ACC Mar 1 2005). PEP should not be limited to patients who know the HIV serostatus of their source partner, although further prospective studies are needed to determine the role of PEP in these situations. Finally, when making PEP recommendations, clinicians should consider the patient's specific type of nonoccupational exposure because different kinds of exposures are associated with different levels of transmission risk.

- G. Sonia Nagy, MD

Source

Roland ME et al. Seroconversion following nonoccupational postexposure prophylaxis against HIV. Clin Infect Dis 2005 Nov 15; 41:1507-13.

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