Antiretroviral Pre-Exposure Prophylaxis Does Not Enhance Immune Responses to HIV in Exposed but Uninfected Persons

Pattacini, Laura; Murnane, Pamela M.; Baeten, Jared M.; Fluharty, Tayler R.; Thomas, Katherine K.; Bukusi, Elizabeth; Katabira, Elly; Mugo, Nelly; Donnell, Deborah; Lingappa, Jairam R.; Celum, Connie; Marzinke, Mark; McElrath, M. Juliana; Lund, Jennifer M.
June 2015
Journal of Infectious Diseases;6/15/2015, Vol. 211 Issue 12, p1943
Academic Journal
Background. Antiretroviral preexposure prophylaxis (PrEP), using daily oral combination tenofovir disoproxil fumarate plus emtricitabine, is an effective human immunodeficiency virus (HIV) prevention strategy for populations at high risk of HIV acquisition. Although the primary mode of action for the protective effect of PrEP is probably direct antiviral activity, nonhuman primate studies suggest that PrEP may also allow for development of HIV-specific immune responses, hypothesized to result from aborted HIV infections providing a source of immunologic priming. We sought to evaluate whether PrEP affects the development of HIV-specific immune response in humans. Methods and Results. Within a PrEP clinical trial among high-risk heterosexual African men and women, we detected HIV-specific CD4+ and CD8+ peripheral blood T-cell responses in 10%-20% of 247 subjects evaluated. The response rate and magnitude of T-cell responses did not vary significantly between those assigned PrEP versus placebo, and no significant difference between those assigned PrEP and placebo was observed in measures of innate immune function. Conclusions. We found no evidence to support the hypothesis that PrEP alters either the frequency or magnitude of HIV-specific immune responses in HIV-1-exposed seronegative individuals. These results suggest that PrEP is unlikely to serve as an immunologic prime to aid protection by a putative HIV vaccine


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