Drug-Susceptible HIV-1 Infection Despite Intermittent Fixed-Dose Combination Tenofovir/Emtricitabine as Prophylaxis Is Associated With Low-Level Viremia, Delayed Seroconversion, and an Attenuated Clinical Course

Abstract

Continued high rates of HIV-1 transmission have fueled interest in the use of antiretrovirals to prevent infection. Attenuated infection with failure of tenofovir as prophylaxis has been reported in animal models. Here, we report a case of HIV-1 infection despite intermittent use of fixed-dose combination tenofovir and emtricitabine (FTC). The patient was treated with tenofovir DF/FTC for reported repeated high-risk sexual exposures. After seroconversion, he was subjected to routine laboratory testing, CCR5 and HLA genotyping, and biopsy of gastrointestinal (GI) tissue. Resistance testing was performed both as bulk sequencing of plasma and cloning and sequencing of virus derived from plasma, peripheral blood mononuclear cells, and GI tissue. In this patient with no readily identifiable modifying host factors, acute HIV-1 infection with tenofovir DF/FTC-susceptible HIV-1 was associated with an attenuated clinical course, very low postseroconversion HIV-1 RNA levels, slow kinetics of seroconversion, and relative sparing of mucosal CD4+ T cells in the GI tract. Despite the failure of tenofovir DF/FTC as prophylaxis, selection for drug-resistant transmission did not occur and the blunting of postinfection levels of viremia likely reduced the probability of subsequent forward transmissions during the acute phase. These results support continued investigations of the use of antiretrovirals as a means to reduce HIV-1 transmission.