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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

Prada, Nicole PhD*; Davis, Brandi BS*; Jean-Pierre, Patrick MS*; Roche, Matthew La BS*; Duh, Fuh-Mei MS; Carrington, Mary PhD; Poles, Michael MD; Mehandru, Saurabh MD*; Mohri, Hiroshi MD, PhD*; Markowitz, Martin MD*

JAIDS Journal of Acquired Immune Deficiency Syndromes: October 2008 - Volume 49 - Issue 2 - p 117-122
doi: 10.1097/QAI.0b013e3181869a9b
Rapid Communication

Background: 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).

Methods: 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.

Results: 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.

Conclusions: 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.

From the *Aaron Diamond AIDS Research Center, Rockefeller University, New York, NY; †SAIC-Frederick, NCI-Frederick, Frederick, MD; and ‡Department of Medicine, New York University School of Medicine, New York, NY.

Received for publication March 12, 2008; accepted June 24, 2008.

Supported by funding from the National Institutes of Health RO1-AI47033, and the Acute Infection and Early Disease Research Program, AI41534, and the Clinical and Translational Science Award UL1 RR024143.

Correspondence to: Martin Markowitz, MD, Aaron Diamond AIDS Research Center, 455 First Avenue, 7th Floor, New York, NY 10016 (e-mail: mmarkowitz@adarc.org).

© 2008 Lippincott Williams & Wilkins, Inc.