Characterization of HIV seroconverters in a TDF/FTC PrEP study: HPTN 067/ADAPT

Sivay, Mariya V.; Li, Maoji; Piwowar-Manning, Estelle; Zhang, Yinfeng; Hudelson, Sarah; Marzinke, Mark A.; Amico, K. Rivet; Redd, Andrew; Hendrix, Craig W.; Anderson, Peter; Bokoch, Kevin; Bekker, Linda-Gail; van Griensven, Frits; Mannheimer, Sharon B.; Hughes, James; Grant, Robert M.; Eshleman, Susan H.

Background: HPTN 067/ADAPT evaluated tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) pre-exposure prophylaxis (PrEP) in women (South Africa) and men who have sex with men (Thailand, US). Participants received once-weekly directly observed TDF/FTC (DOT), and were then randomized to daily, time-driven, or event-driven PrEP. This report describes characterization of 12 HIV seroconversion events in this trial.

Methods: HIV rapid testing was performed at study sites. Retrospective testing included: 4th generation assays; HIV RNA testing; Western blot; an HIV-1/2 discriminatory assay; resistance testing; and antiretroviral (ARV) drug testing.

Results: Six of the 12 seroconverters received TDF/FTC in the DOT phase, but were not randomized (3 were acutely infected at enrollment; 2 were infected during the DOT phase; one was not randomized due to pregnancy). One of the six randomized participants had acute infection at randomization but was not diagnosed for 3–4 months because HIV rapid tests were non-reactive; continued daily PrEP use was associated with false-negative antibody tests and low HIV RNA levels. The five participants infected after randomization included four with low adherence to the PrEP regimen, and one who reported a 7-day period without dosing prior to infection. Three participants had TDF/FTC resistance (M184I, K65R), including two who received only four once-weekly TDF/FTC doses; most TDF/FTC mutations were detected by next generation sequencing only.

Conclusions: In HPTN 067/ADAPT, participants who acquired HIV infection had infrequent PrEP dosing or low/suboptimal adherence. Sensitive assays improved detection of HIV infection and drug resistance. Drug resistance was observed with limited PrEP exposure.


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Also Published In

JAIDS Journal of Acquired Immune Deficiency Syndromes

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March 18, 2019


Keywords: Pre-exposure prophylaxis; HIV seroconverter; antiretroviral drugs; resistance; tenofovir; emtricitabine