Characterization of HIV Seroconverters in a TDF/FTC PrEP Study: HPTN 067/ADAPT

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

Research output: Contribution to journalArticlepeer-review

Abstract

Background: HIV Prevention Trials Network (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 therapy (DOT) of TDF/FTC, 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 fourth generation assays, HIV RNA testing, Western blot, an HIV-1/2 discriminatory assay, resistance testing, and antiretroviral 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; 1 was not randomized because of pregnancy). One of the 6 randomized participants had acute infection at randomization but was not diagnosed for 3-4 months because HIV rapid tests were nonreactive; continued daily PrEP use was associated with false-negative antibody tests and low HIV RNA levels. The 5 participants infected after randomization included 4 with low adherence to the PrEP regimen, and one who reported a 7-day period without dosing before infection. Three participants had TDF/FTC resistance (M184I, K65R), including 2 who received only 4 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.

Original languageEnglish (US)
Pages (from-to)271-279
Number of pages9
JournalJournal of acquired immune deficiency syndromes
Volume75
Issue number3
DOIs
StatePublished - Jul 1 2017

Keywords

  • HIV seroconverter
  • antiretroviral drugs
  • emtricitabine
  • pre-exposure prophylaxis
  • resistance
  • tenofovir

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

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