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



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.



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.



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.
*Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD; †Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA; ‡Department of Health Behavior and Health Education, School of Public Health, University of Michigan, Ann Arbor, MI; §Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; ‖Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institute of Health, Bethesda, MD; ¶Division of Clinical Pharmacology, Johns Hopkins University School of Medicine, Baltimore, MD; #Department of Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO; **FHI 360, Durham, NC; ††Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; ‡‡Department of Epidemiology and Biostatistics, University of California San Francisco School of Medicine, San Francisco, CA; §§Departments of Medicine and Epidemiology, Columbia University Affiliation at Harlem Hospital, New York, NY; ‖‖Columbia University Mailman School of Public Health, New York, NY; ¶¶Department of Biostatistics, University of Washington, Seattle, WA; and ##University of California, San Francisco Gladstone Institutes, San Francisco, CA.
Mariya V
MV
Sivay
Maoji
M
Li
Estelle
E
Piwowar-Manning
Yinfeng
Y
Zhang
Sarah E
SE
Hudelson
Mark A
MA
Marzinke
Rivet K
RK
Amico
Andrew
A
Redd
Craig W
CW
Hendrix
Peter L
PL
Anderson
Kevin
K
Bokoch
Linda-Gail
LG
Bekker
Frits
F
van Griensven
Sharon
S
Mannheimer
James P
JP
Hughes
Robert
R
Grant
Susan H
SH
Eshleman
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023801:Directly Observed Therapy; D024882:Drug Resistance, Viral / Q000187:drug effects*; D000069480:Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination / Q000627:therapeutic use*; D005260:Female; D006679:HIV Seropositivity / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology; D006801:Humans; D008297:Male; D065129:Pre-Exposure Prophylaxis; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D013019:South Africa / Q000453:epidemiology; D013785:Thailand / Q000453:epidemiology
D019380:Anti-HIV Agents; D000069480:Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination