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.
*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.
Correspondence to: Susan H. Eshleman, MD, PhD, Department of Pathology, Johns Hopkins University, School of Medicine, Ross 646, 720 Rutland Avenue, Baltimore, MD 21205 (e-mail: seshlem@jhmi.edu).
Supported by the HIV Prevention Trials Network (HPTN), sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), the National Institute on Drug Abuse (NIDA), the National Institute of Mental Health (NIMH), and the Office of AIDS Research, of the National Institutes of Health (NIH), Dept. of Health and Human Services (DHHS) [grant numbers UM1AI068613 (HPTN Laboratory Center), UM1AI068617 (HPTN Statistical and Data Management Center), and UM1AI068619 (HPTN Core and Operations Center). Additional funding was provided by the Division of Intramural Research, NIAID.
Presented at the 2017 Conference on Retroviruses and Opportunistic Infections; February 13–16, 2017; Seattle, WA.
The following relationship is noted: S.H.E. has performed collaborative research studies with Abbott Diagnostics; Abbott Diagnostics has provided reagents for other research projects. R.K.A. has a grant from Gilead through the University of Michigan. P.L.A. has a grant from Gilead through the University of Colorado at Denver. The remaining authors have no funding or conflicts of interest to disclose.
M.V.S., analyzed data; drafted the manuscript; M.L., HPTN 067 data analyst; E.P.-M., HPTN 067 laboratory center QA/QC representative; Y.Z., performed next generation sequencing for HIV drug resistance testing; S.E.H., assisted with project coordination; performed HIV drug resistance testing; M.A.M., provided oversight for plasma antiretroviral testing; R.K.A., HPTN 067 behavioral scientist; A.R., assisted with drug resistance testing; C.W.H., HPTN 067 protocol pharmacologist; P.L.A., provided oversight for PBMC and DBS antiretroviral testing; K.B., HPTN 067 leadership and operations center representative; L.-G.B., HPTN 067 site PI; F.v.G., HPTN 067 protocol co-chair; S.M., HPTN 067 site PI; J.P.H., HPTN 067 statistician; R.G., HPTN 067 protocol chair; S.H.E., responsible for study design; analyzed data; drafted the manuscript.
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Received December 22, 2016
Accepted March 08, 2017
