Evaluation of a multidrug assay for monitoring adherence to a regimen for HIV preexposure prophylaxis in a clinical study, HIV prevention trials network 073

Yinfeng Zhang, William Clarke, Mark A Marzinke, Estelle Piwowar-Manning, Geetha Beauchamp, Autumn Breaud, Craig Hendrix, Gavin A. Cloherty, Lynda Emel, Scott Rose, Lisa Hightow-Weidman, Marc Siegel, Steven Shoptaw, Sheldon D. Fields, Darrell Wheeler, Susan Eshleman

Research output: Contribution to journalArticle

Abstract

Daily oral tenofovir disoproxil fumarate (TDF)-emtricitabine (FTC) is a safe and effective intervention for HIV preexposure prophylaxis (PrEP). We evaluated the performance of a qualitative assay that detects 20 antiretroviral (ARV) drugs (multidrug assay) in assessing recent PrEP exposure (detection limit, 2 to 20 ng/ml). Samples were obtained from 216 Black men who have sex with men (208 HIV-uninfected men and 8 seroconverters) who were enrolled in a study in the United States evaluating the acceptability of TDF-FTC PrEP (165 of the uninfected men and 5 of the seroconverters accepted PrEP). Samples from 163 of the 165 HIV-uninfected men who accepted PrEP and samples from all 8 seroconverters were also tested for tenofovir (TFV) and FTC using a quantitative assay (detection limit for both drugs, 0.31 ng/ml). HIV drug resistance was assessed in seroconverter samples. The multidrug assay detected TFV and/or FTC in 3 (1.4%) of the 208 uninfected men at enrollment, 84 (40.4%) of the 208 uninfected men at the last study visit, and 1 (12.5%) of the 8 seroconverters. No other ARV drugs were detected. The quantitative assay confirmed all positive results from the multidrug assay and detected TFV and/or FTC in 9 additional samples (TFV range, 0.65 to 16.5 ng/ml; FTC range, 0.33 to 14.6 ng/ml). Resistance mutations were detected in 4 of the 8 seroconverter samples. The multidrug assay had 100% sensitivity and specificity for detecting TFV and FTC at drug concentrations consistent with daily PrEP use. The quantitative assay detected TFV and FTC at lower levels, which also might have provided protection against HIV infection.

Original languageEnglish (US)
Article numbere02743-16
JournalAntimicrobial Agents and Chemotherapy
Volume61
Issue number7
DOIs
Publication statusPublished - Jul 1 2017

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Keywords

  • Adherence
  • Antiretroviral drug
  • HIV
  • HPTN 073
  • Preexposure prophylaxis
  • Truvada

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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