Risk of Drug Resistance Among Persons Acquiring HIV Within a Randomized Clinical Trial of Single- or Dual-Agent Preexposure Prophylaxis
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Date
2015Author
Baeten, Jared M.
Connor, O. McCoy
Julie, F. Weis
Dylan, Peterson
Mbara, Gerald
Deborah, Donnell
Weis, Julie F.
Dylan, Peterson
Gerald, Mbara
Deborah, Donnell
Katherine, K. Thomas
Craig, W. Hendrix
Mark, A. Marzinke
Lisa, Frenkel
Ndase, Patrick
Mugo, Nelly R.
Celum, Connie
Julie, Overbaugh
Frederick, A. Matsen
Language
enMetadata
Show full item recordAbstract
Background. Preexposure prophylaxis (PrEP) with emtricitabine plus tenofovir disoproxil fumarate (FTC/TDF) or TDF alone reduces the risk of human immunodeficiency virus (HIV) acquisition. Understanding the risk of antiretroviral resistance selected by PrEP during breakthrough infections is important because of the risk of treatment failure during subsequent antiretroviral use.
Methods. Within the largest randomized trial of FTC/TDF versus TDF as PrEP, plasma samples were tested for HIV with resistance mutations associated with FTC (K65R and M184IV) and TDF (K65R and K70E), using 454 sequencing.
Results. Of 121 HIV seroconverters, 25 received FTC/TDF, 38 received TDF, and 58 received placebo. Plasma drug levels in 26 individuals indicated PrEP use during or after HIV acquisition, of which 5 had virus with resistance mutations associated with their PrEP regimen. Among those with PrEP drug detected during infection, resistance was more frequent in the FTC/TDF arm (4 of 7 [57%]), compared with the TDF arm (1 of 19 [5.3%]; P = .01), owing to the FTC-associated mutation M184IV. Of these cases, 3 had unrecognized acute infection at PrEP randomization, and 2 were HIV negative at enrollment.
Conclusions. These results suggest that resistance selected by PrEP is rare but can occur both with PrEP initiation during acute seronegative HIV infection and in PrEP breakthrough infections and that FTC is associated with a greater frequency of resistance mutations than TDF.
Publisher
University of Nairobi
Collections
- Faculty of Health Sciences (FHS) [10377]