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J Infect Dis. 2015 Apr 15;211(8):1211-8. doi: 10.1093/infdis/jiu677. Epub 2015 Jan 13.

Risk of drug resistance among persons acquiring HIV within a randomized clinical trial of single- or dual-agent preexposure prophylaxis.

Author information

1
Division of Human Biology Department of Global Health.
2
Department of Global Health Department of Medicine Department of Epidemiology, University of Washington.
3
Division of Public Health Sciences.
4
Division of Human Biology.
5
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center Department of Global Health.
6
Department of Global Health.
7
Department of Medicine Department of Pharmacology and Molecular Sciences, Johns Hopkins School of Medicine Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
8
Seattle Children's Research Institute, Seattle, Washington.
9
Department of Global Health Kenyatta National Hospital, University of Nairobi, Kenya.
10
Division of Human Biology Division of Public Health Sciences.

Abstract

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.

KEYWORDS:

HIV; HIV prevention; antiretroviral resistance; pre-exposure prophylaxis

PMID:
25587020
PMCID:
PMC4402339
DOI:
10.1093/infdis/jiu677
[Indexed for MEDLINE]
Free PMC Article

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