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J Infect Dis. 2016 Mar 15;213(6):1013-7. doi: 10.1093/infdis/jiv528. Epub 2015 Nov 12.

Selection of Rilpivirine-Resistant HIV-1 in a Seroconverter From the SSAT 040 Trial Who Received the 300-mg Dose of Long-Acting Rilpivirine (TMC278LA).

Author information

1
Division of Infectious Diseases, Department of Medicine, University of Pittsburgh School of Medicine, Pennsylvania.
2
Liverpool Bioanalytical Facility, Department of Molecular and Clinical Pharmacology, University of Liverpool.
3
Department of HIV/Genito-Urinary Medicine, St. Stephen's Centre, Chelsea and Westminster Hospital, London, United Kingdom.

Abstract

The injectable long-acting formulation of rilpivirine (TMC278LA) is a promising preexposure prophylaxis (PrEP) candidate for prevention of human immunodeficiency virus type 1 (HIV-1) infection. We evaluated HIV-1 in plasma obtained from an unexpected seroconverter in the 300-mg arm of the SSAT040 TMC278LA pharmacokinetic study for rilpivirine (RPV) resistance. Infection with wild-type HIV-1 was confirmed on day 84 after TMC278LA injection, and the K101E mutation was detected on day 115. Plasma-derived HIV-1 clones containing K101E had 4-fold increased resistance to RPV and 4-8-fold increased cross-resistance to etravirine, nevirapine, and efavirenz compared with wild type HIV-1 plasma-derived clones from the same individual. This case is a unique instance of infection with wild-type HIV-1 and subsequent selection of resistant virus by persistent exposure to long-acting PrEP.

KEYWORDS:

HIV-1; NNRTI resistance; TMC278LA; pre-exposure prophylaxis (PrEP); rilpivirine

PMID:
26563240
DOI:
10.1093/infdis/jiv528
[Indexed for MEDLINE]

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