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)

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

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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / administration & dosage
  • Anti-HIV Agents / pharmacology
  • Anti-HIV Agents / therapeutic use*
  • Delayed-Action Preparations
  • Drug Resistance, Viral
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / virology*
  • HIV-1 / drug effects*
  • Humans
  • Rilpivirine / administration & dosage
  • Rilpivirine / pharmacology
  • Rilpivirine / therapeutic use*
  • Selection, Genetic

Substances

  • Anti-HIV Agents
  • Delayed-Action Preparations
  • Rilpivirine