Prophylactic efficacy of oral emtricitabine and tenofovir disoproxil fumarate combination therapy against a tenofovir-resistant simian/human immunodeficiency virus containing the K65R mutation in macaques

J Infect Dis. 2013 Aug 1;208(3):463-7. doi: 10.1093/infdis/jit189. Epub 2013 Apr 30.

Abstract

Daily preexposure prophylaxis (PrEP) with emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) is a novel strategy for preventing human immunodeficiency virus infection. We investigated in macaques whether FTC/TDF prevents transmission of a tenofovir-resistant simian/human immunodeficiency virus (SHIV) containing the K65R mutation. Six macaques received weekly a dose of FTC/TDF 3 days before rectal SHIV exposures and a second dose 2 hours after. Six untreated animals were controls. Animals were exposed rectally to escalating virus doses weekly for up to 28 weeks. PrEP significantly delayed infection with SHIVK65R (P = .028), although 4 of 6 FTC/TDF-treated macaques were infected at the end of the challenges. These findings highlight the need to closely monitor PrEP efficacy in areas with prevalent K65R.

Keywords: HIV-1 drug resistance; Preexposure prophylaxis; emtricitabine; tenofovir disoproxil fumarate.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenine / administration & dosage
  • Adenine / analogs & derivatives*
  • Administration, Oral
  • Animals
  • Anti-HIV Agents / administration & dosage*
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives*
  • Disease Transmission, Infectious / prevention & control
  • Drug Resistance, Viral*
  • Emtricitabine
  • HIV / drug effects*
  • HIV / genetics
  • Macaca
  • Mutation, Missense
  • Organophosphonates / administration & dosage*
  • Simian Acquired Immunodeficiency Syndrome / prevention & control*
  • Simian Acquired Immunodeficiency Syndrome / virology
  • Simian Immunodeficiency Virus / drug effects*
  • Simian Immunodeficiency Virus / genetics
  • Tenofovir
  • Treatment Outcome

Substances

  • Anti-HIV Agents
  • Organophosphonates
  • Deoxycytidine
  • Tenofovir
  • Emtricitabine
  • Adenine