No evidence for selection of HIV-1 with enhanced gag-protease or Nef function among breakthrough infections in the CAPRISA 004 tenofovir microbicide trial

Denis R Chopera; Jaclyn K Mann; Philip Mwimanzi; Saleha Omarjee; Xiaomei T Kuang; Nonkululeko Ndabambi; Sarah Goodier; Eric Martin; Vivek Naranbhai; Salim Abdool Karim; Quarraisha Abdool Karim; Zabrina L Brumme; Thumbi Ndung'u; Carolyn Williamson; Mark A Brockman; CAPRISA 004 TRAPS Team

doi:10.1371/journal.pone.0071758

No evidence for selection of HIV-1 with enhanced gag-protease or Nef function among breakthrough infections in the CAPRISA 004 tenofovir microbicide trial

PLoS One. 2013 Aug 28;8(8):e71758. doi: 10.1371/journal.pone.0071758. eCollection 2013.

Authors

Denis R Chopera¹, Jaclyn K Mann, Philip Mwimanzi, Saleha Omarjee, Xiaomei T Kuang, Nonkululeko Ndabambi, Sarah Goodier, Eric Martin, Vivek Naranbhai, Salim Abdool Karim, Quarraisha Abdool Karim, Zabrina L Brumme, Thumbi Ndung'u, Carolyn Williamson, Mark A Brockman; CAPRISA 004 TRAPS Team

Affiliation

¹ HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa ; KwaZulu-Natal Research Institute for Tuberculosis and HIV, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa ; Institute of Infectious Disease and Molecular Medicine, and the Division of Medical Virology, University of Cape Town and National Health Laboratory Services, Cape Town, South Africa ; Faculty of Health Sciences, Simon Fraser University, Burnaby, British Columbia, Canada ; British Columbia Centre for Excellence in HIV/AIDS, Vancouver, British Columbia, Canada.

Abstract

Background: Use of antiretroviral-based microbicides for HIV-1 prophylaxis could introduce a transmission barrier that inadvertently facilitates the selection of fitter viral variants among incident infections. To investigate this, we assessed the in vitro function of gag-protease and nef sequences from participants who acquired HIV-1 during the CAPRISA 004 1% tenofovir microbicide gel trial.

Methods and results: We isolated the earliest available gag-protease and nef gene sequences from 83 individuals and examined their in vitro function using recombinant viral replication capacity assays and surface protein downregulation assays, respectively. No major phylogenetic clustering and no significant differences in gag-protease or nef function were observed in participants who received tenofovir gel versus placebo gel prophylaxis.

Conclusion: Results indicate that the partial protective effects of 1% tenofovir gel use in the CAPRISA 004 trial were not offset by selection of transmitted/early HIV-1 variants with enhanced Gag-Protease or Nef fitness.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adenine / administration & dosage
Adenine / analogs & derivatives*
Adenine / pharmacology
Anti-HIV Agents / administration & dosage
Anti-HIV Agents / pharmacology*
Clinical Trials as Topic
Female
HIV Infections / prevention & control
HIV Infections / transmission
HIV Infections / virology*
HIV-1 / drug effects
HIV-1 / enzymology
HIV-1 / genetics*
Humans
Organophosphonates / administration & dosage
Organophosphonates / pharmacology*
Phylogeny
Sequence Analysis, DNA
Tenofovir
Vaginal Creams, Foams, and Jellies / administration & dosage
Vaginal Creams, Foams, and Jellies / pharmacology*
Virus Replication
gag Gene Products, Human Immunodeficiency Virus / genetics
nef Gene Products, Human Immunodeficiency Virus / genetics

Substances

Anti-HIV Agents
Organophosphonates
Vaginal Creams, Foams, and Jellies
gag Gene Products, Human Immunodeficiency Virus
nef Gene Products, Human Immunodeficiency Virus
nef protein, Human immunodeficiency virus 1
Tenofovir
Adenine

Abstract

Publication types

MeSH terms

Substances

Grants and funding