title: No evidence for selection of HIV-1 with enhanced gag-protease or Nef function among breakthrough infections in the CAPRISA 004 tenofovir microbicide trial.
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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Denis R
authors.initials: DR
authors.lastname: Chopera
authors.forename: Jaclyn K
authors.initials: JK
authors.lastname: Mann
authors.forename: Philip
authors.initials: P
authors.lastname: Mwimanzi
authors.forename: Saleha
authors.initials: S
authors.lastname: Omarjee
authors.forename: Xiaomei T
authors.initials: XT
authors.lastname: Kuang
authors.forename: Nonkululeko
authors.initials: N
authors.lastname: Ndabambi
authors.forename: Sarah
authors.initials: S
authors.lastname: Goodier
authors.forename: Eric
authors.initials: E
authors.lastname: Martin
authors.forename: Vivek
authors.initials: V
authors.lastname: Naranbhai
authors.forename: Salim Abdool
authors.initials: SA
authors.lastname: Karim
authors.forename: Quarraisha Abdool
authors.initials: QA
authors.lastname: Karim
authors.forename: Zabrina L
authors.initials: ZL
authors.lastname: Brumme
authors.forename: Thumbi
authors.initials: T
authors.lastname: Ndung'u
authors.forename: Carolyn
authors.initials: C
authors.lastname: Williamson
authors.forename: Mark A
authors.initials: MA
authors.lastname: Brockman
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002986:Clinical Trials as Topic; D005260:Female; D015658:HIV Infections / Q000517:prevention & control / Q000635:transmission / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D063065:Organophosphonates / Q000008:administration & dosage / Q000494:pharmacology*; D010802:Phylogeny; D017422:Sequence Analysis, DNA; D000068698:Tenofovir; D014622:Vaginal Creams, Foams, and Jellies / Q000008:administration & dosage / Q000494:pharmacology*; D014779:Virus Replication; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000235:genetics; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000235:genetics
chemical_list: D019380:Anti-HIV Agents; D063065:Organophosphonates; D014622:Vaginal Creams, Foams, and Jellies; D054301:gag Gene Products, Human Immunodeficiency Virus; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1; D000068698:Tenofovir; D000225:Adenine