title: Resistance to tenofovir-based regimens during treatment failure of subtype C HIV-1 in South Africa.
abstract: BACKGROUND
  Tenofovir disoproxil fumarate (TDF) is increasingly available for patients infected with subtype C HIV-1. This subtype is reported to develop the principal TDF resistance mutation in the HIV reverse transcriptase, K65R, with greater propensity than other subtypes. We sought to describe K65R development during TDF use in a cohort of patients infected with subtype C HIV.
  
  
  METHODS
  Using a prospectively followed cohort with 6 monthly HIV RNA assays, we identified virological failure (defined as an HIV RNA > 1,000 copies/ml) during treatment that included TDF. Residual serum, stored at the time of the HIV RNA assay, was used for consensus sequencing and allele-specific PCR. We assessed prevalence of resistance at failure during TDF-containing treatment and associated factors.
  
  
  RESULTS
  Among 1,682 patients on a TDF-containing regimen, 270 developed failure of which 40 were assessed for resistance. By sequencing, the K65R was identified in 5 (12%), major non-nucleoside reverse transcriptase inhibitor mutations in 24 (57%) and the M184V/I in 12 (28%) patients. The K65R was associated with lower HIV RNA at failure (HIV RNA 3.3 versus 4.2 log10 copies/ml) and prior stavudine exposure. An additional five patients had minority K65R populations identified by allele-specific PCR.
  
  
  CONCLUSIONS
  These data suggest that the K65R prevalence at virological failure is moderately higher in our subtype C population than some non-subtype C HIV cohorts. However, we did not find that the K65R was highly selected in HIV-1 subtype-C-infected patients with up to 6 months of failure of a TDF-containing regimen.
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, MD, USA. choffmann@jhmi.edu.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Hoffmann
authors.forename: Johanna
authors.initials: J
authors.lastname: Ledwaba
authors.forename: Jin-Fen
authors.initials: JF
authors.lastname: Li
authors.forename: Victoria
authors.initials: V
authors.lastname: Johnston
authors.forename: Gillian
authors.initials: G
authors.lastname: Hunt
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Fielding
authors.forename: Richard E
authors.initials: RE
authors.lastname: Chaisson
authors.forename: Gavin J
authors.initials: GJ
authors.lastname: Churchyard
authors.forename: Alison D
authors.initials: AD
authors.lastname: Grant
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Johnson
authors.forename: Salome
authors.initials: S
authors.lastname: Charalambous
authors.forename: Lynn
authors.initials: L
authors.lastname: Morris
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D063065:Organophosphonates / Q000627:therapeutic use*; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D013019:South Africa; D000068698:Tenofovir; D017211:Treatment Failure; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D063065:Organophosphonates; D018894:Reverse Transcriptase Inhibitors; D000068698:Tenofovir; D000225:Adenine