title: High rate of K65R for antiretroviral therapy-naive patients with subtype C HIV infection failing a tenofovir-containing first-line regimen.
abstract: OBJECTIVE
  We sought to determine the rate of the K65R mutation in patients receiving tenofovir (TDF)-based antiretroviral therapy (ART) with subtype C HIV infection.
  
  
  METHODS
  Retrospective cohort study.
  
  
  METHODS
  All patients initiated on stavudine (d4T) with lamivudine (3TC) or TDF with 3TC and a nonnucleoside reverse transcriptase inhibitor at McCord Hospital in Durban, South Africa had their charts reviewed. All patients with virologic failure, defined as a viral load more than 1000 copies/ml after 5 months of a first ART regimen, had genotypic resistance testing performed prospectively using a validated in-house assay. Important resistance mutations were selected based upon published mutations in subtype B virus in the Stanford HIV Drug Resistance database.
  
  
  RESULTS
  A total of 585 patients were initiated on TDF-containing first-line ART from 3 August 2010 to 17 March 2011. Thirty-five (6.0%) of these patients had virologic failure and 23 of 33 (69.7%) of the virologic failure patients had the K65R mutation. The median (interquartile range) for the baseline CD4 cell count was 105 cells/μl (49-209) and viral load at virologic failure was 47 571 copies/ml (20 708-202 000). During the same period, 53 patients were initiated on d4T-containing regimens. Two (3.8%) of these patients had virologic failure and one of the virologic failure patients had the K65R mutation.
  
  
  CONCLUSIONS
  Preliminary data show very high rates (>65%) of K65R for patients failing TDF-based first-line regimens at McCord Hospital with few additional nucleoside reverse transcriptase inhibitor mutations compared with subtype B. These rates may reflect faster in-vivo selection, longer time on a failing regimen or transmitted drug resistance.
authors: McCord Hospital, Durban, South Africa. henrysunpath@yebo.co.za
authors: Henry
authors: H
authors: Sunpath
authors: Baohua
authors: B
authors: Wu
authors: Michelle
authors: M
authors: Gordon
authors: Jane
authors: J
authors: Hampton
authors: Brent
authors: B
authors: Johnson
authors: Mahomed-Yunus S
authors: MY
authors: Moosa
authors: Claudia
authors: C
authors: Ordonez
authors: Daniel R
authors: DR
authors: Kuritzkes
authors: Vincent C
authors: VC
authors: Marconi
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D001120:Arginine; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D024882:Drug Resistance, Viral / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D005260:Female; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors*; D006679:HIV Seropositivity / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D015497:HIV-1 / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use; D008239:Lysine; D008297:Male; D009154:Mutation; D063065:Organophosphonates / Q000627:therapeutic use*; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D013019:South Africa; D018119:Stavudine / Q000627:therapeutic use; D000068698:Tenofovir; D017211:Treatment Failure; D019562:Viral Load
chemical_list: D063065:Organophosphonates; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D001120:Arginine; D000068698:Tenofovir; D018119:Stavudine; D054303:HIV Reverse Transcriptase; D000225:Adenine; D008239:Lysine