title: Prevalence of HIV type-1 drug-associated mutations in pre-therapy patients in the Free State, South Africa.
abstract: BACKGROUND
  We aimed to characterize the molecular epidemiology of HIV type-1 (HIV-1) and the prevalence of drug-associated mutations prior to initiating highly active antiretroviral therapy (HAART) in the Free State province, South Africa. The Free State has a population of 3 million, an antenatal HIV prevalence of approximately 34% and a well established infrastucture for antiretroviral (ARV) provision.
  
  
  METHODS
  HIV-1 polymerase genes were sequenced from 425 HAART-naive HIV-1-positive patients at voluntary primary healthcare HIV testing centres, who were subsequently attending district centres for assessment for commencing ARVs. Patients (>18 years) were sampled randomly with no exclusion for gender or clinical criteria. Sequences were analysed according to phylogeny and drug resistance.
  
  
  RESULTS
  Phylogenetic clustering within the cohort was suggestive of multiple introductions of subtype C virus into the region. Drug resistance mutations (according to the International AIDS Society-USA classification) were distributed randomly across the cohort phylogeny with an overall prevalence of 2.3% in the sampled patients. When stratified according to CD4(+) T-cell count, the prevalence of resistance was 3.6%, 0.9% and 1.2% for CD4(+) T-cell counts <100, 200-350 and >500 cells/microl, respectively, and was most common for non-nucleoside reverse transcriptase inhibitor resistance (3.1% in patients with CD4(+) T-cell count <100 cells/microl). We surveyed all drug-selected mutations and found further significant clustering among patients with low CD4(+) T-cell counts (P=0.003), suggesting unrecognized exposure to ARVs.
  
  
  CONCLUSIONS
  In the Free State population, there was a statistical association between low CD4(+) T-cell counts and drug-associated viral polymorphisms. Our data advocate the benefit of detailed history taking from patients starting HAART at low CD4(+) T-cell counts with close follow-up of the virological response.
authors.affiliation: Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, Oxford University, Oxford, UK.
authors.forename: Kuan-Hsiang Gary
authors.initials: KH
authors.lastname: Huang
authors.forename: Dominique
authors.initials: D
authors.lastname: Goedhals
authors.forename: Helen
authors.initials: H
authors.lastname: Fryer
authors.forename: Cloete
authors.initials: C
authors.lastname: van Vuuren
authors.forename: Aris
authors.initials: A
authors.lastname: Katzourakis
authors.forename: Tulio
authors.initials: T
authors.lastname: De Oliveira
authors.forename: Helen
authors.initials: H
authors.lastname: Brown
authors.forename: Sharon
authors.initials: S
authors.lastname: Cassol
authors.forename: Chris
authors.initials: C
authors.lastname: Seebregts
authors.forename: Angela
authors.initials: A
authors.lastname: McLean
authors.forename: Paul
authors.initials: P
authors.lastname: Klenerman
authors.forename: Rodney
authors.initials: R
authors.lastname: Phillips
authors.forename: John
authors.initials: J
authors.lastname: Frater
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D024921:Drug Resistance, Multiple, Viral / Q000235:genetics*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000453:epidemiology* / Q000276:immunology; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D015995:Prevalence; D012367:RNA, Viral / Q000032:analysis / Q000235:genetics; D013019:South Africa / Q000453:epidemiology
chemical_list: D012367:RNA, Viral