title: High-levels of acquired drug resistance in adult patients failing first-line antiretroviral therapy in a rural HIV treatment programme in KwaZulu-Natal, South Africa.
abstract: OBJECTIVE
  To determine the frequency and patterns of acquired antiretroviral drug resistance in a rural primary health care programme in South Africa.
  
  
  METHODS
  Cross-sectional study nested within HIV treatment programme.
  
  
  METHODS
  Adult (≥ 18 years) HIV-infected individuals initially treated with a first-line stavudine- or zidovudine-based antiretroviral therapy (ART) regimen and with evidence of virological failure (one viral load >1000 copies/ml) were enrolled from 17 rural primary health care clinics. Genotypic resistance testing was performed using the in-house SATuRN/Life Technologies system. Sequences were analysed and genotypic susceptibility scores (GSS) for standard second-line regimens were calculated using the Stanford HIVDB 6.0.5 algorithms.
  
  
  RESULTS
  A total of 222 adults were successfully genotyped for HIV drug resistance between December 2010 and March 2012. The most common regimens at time of genotype were stavudine, lamivudine and efavirenz (51%); and stavudine, lamivudine and nevirapine (24%). Median duration of ART was 42 months (interquartile range (IQR) 32-53) and median duration of antiretroviral failure was 27 months (IQR 17-40). One hundred and ninety one (86%) had at least one drug resistance mutation. For 34 individuals (15%), the GSS for the standard second-line regimen was <2, suggesting a significantly compromised regimen. In univariate analysis, individuals with a prior nucleoside reverse-transcriptase inhibitor (NRTI) substitution were more likely to have a GSS <2 than those on the same NRTIs throughout (odds ratio (OR) 5.70, 95% confidence interval (CI) 2.60-12.49).
  
  
  CONCLUSIONS
  There are high levels of drug resistance in adults with failure of first-line antiretroviral therapy in this rural primary health care programme. Standard second-line regimens could potentially have had reduced efficacy in about one in seven adults involved.
authors.affiliation: Africa Centre for Health and Population Studies, University of KwaZulu-Natal, Somkhele, South Africa.
authors.forename: Justen
authors.initials: J
authors.lastname: Manasa
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Lessells
authors.forename: Andrew
authors.initials: A
authors.lastname: Skingsley
authors.forename: Kevindra K
authors.initials: KK
authors.lastname: Naidu
authors.forename: Marie-Louise
authors.initials: ML
authors.lastname: Newell
authors.forename: Nuala
authors.initials: N
authors.lastname: McGrath
authors.forename: Tulio
authors.initials: T
authors.lastname: de Oliveira
mesh_terms: D000293:Adolescent; D000328:Adult; D000480:Alkynes; D000704:Analysis of Variance; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use*; D048588:Benzoxazines / Q000494:pharmacology / Q000627:therapeutic use; D003430:Cross-Sectional Studies; D003521:Cyclopropanes; D024882:Drug Resistance, Viral / Q000187:drug effects* / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009154:Mutation; D019829:Nevirapine / Q000494:pharmacology / Q000627:therapeutic use; D017063:Outcome Assessment, Health Care; D015995:Prevalence; D013019:South Africa / Q000453:epidemiology; D018119:Stavudine / Q000494:pharmacology / Q000627:therapeutic use; D055815:Young Adult; D015215:Zidovudine / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D019259:Lamivudine; D015215:Zidovudine; D019829:Nevirapine; D018119:Stavudine; C098320:efavirenz