title: Drug resistance mutations from whole blood proviral DNA among patients on antiretroviral drugs in Zimbabwe.
abstract: BACKGROUND
  There are more than 500 000 HIV-infected people on antiretroviral treatment (ART) in Zimbabwe with very limited laboratory monitoring. To ensure effective treatment and prevent transmission of drug resistance, affordable treatment monitoring is needed to guide individual treatment.
  
  
  METHODS
  125 whole blood samples from patients on first-line ART were investigated for drug resistance mutations using an in-house genotypic testing method. Patients had been on HIV reverse transcriptase inhibitors only, with some having been on both HIV and TB treatment. DNA was extracted from whole blood; amplicons were generated by nested PCR and sequenced. Drug resistance mutations were determined using the Stanford HIV drug resistance database. Exact statistics were used to investigate relationships between drug resistance and predisposing factors.
  
  
  RESULTS
  From 125 samples, 108 were successfully analyzed for drug resistance mutations. 11 of the 108 sequences had drug resistance mutations; predominantly M184V and Y181C. For a 100-cell increase in CD4 count, the odds of being resistant were 61% lower than those with the baseline CD4 count (p = 0.04, CI: 0.34-0.98). There was no association between concurrent HIV/TB treatment and drug resistance (p = 0.41).
  
  
  CONCLUSIONS
  Although plasma samples are recommended for genotypic testing, the cost of analyzing plasma RNA makes it less feasible in resource limited settings. Lower cost DNA drug resistance testing from whole blood samples was assessed as a treatment-monitoring tool among patients followed by CD4 and clinical monitoring only. The infrequent detection of resistance and higher CD4 is consistent with effective first-line treatment. Further investigation of proviral DNA as a tool to identify drug resistance mutations is warranted.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Chimukangara
authors.forename: Lovemore
authors.initials: L
authors.lastname: Gwanzura
authors.forename: Rebecca
authors.initials: R
authors.lastname: Mitchell
authors.forename: David
authors.initials: D
authors.lastname: Katzenstein
authors.affiliation: African Institute of Biomedical Science and Technology, 211 Dominion House, Cnr H. Chitepo and Parklane, Harare, Zimbabwe. benjiechim@yahoo.com.
authors.forename: Collen
authors.initials: C
authors.lastname: Masimirembwa
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012044:Regression Analysis; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D055815:Young Adult; D015030:Zimbabwe
chemical_list: D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase