title: Virological efficacy and emergence of drug resistance in adults on antiretroviral treatment in rural Tanzania.
abstract: BACKGROUND
  Virological response to antiretroviral treatment (ART) in rural Africa is poorly described. We examined virological efficacy and emergence of drug resistance in adults receiving first-line ART for up to 4 years in rural Tanzania.
  
  
  METHODS
  Haydom Lutheran Hospital has provided ART to HIV-infected patients since October 2003. A combination of stavudine or zidovudine with lamivudine and either nevirapine or efavirenz is the standard first-line regimen. Nested in a longitudinal cohort study of patients consecutively starting ART, we carried out a cross-sectional virological efficacy survey between November 2007 and June 2008. HIV viral load was measured in all adults who had completed at least 6 months first-line ART, and genotypic resistance was determined in patients with viral load >1000 copies/mL.
  
  
  RESULTS
  Virological response was measured in 212 patients, of whom 158 (74.5%) were women, and median age was 35 years (interquartile range [IQR] 29-43). Median follow-up time was 22.3 months (IQR 14.0-29.9). Virological suppression, defined as <400 copies/mL, was observed in 187 patients (88.2%). Overall, prevalence of > or =1 clinically significant resistance mutation was 3.9, 8.4, 16.7 and 12.5% in patients receiving ART for 1, 2, 3 and 4 years, respectively. Among those successfully genotyped, the most frequent mutations were M184I/V (64%), conferring resistance to lamivudine, and K103N (27%), Y181C (27%) and G190A (27%), conferring resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs), whereas 23% had thymidine analogue mutations (TAMs), associated with cross-resistance to all nucleoside reverse transcriptase inhibitors (NRTIs). Dual-class resistance, i.e. resistance to both NRTIs and NNRTIs, was found in 64%.
  
  
  CONCLUSIONS
  Virological suppression rates were good up to 4 years after initiating ART in a rural Tanzanian hospital. However, drug resistance increased with time, and dual-class resistance was common, raising concerns about exhaustion of future antiretroviral drug options. This study might provide a useful forecast of drug resistance and demand for second-line antiretroviral drugs in rural Africa in the coming years.
authors: Ulleval Department of Infectious Diseases, Oslo University Hospital, Oslo, Norway. asgeir.johannessen@medisin.uio.no
authors: Asgeir
authors: A
authors: Johannessen
authors: Ezra
authors: E
authors: Naman
authors: Sokoine L
authors: SL
authors: Kivuyo
authors: Mabula J
authors: MJ
authors: Kasubi
authors: Mona
authors: M
authors: Holberg-Petersen
authors: Mecky I
authors: MI
authors: Matee
authors: Svein G
authors: SG
authors: Gundersen
authors: Johan N
authors: JN
authors: Bruun
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D008297:Male; D013636:Tanzania; D013997:Time Factors; D014766:Viremia / Q000188:drug therapy
chemical_list: D019380:Anti-HIV Agents