title: Rate of accumulation of thymidine analogue mutations in patients continuing to receive virologically failing regimens containing zidovudine or stavudine: implications for antiretroviral therapy programs in resource-limited settings.
abstract: BACKGROUND
  Because changes in antiretroviral therapy in resource-limited settings (RLSs) are delayed until patients experience immunological or clinical failure, it is important to be able to estimate the consequences in terms of accumulation of thymidine analogue (TA) mutations (TAMs).
  
  
  METHODS
  The study included patients in EuroSIDA with 2 available genotypic resistance tests (GRTs) (human immunodeficiency virus [HIV] RNA level, >500 copies/mL in any measure between tests), provided that the first GRT was performed after the first virological failure of a TA and that the same TA was continued until the second GRT.
  
  
  RESULTS
  At the time of the first GRT in a pair (t0), 1 year after virological failure, a median of 3 TAMs were detected, mutations 41L and 215Y in 65% of pairs and 67N in 52%. Overall, 126 TAMs were accumulated during 548 person-years of follow-up (PYFUs) (1/4.3 years; 95% confidence interval, 3.7-5.0 years). Greater predicted activity of the TA at t0, TAM profile 2 (TAM2; vs TAM profile 1 [TAM1]) profiles at t0, use of a nonnucleoside reverse-transcriptase inhibitor (NNRTI) at t0 (vs combined NNRTI and protease inhibitor), and acquisition of HIV infection through heterosexual (vs homosexual) contacts were associated with a faster rate of TAM accumulation.
  
  
  CONCLUSIONS
  Although the estimated rate of TAM accumulation was lower than anticipated, all possible efforts should be continued to increase the availability of drug options in RLSs.
authors: Research Department of Infection and Population Health, Royal Free and University College Medical School, London, United Kingdom. a.cozzi-lepri@pcps.ucl.ac.uk
authors: Alessandro
authors: A
authors: Cozzi-Lepri
authors: Andrew N
authors: AN
authors: Phillips
authors: Javier
authors: J
authors: Martinez-Picado
authors: Antonella d'Arminio
authors: Ad
authors: Monforte
authors: Christine
authors: C
authors: Katlama
authors: Ann-Brit
authors: AB
authors: Eg Hansen
authors: Andrzej
authors: A
authors: Horban
authors: Johann
authors: J
authors: Bruun
authors: Bonaventura
authors: B
authors: Clotet
authors: Jens D
authors: JD
authors: Lundgren
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D024882:Drug Resistance, Viral; D005260:Female; D006678:HIV / Q000187:drug effects* / Q000235:genetics; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests / Q000379:methods; D008875:Middle Aged; D020125:Mutation, Missense; D018119:Stavudine / Q000627:therapeutic use*; D055815:Young Adult; D015215:Zidovudine / Q000627:therapeutic use*
chemical_list: D019380:Anti-HIV Agents; D015215:Zidovudine; D018119:Stavudine