title: Virologic versus immunologic monitoring and the rate of accumulated genotypic resistance to first-line antiretroviral drugs in Uganda.
abstract: BACKGROUND
  Viral load monitoring (VLM) to identify individuals failing antiretroviral therapy (ART) is not widely available in resource-limited settings. We compared the genotypic resistance patterns between clients with VLM versus immunological monitoring (IM).
  
  
  METHODS
  Between 2004-2008, 559 ART naïve clients were enrolled in a prospective cohort, initiated on ART, and monitored with viral load (VL) and CD4+ cell counts every 6 months (VLM group). From February 2008 through June 2009, 998 clients on ART for 36-40 months (corresponding to the follow-up time of the VLM group) at the same clinic and monitored with CD4+ cell counts every 6 months were recruited into a cross sectional study (IM group). Samples from VLM clients at 12, 24 and 36 months and IM clients at 36-40 months with VL > 2000 copies/ml underwent genotypic drug resistance testing.
  
  
  RESULTS
  Baseline characteristics were similar. Virologic failure (VL > 400 copies/ml) at 12, 24 and 36 months in the VLM group were 12%, 6% and 8% respectively, and in the IM group 10% at 36-40 months. Samples from 39 VLM and 70 IM clients were genotyped. 23/39 (59%) clients in the VLM group (at 12, 24 or 36 months) compared to 63/70 (90%) in the IM group, (P < 0.0001) had at least 1 non-nucleoside reverse transcriptase mutation. 19/39 (49%) of VLM clients had an M184V mutation compared to 61/70 (87%) in the IM group (P < 0.0001). Only 2/39 (5%) of VLM clients developed thymidine analogue mutations compared to 34/70 (49%) of IM clients (P < 0.0001).
  
  
  CONCLUSIONS
  Routine VL monitoring reduced the rate of accumulated genotypic resistance to commonly used ART in Uganda.
authors.affiliation: Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. sjreynolds@niaid.nih.gov
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Reynolds
authors.forename: Hakim
authors.initials: H
authors.lastname: Sendagire
authors.forename: Kevin
authors.initials: K
authors.lastname: Newell
authors.forename: Barbara
authors.initials: B
authors.lastname: Castelnuovo
authors.forename: Immaculate
authors.initials: I
authors.lastname: Nankya
authors.forename: Moses
authors.initials: M
authors.lastname: Kamya
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Quinn
authors.forename: Yukari C
authors.initials: YC
authors.lastname: Manabe
authors.forename: Andrew
authors.initials: A
authors.lastname: Kambugu
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D015497:HIV-1 / Q000187:drug effects / Q000472:pathogenicity; D006801:Humans; D008297:Male; D011446:Prospective Studies; D014454:Uganda
chemical_list: D019380:Anti-HIV Agents