title: Failure of immunologic criteria to appropriately identify antiretroviral treatment failure in Uganda.
abstract: OBJECTIVE
  Most antiretroviral treatment program in resource-limited settings use immunologic or clinical monitoring to measure response to therapy and to decide when to change to a second-line regimen. Our objective was to evaluate immunologic failure criteria against gold standard virologic monitoring.
  
  
  METHODS
  Observational cohort.
  
  
  METHODS
  Participants enrolled in an antiretroviral treatment program in rural Uganda who had at least 6 months of follow-up were included in this analysis. Immunologic monitoring was performed by CD4 cell counts every 3 months during the first year, and every 6 months thereafter. HIV-1 viral loads were performed every 6 months.
  
  
  RESULTS
  A total of 1133 participants enrolled in the Rakai Health Sciences Program antiretroviral treatment program between June 2004 and September 2007 were followed for up to 44.4 months (median follow-up 20.2 months; IQR 12.4-29.5 months). WHO immunologic failure criteria were reached by 125 (11.0%) participants. A virologic failure endpoint defined as HIV-1 viral load more than 400 copies/ml on two measurements was reached by 112 participants (9.9%). Only 26 participants (2.3%) experienced both an immunologic and virologic failure endpoint (2 viral load > 400 copies/ml) during follow-up.
  
  
  CONCLUSIONS
  Immunologic failure criteria performed poorly in our setting and would have resulted in a substantial proportion of participants with suppressed HIV-1 viral load being switched unnecessarily. These criteria also lacked sensitivity to identify participants failing virologically. Periodic viral load measurements may be a better marker for treatment failure in our setting.
authors.affiliation: National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA. sjr@jhmi.edu
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Reynolds
authors.forename: Gertrude
authors.initials: G
authors.lastname: Nakigozi
authors.forename: Kevin
authors.initials: K
authors.lastname: Newell
authors.forename: Anthony
authors.initials: A
authors.lastname: Ndyanabo
authors.forename: Ronald
authors.initials: R
authors.lastname: Galiwongo
authors.forename: Iga
authors.initials: I
authors.lastname: Boaz
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Quinn
authors.forename: Ron
authors.initials: R
authors.lastname: Gray
authors.forename: Maria
authors.initials: M
authors.lastname: Wawer
authors.forename: David
authors.initials: D
authors.lastname: Serwadda
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D008297:Male; D017211:Treatment Failure; D014454:Uganda; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents