title: Rates and predictors of failure of first-line antiretroviral therapy and switch to second-line ART in South Africa.
abstract: OBJECTIVE
  To measure rates and predictors of virologic failure and switch to second-line antiretroviral therapy (ART) in South Africa.
  
  
  METHODS
  : Observational cohort study.
  
  
  METHODS
  We included ART-naive adult patients initiated on public sector ART (January 2000 to July 2008) at 5 sites in South Africa who completed ≥6 months of follow-up. We estimated cumulative risk of virologic failure (viral load ≥400 copies/mL with confirmation above varying thresholds) and switching to second-line ART.
  
  
  RESULTS
  Nineteen thousand six hundred forty-five patients (29,935 person-years) had a median of 1.3 years of study follow-up (1.8 years on ART) and a median CD4 count of 93 (IQR: 39-155) cells per microliter at ART initiation. About 9.9% (4.5 per 100 person-years) failed ART in median 16 (IQR: 12-23) months since ART initiation, with median 2.7 months (IQR: 1.6-4.7) months between first elevated and confirmatory viral loads. By survival analysis, using a confirmatory threshold of 400 copies per milliliter, 16.9% [95% confidence interval (CI): 15.4% to 18.6%] failed by 5 years on ART, but only 7.8% (95% CI: 6.6% to 9.3%) using a threshold of 10,000. CD4 <25 versus 100-199 (adjusted HR: 1.60; 95% CI: 1.37 to 1.87), ART initiation viral load ≥1,000,000 versus <10,000, (1.32; 0.91 to 1.93), and 2+ gaps in care versus 0 (95% CI: 7.25; 4.95 to 10.6) were predictive of failure. Overall, 10.1% (95% CI: 9.0% to 11.4%) switched to second-line by 5 years on ART. Lower CD4 at failure and higher rate of CD4 decline were predictive of switch (decline 100% to 51% versus 25% to -25%, adjusted HR: 1.96; 95% CI: 1.35 to 2.85).
  
  
  CONCLUSIONS
  In resource-limited settings with viral load monitoring, virologic failure rates are highly sensitive to thresholds for confirmation. Despite clear guidelines there is considerable variability in switching failing patients, partially in response to immunologic status and postfailure evolution.
authors.affiliation: Center for Global Health and Development, Boston University, 801 Massachusetts Ave., Boston, MA 02118, USA. mfox@bu.edu
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Fox
authors.forename: Gilles Van
authors.initials: GV
authors.lastname: Cutsem
authors.forename: Janet
authors.initials: J
authors.lastname: Giddy
authors.forename: Mhairi
authors.initials: M
authors.lastname: Maskew
authors.forename: Olivia
authors.initials: O
authors.lastname: Keiser
authors.forename: Hans
authors.initials: H
authors.lastname: Prozesky
authors.forename: Robin
authors.initials: R
authors.lastname: Wood
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Hernán
authors.forename: Jonathan A C
authors.initials: JA
authors.lastname: Sterne
authors.forename: Matthias
authors.initials: M
authors.lastname: Egger
authors.forename: Andrew
authors.initials: A
authors.lastname: Boulle
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000494:pharmacology; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D015331:Cohort Studies; D024882:Drug Resistance, Viral; D005260:Female; D006678:HIV / Q000302:isolation & purification; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D018570:Risk Assessment; D013019:South Africa; D017211:Treatment Failure; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents