title: Outcomes after virologic failure of first-line ART in South Africa.
abstract: OBJECTIVE
  To determine initial 24-week outcomes among prospectively enrolled patients with failure of initial antiretroviral therapy (ART).
  
  
  METHODS
  Baseline virologic failure was defined as HIV-1 viral load greater than 1000 copies/ml. Second-line ART was informed by results of genotype testing and selected from agents in the South-African public sector. Twenty-four week endpoints included virologic suppression and mortality.
  
  
  RESULTS
  The cohort consisted of 141 patients (median CD4 cell count and viral load at failure of 173 cells/microl and 17 500 copies/ml). The median prior duration of initial ART was 12.0 months. At least one major resistance mutation was found in 87% of patients. After 24 weeks of follow-up, intent-to-treat virologic suppression (<50 copies/ml) was 65%, as-treated virologic suppression was 78%, the median CD4 cell count improvement was 88 cells/microl and the mortality was 6%. The median CD4 cell count at initial virologic failure among those who died was 70 cells/microl, compared to 182 cells/microl among patients who survived (P = 0.01). Patients with wild-type virus at initial failure (N = 19) had inferior outcomes after switch. The presence of nucleoside analogue resistance mutations at failure did not affect early efficacy of boosted-protease inhibitor regimens.
  
  
  CONCLUSIONS
  Virologic monitoring linked to resistance testing helped demonstrate the efficacy of lopinavir/ritonavir-containing second-line regimens in South Africa. A switch to second-line regimens in patients with virologic failure and drug resistance has substantial and rapid immunological and clinical benefits. Resistance testing identified a high-risk group without resistance who might benefit from increased medication access and/or adherence support.
authors.affiliation: Operational Support Unit, Doctors Without Borders, New York, New York 10001, USA. ramurphy@gmail.com
authors.forename: Richard A
authors.initials: RA
authors.lastname: Murphy
authors.forename: Henry
authors.initials: H
authors.lastname: Sunpath
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Lu
authors.forename: Neville
authors.initials: N
authors.lastname: Chelin
authors.forename: Elena
authors.initials: E
authors.lastname: Losina
authors.forename: Michelle
authors.initials: M
authors.lastname: Gordon
authors.forename: Douglas
authors.initials: D
authors.lastname: Ross
authors.forename: Aba D
authors.initials: AD
authors.lastname: Ewusi
authors.forename: Lynn T
authors.initials: LT
authors.lastname: Matthews
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Kuritzkes
authors.forename: Vincent C
authors.initials: VC
authors.lastname: Marconi
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011446:Prospective Studies; D013019:South Africa; D017211:Treatment Failure; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D044966:Anti-Retroviral Agents
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