Outcomes after virologic failure of first-line ART in South Africa

Richard A. Murphy, Henry Sunpath, Zhigang Lu, Neville Chelin, Elena Losina, Michelle Gordon, Douglas Ross, Aba D. Ewusi, Lynn T. Matthews, Daniel R. Kuritzkes, Vincent C. Marconi

Research output: Contribution to journalArticlepeer-review

56 Scopus citations


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/μl 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/μl and the mortality was 6%. The median CD4 cell count at initial virologic failure among those who died was 70 cells/μl, compared to 182 cells/μl 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.

Original languageEnglish (US)
Pages (from-to)1007-1012
Number of pages6
Issue number7
StatePublished - Apr 2010
Externally publishedYes


  • HIV-1 drug resistance
  • Resource-limited settings
  • Second-line antiretroviral therapy
  • South Africa
  • Virologic failure

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases


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