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

Murphy, Richard Aa; Sunpath, Henryb; Lu, Zhigangc; Chelin, Nevilleb; Losina, Elenac; Gordon, Michelled; Ross, Douglase; Ewusi, Aba Df; Matthews, Lynn Tg; Kuritzkes, Daniel Rh; Marconi, Vincent Ci,j; for the South Africa Resistance Cohort Study Team

doi: 10.1097/QAD.0b013e3283333639
Clinical Science: Concise Communications

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.

aOperational Support Unit, Doctors Without Borders, New York, New York, USA

bMcCord Hospital, Durban, South Africa

cMassachusetts General Hospital, Boston, Massachusetts, USA

dNelson Mandela School of Medicine, Durban, South Africa

eSt. Mary's Hospital, Mariannhill, South Africa

fHarvard Medical School, USA

gDivision of Infectious Diseases, Beth Israel Deaconess Medical Center, USA

hSection of Retroviral Therapeutics, Brigham and Women's Hospital, Boston, Massachusetts, USA

iInfectious Disease Service, San Antonio Military Medical Center, Fort Sam Houston, Texas, USA

jEmory University School of Medicine, Atlanta, Georgia, USA.

Received 23 April, 2009

Revised 11 September, 2009

Accepted 18 September, 2009

Correspondence to Richard A. Murphy, MD, Doctors Without Borders/USA 333 7th Avenue, Second Floor, NY 10001, USA. E-mail:

© 2010 Lippincott Williams & Wilkins, Inc.