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Response to highly active antiretroviral therapy among severely immuno-compromised HIV-infected patients in Cambodia

Madec, Yoanna; Laureillard, Didierb,c; Pinoges, Loretxud; Fernandez, Marcelob,c; Prak, Naromb; Ngeth, Chanchhayab; Moeung, Sumanakb; Song, Sovannarab; Balkan, Sunac; Ferradini, Laurentd; Quillet, Catherineb,c; Fontanet, Arnauda

doi: 10.1097/QAD.0b013e328012c54f
Epidemiology and Social

Background: HAART efficacy was evaluated in a real-life setting in Phnom Penh (Médecins Sans Frontières programme) among severely immuno-compromised patients.

Methods: Factors associated with mortality and immune reconstitution were identified using Cox proportional hazards and logistic regression models, respectively.

Results: From July 2001 to April 2005, 1735 patients initiated HAART, with median CD4 cell count of 20 (inter-quartile range, 6–78) cells/μl. Mortality at 2 years increased as the CD4 cell count at HAART initiation decreased, (4.4, 4.5, 7.5 and 24.7% in patients with CD4 cell count > 100, 51–100, 21–50 and ≤ 20 cells/μl, respectively; P < 10−4). Cotrimoxazole and fluconazole prophylaxis were protective against mortality as long as CD4 cell counts remained ≤ 200 and ≤ 100 cells/μl, respectively. The proportion of patients with successful immune reconstitution (CD4 cell gain > 100 cells/μl at 6 months) was 46.3%; it was lower in patients with previous ART exposure [odds ratio (OR), 0.16; 95% confidence interval (CI), 0.05–0.45] and patients developing a new opportunistic infection/immune reconstitution infection syndromes (OR, 0.71; 95% CI, 0.52–0.98). Similar efficacy was found between the stavudine–lamivudine–nevirapine fixed dose combination and the combination stavudine–lamivudine–efavirenz in terms of mortality and successful immune reconstitution. No surrogate markers for CD4 cell change could be identified among total lymphocyte count, haemoglobin, weight and body mass index.

Conclusion: Although CD4 cell count-stratified mortality rates were similar to those observed in industrialized countries for patients with CD4 cell count > 50 cells/μl, patients with CD4 cell count ≤ 20 cells/μl posed a real challenge to clinicians. Widespread voluntary HIV testing and counselling should be encouraged to allow HAART initiation before the development of severe immuno-suppression.

From the aUnité d'Epidémiologie des Maladies Emergentes, Institut Pasteur, Paris, France

bInfectious Diseases Department, P.B.N Sihanouk Hospital, Phnom Penh, Cambodia

cMédecins Sans Frontières, Paris

dEpicentre, Paris, France.

Received 29 July, 2006

Revised 23 August, 2006

Accepted 3 October, 2006

Correspondence to Arnaud Fontanet, Institut Pasteur - Unité d'Epidémiologie des Maladies Emergentes, 25–28 rue du Docteur Roux, 75015 Paris, France. E-mail:

© 2007 Lippincott Williams & Wilkins, Inc.