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Determinants of Survival Without Antiretroviral Therapy After Infancy in HIV-1-Infected Zambian Children in the CHAP Trial

Walker, A. Sarah PhD, MSc*; Mulenga, Veronica MD; Sinyinza, Frederick MD; Lishimpi, Kennedy MD; Nunn, Andrew MSc*; Chintu, Chifumbe MD, FRCPC, FRCP; Gibb, Diana M. MbChB, MD, MSc, FRCPCH*CHAP Trial Team

JAIDS Journal of Acquired Immune Deficiency Syndromes: August 15th, 2006 - Volume 42 - Issue 5 - p 637-645
doi: 10.1097/01.qai.0000226334.34717.dc
Epidemiology and Social Science

Background: There are few data on predictors of HIV progression in untreated children in resource-limited settings.

Methods: Children with HIV Antibiotic Prophylaxis (CHAP) was a randomized trial comparing cotrimoxazole prophylaxis with placebo in HIV-infected Zambian children. The prognostic value of baseline characteristics was investigated using Cox models.

Results: Five hundred fourteen children aged 1 to 14 (median 5.5) years contributed 607 years follow-up (maximum 2.6 years). Half were boys, and in 67%, the mother was the primary carer; at baseline, median CD4 percentage was 11% and weight was less than third percentile in 67%. One hundred sixty-five children died (27.2 per 100 years at risk; 95% confidence interval 23.3-31.6). Low weight-for-age, CD4 percentage, hemoglobin, mother as primary carer, current malnutrition, and previous hospital admissions for respiratory tract infections or recurrent severe bacterial infections were independent predictors of poorer survival, whereas oral candidiasis predicted poorer survival only when baseline CD4 percentage was not considered. Mortality rates per 100 child years of 44.5 (37.2-53.2), 14.7 (10.9-19.8), and 2.3 (0.3-16.7) were associated with new World Health Organization stages 4, 3, and 1/2, respectively, applied retrospectively; very low weight-for-age was the only staging feature for 42% of stage 4 children.

Conclusions: Malnutrition and hospitalizations for respiratory/bacterial infections predict mortality independent of immunosuppression, suggesting that they capture HIV- and non-HIV-related mortality, whereas oral candidiasis is a proxy for immunosuppression.

From the *MRC Clinical Trials Unit, London, UK; and the †University Teaching Hospital, Lusaka, Zambia, ‡A complete list of the members of the CHAP Trial Team appears at the end of this article.

Received for publication January 27, 2006; accepted April 10, 2006.

Sources of support: The CHAP trial was funded by the Department for International Development, UK.

Reprints: A. Sarah Walker, PhD, MSc, Medical Research Council Clinical Trials Unit, 222 Euston Road, London NW1 2DA, UK (e-mail: s.walker@ctu.mrc.ac.uk).

© 2006 Lippincott Williams & Wilkins, Inc.