Adherence to Both Cotrimoxazole and Placebo is Associated with Improved Survival Among HIV-Infected Zambian Children
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In the CHAP randomized placebo-controlled trial of cotrimoxazole prophylaxis in HIV-infected Zambian children conducted between 2001 and 2003, cotrimoxazole was associated with significant mortality reductions. In a secondary analysis we used Cox regression models to estimate the association between adherence measured by bottle weights and caregiver report and subsequent mortality in children surviving >28 days (n = 496, 153 deaths). Adherence was high and similar in both cotrimoxazole and placebo groups; adherence from bottle weights was 100% at 71% of visits, while caregivers reported 100% adherence at 79% of visits. Every 10% lower adherence to cotrimoxazole or placebo measured by bottle weights was associated with a 10–11% increase in mortality risk. Effects remained after adjustment for baseline predictors of survival and for current and recent change in primary caregiver. Caregiver-reported adherence was not associated with survival. The association between bottle-weight adherence to placebo and survival is likely capturing unmeasured caregiver effects, whose identification will be essential for quantifying the impact of antiretroviral therapy (ART) adherence on clinical outcomes in children.
KeywordsHIV Africa Adherence Cotrimoxazole
We would like to thank the families and children enrolled in the CHAP trial. We also acknowledge Laura Farrelly, Nicola Kaganson and Patrick Phillips who organised adherence measurements in the trial and carried out initial exploratory analyses.
Sources of Support
The CHAP trial was funded by the Department for International Development, UK.
Cotrimoxazole and matching placebo suspension were provided by Interchem Ltd, Lusaka, and quality was tested at the Quality Control North West, Liverpool, UK.
The CHAP Trial Team
University Teaching Hospital, Lusaka, Zambia: Principal Investigators (Prof Chifumbe Chintu, Prof Ganapati Bhat), Project Management/Paediatricians (Dr Veronica Mulenga, Dr Kennedy Lishimpi, Dr Frederick Sinyinza, Dr Desire Kabamba), Microbiology (James Mwansa, Darlington Mwenya, Mr Mutela), Clinic Staff (Regina Chileshe, Catherine Kalengo, J Kaluwaji, Agness Simuchoba, Mrs Mutengo, Violet Bwalya, Mr Chitambala, Terence Chipoya, Betty Chanda), Data Management (Mwaka Choongo, Liffer Namakube, Paul Mutale), Virology (Gina Mulundu, Mrs Liwewe), Parasitology (Mr Mandanda), Pathology (Mr Mudenda).
Medical Research Council Clinical Trials Unit, London: Principal Investigators (Dr Di Gibb, Prof Andrew Nunn), Project/Data Management (Laura Farrelly, Nicola Kaganson, Dr Julia Abernethy, Dr Margaret Thomason, Alexander Ferrier), Statisticians (Prof Andrew Nunn, Dr Sarah Walker, Dr Deborah Ford).
Royal Free Hospital, London: Microbiology (Prof Stephen Gillespie, Sushma Patel, Claire Ling).
University College London: Principal Investigators (Prof Ali Zumla).
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