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Effect of cotrimoxazole on causes of death, hospital admissions and antibiotic use in HIV-infected children

Mulenga, Veronicaa; Ford, Deborahb; Walker, A Sarahb; Mwenya, Darlingtona; Mwansa, Jamesa; Sinyinza, Fredericka; Lishimpi, Kennedya; Nunn, Andrewb; Gillespie, Stephenc; Zumla, Alid; Chintu, Chifumbea; Gibb, Diana Mb; the CHAP Trial Team

doi: 10.1097/QAD.0b013e3280114ed7
Epidemiology and Social

Background: Cotrimoxazole prophylaxis reduces morbidity and mortality in HIV-1-infected children, but mechanisms for these benefits are unclear.

Methods: CHAP was a randomized trial comparing cotrimoxazole prophylaxis with placebo in HIV-infected children in Zambia where background bacterial resistance to cotrimoxazole is high. We compared causes of mortality and hospital admissions, and antibiotic use between randomized groups.

Results: Of 534 children (median age, 4.4 years; 32% 1–2 years), 186 died and 166 had one or more hospital admissions not ending in death. Cotrimoxazole prophylaxis was associated with lower mortality, both outside hospital (P = 0.01) and following hospital admission (P = 0.005). The largest excess of hospital deaths in the placebo group was from respiratory infections [22/56 (39%) placebo versus 10/35 (29%) cotrimoxazole]. By 2 years, the cumulative probability of dying in hospital from a serious bacterial infection (predominantly pneumonia) was 7% on cotrimoxazole and 12% on placebo (P = 0.08). There was a trend towards lower admission rates for serious bacterial infections in the cotrimoxazole group (19.1 per 100 child-years at risk versus 28.5 in the placebo group, P = 0.09). Despite less total follow-up due to higher mortality, more antibiotics (particularly penicillin) were prescribed in the placebo group in year one [6083 compared to 4972 days in the cotrimoxazole group (P = 0.05)].

Conclusions: Cotrimoxazole prophylaxis appears to mainly reduce death and hospital admissions from respiratory infections, supported further by lower rates of antibiotic prescribing. As such infections occur at high CD4 cell counts and are common in Africa, the role of continuing cotrimoxazole prophylaxis after starting antiretroviral therapy requires investigation.

From the aUniversity Teaching Hospital, Lusaka, Zambia

bMRC Clinical Trials Unit, London

cRoyal Free Hospital, London

dUniversity College London, London, UK.

*See Appendix.

Received 7 June, 2006

Revised 25 August, 2006

Accepted 26 September, 2006

Correspondence to Dr A Sarah Walker, Medical Research Council Clinical Trials Unit, 222 Euston Road, London NW1 2DA, UK. E-mail:

© 2007 Lippincott Williams & Wilkins, Inc.