Co-trimoxazole as prophylaxis against opportunistic infections in HIV-infected Zambian children (CHAP): a double-blind randomised placebo-controlled trial.

Abstract

BACKGROUND:

No trials of co-trimoxazole (trimethoprim-sulfamethoxazole) prophylaxis for HIV-infected adults or children have been done in areas with high levels of bacterial resistance to this antibiotic. We aimed to assess the efficacy of daily co-trimoxazole in such an area.

METHODS:

We did a double-blind randomised placebo-controlled trial in children aged 1-14 years with clinical features of HIV infection in Zambia. Primary outcomes were mortality and adverse events possibly related to treatment. Analysis was by intention to treat.

FINDINGS:

In October, 2003, the data and safety monitoring committee recommended early stopping of the trial. 541 children had been randomly assigned; seven were subsequently identified as HIV negative and excluded. After median follow-up of 19 months, 74 (28%) children in the co-trimoxazole group and 112 (42%) in the placebo group had died (hazard ratio [HR] 0.57 [95% CI 0.43-0.77], p=0.0002). This benefit applied in children followed up beyond 12 months (n=320, HR 0.48 [0.27-0.84], test for heterogeneity p=0.60) and across all ages (test for heterogeneity p=0.82) and baseline CD4 counts (test for heterogeneity p=0.36). 16 (6%) children in the co-trimoxazole group had grade 3 or 4 adverse events compared with 18 (7%) in the placebo group. These events included rash (one placebo), and a neutrophil count on one occasion less than 0.5x10(9)/L (16 [6%] co-trimoxazole vs seven [3%] placebo, p=0.06). Pneumocystis carinii was identified by immunofluorescence in only one (placebo) of 73 nasopharyngeal aspirates from children with pneumonia.

INTERPRETATION:

Our results suggest that children of all ages with clinical features of HIV infection should receive co-trimoxazole prophylaxis in resource-poor settings, irrespective of local resistance to this drug.

• Authors: C Chintu, G J Bhat, A S Walker, V Mulenga, F Sinyinza, K Lishimpi, L Farrelly, N Kaganson, A Zumla, S H Gillespie, A J Nunn, D M Gibb, CHAP trial team
• Journal: Lancet (London, England) (Lancet) 2004 Nov 20-26 Vol. 364 Issue 9448 Pg. 1865-71 ISSN: 1474-547X [Electronic] England
• PMID: 15555666 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Bacterial Agents
• Trimethoprim, Sulfamethoxazole Drug Combination

Topics

• AIDS-Related Opportunistic Infections (prevention & control)
• Anti-Bacterial Agents (adverse effects, therapeutic use)
• Antibiotic Prophylaxis
• Child
• Child, Preschool
• Double-Blind Method
• Female
• HIV Infections (mortality)
• Hospitalization
• Humans
• Infant
• Male
• Survival Rate
• Trimethoprim, Sulfamethoxazole Drug Combination (adverse effects, therapeutic use)
• Zambia