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鈥�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路57 [95% CI 0路43鈥�0路77], p=0路0002). This benefit applied in children followed up beyond 12 months (n=320, HR 0路48 [0路27鈥�0路84], test for heterogeneity p=0路60) and across all ages (test for heterogeneity p=0路82) and baseline CD4 counts (test for heterogeneity p=0路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路5脳109/L (16 [6%] co-trimoxazole vs seven [3%] placebo, p=0路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.
Citation
Chintu, C.; Bhat, G.J.; Walker, A.S.; Mulenga, V.; Sinyinza, F.; Lishimpi, K.; Farrelly, L.; Kangason, N.; Zumla, A.; Gillespie, S.H.; Nunn, A.J.; Gibb, D.M. Co-trimoxazole as prophylaxis against opportunistic infections in HIV-infected Zambian children (CHAP): a double-blind randomised placebo-controlled trial. Lancet (2004) 364 (9448) 1865-1871. [DOI: 10.1016/S0140-6736(04)17442-4]