Cotrimoxazole prophylaxis for opportunistic infections in children with HIV infection

Abstract
The majority of children with HIV infection live in low-income countries without access to antiretroviral drugs. The prevention and early treatment of opportunistic infections are the mainstay of their medical management. Cotrimoxazole is cheap and effective against a wide range of organisms, including Pneumocystis jiroveci pneumonia (PCP), which is an important cause of death and illness in the first year of life. It is safe with relatively few side effects. Diagnosis of HIV in children is complicated by the presence of maternal antibodies in early life. Providing prophylaxis based initially on maternal status is one possible solution. However, routine prophylactic treatment is difficult to deliver in low-resource settings, and could also lead to increased resistance to the drug. To assess the effects of routinely administered cotrimoxazole on death and illness episodes in children with HIV infection, and in infants of HIV-infected mothers. We searched the Cochrane HIV/AIDS registry, MEDLINE, the Cochrane Controlled Trials Register, LILACS, AIDSLINE, AIDSTRIALS and AIDSDRUGS databases, and proceedings and abstracts from AIDS and TB conferences (search date Feb 2005). We checked reference lists of pertinent articles, and contacted pharmaceutical companies and experts in the field. Randomised or quasi-randomised trials comparing routinely administered cotrimoxazole versus placebo or no treatment in children (age less than 15 years) with HIV infection, or children less than 18 months with HIV infected mothers. Two reviewers independently assessed trial eligibility and quality. Where data were incomplete or unclear trial authors were contacted for further details. One study was identified that fulfilled the inclusion criteria. It studied 534 children with HIV infection in Lusaka, Zambia. The study was conducted in an area of high bacterial resistance to cotrimoxazole (60-80%). A reduction in mortality of 33% was seen in the cotrimoxazole group as compared to placebo, relative risk 0.67 (95% CI 0.53 - 0.85). There was also a beneficial effect on hospitalisation, relative risk 0.77 (95% CI 0.62 - 0.96). There was no difference in adverse events between groups, and the beneficial effect was seen across all ages and CD4%. A single trial has shown a beneficial effect from the use of cotrimoxazole prophylaxis in HIV infected children in Zambia. It must be decided whether this can be extrapolated to other resource-poor settings.