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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 0.5 x 109/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. [ABSTRACT FROM AUTHOR]

A high level of adherence to antiretroviral treatment is essential for optimal clinical outcomes in HIV infection, but measuring adherence is difficult. We investigated whether responses to a questionnaire eliciting caregiver beliefs in medicines were associated with adherence of their child (median age 2.8 years), and whether this in turn was associated with viral suppression. We used the validated beliefs in medicine questionnaire (BMQ) to measure caregiver beliefs, and medication event monitoring system caps to measure adherence. We found significant associations between BMQ scores and adherence, and between adherence and viral suppression. Among children initiating Antiretroviral therapy (ART), we also found significant associations between BMQ 'necessity' scores, and BMQ 'necessity-concerns' scores, and later viral suppression. This suggests that the BMQ may be a valuable tool when used alongside other adherence measures, and that it remains important to keep caregivers well informed about the long-term necessity of their child's ART., Competing Interests: The authors declare no conflict of interest. Ethical Approval Approval for this study protocol was obtained from the Research Ethical Committees from UK, Zambia and Uganda. All study participants caregivers signed a written informed consent; in addition older children aware of their HIV status gave assent following research guidelines in Uganda and Zambia.

In the April 2010 issue of this journal, Date et al. expressed concern over the slow scale-up in low-income settings of two therapies for the prevention of opportunistic infections in people living with the human immunodeficiency virus: co-trimoxazole prophylaxis and isoniazid preventive therapy. This short paper discusses the important ways in which policy analysis can be of use in understanding and explaining how and why certain evidence makes its way into policy and practice and what local factors influence this process. Key lessons about policy development are drawn from the research evidence on co-trimoxazole prophylaxis, as such lessons may prove helpful to those who seek to influence the development of national policy on isoniazid preventive therapy and other treatments. Researchers are encouraged to disseminate their findings in a manner that is clear, but they must also pay attention to how structural, institutional and political factors shape policy development and implementation. Doing so will help them to understand and address the concerns raised by Date et al. and other experts. Mainstreaming policy analysis approaches that explain how local factors shape the uptake of research evidence can provide an additional tool for researchers who feel frustrated because their research findings have not made their way into policy and practice.