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Cotrimoxazole may improve outcomes for children with HIV
Cotrimoxazole is now recommended by WHO as standard for pediatric patients with HIV.
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Mortality rates decreased sixfold and hospital admissions decreased threefold in children with HIV who received antiretroviral therapy, according to the findings of a study conducted in Zambia.
The researchers concluded that daily cotrimoxazole prophylaxis also reduced mortality rates in children who started the drug after the end of the Children with HIV Antibiotic Prophylaxis (CHAP) trial and before starting antiretroviral therapy (ART). Cotrimoxazole is now recommended by WHO as standard for pediatric patients with HIV living in resource-limited settings.
The findings corresponded with outcomes in children given ART in resource-rich countries. The study was a follow-up to the CHAP trial. It was conducted to compare outcomes in children in resource-poor areas with children in developed nations who received both ART and cotrimoxazole.
“We also know that cotrimoxazole has quite long-term benefits for children before starting ART and in areas with high background resistance of bacteria to the drug,” said Diana M. Gibb, MD, a professor of epidemiology and a pediatrician with the Medical Research Council Clinical Trials Unit in London.
“We saw a similar benefit from ART in the children as we did in children in the West,” Gibb told Infectious Disease News.
Gibb and colleagues published the findings of their study in Clinical Infectious Diseases.
Children with HIV
Malnutrition, overcrowded hospitals, late presentation and difficulty obtaining and transporting pediatric medications exacerbate mortality and comorbidities for children with HIV in Africa.
“Children with HIV and malnutrition have high mortality as an independent marker of HIV,” Gibb said.
Malnutrition and ART management in children requires more work, she added.
Children with HIV infection (n=534) were randomly assigned daily cotrimoxazole or placebo. All were enrolled in the CHAP trial in Lusaka, Zambia. The trial was closed early for efficacy because there was a 43% reduction in death rates and a 25% reduction in hospital rates in the cotrimoxazole group. These results were published in The Lancet in 2004 by Chintu, et al. After closure, all children in the placebo group started cotrimoxazole. Both groups were then observed as ART was introduced into Zambia.
Mortality and hospital admission rates were compared in nine-month periods at trial recruitment in March and April 2002, trial follow-up to closure from February to October 2003 and for initial follow-up post-trial from November 2003 to July 2004. Data from early ART availability from August 2004 to April 2005, and later ART availability from May 2005 to May 2006, were also used.
Median age at ART initiation was 8.8 years.
Mortality and hospitalization rates decreased in both groups. There were 40 deaths and 80 hospital admissions in the 546 child-years of follow-up between the time of trial closure in 2003 and June 2006.
One hundred seventeen of the 283 children who survived through the cotrimoxazole trial received ART in the post-trial period. In children receiving cotrimoxazole, mortality rates were 14 deaths per 100 child-years (95% CI) and hospital admission rates were 24 per 100 child-years (95% CI) before trial closure. Mortality rates were 23 deaths per 100 child-years (95% CI) and 35 hospital admissions per 100 child-years (95% CI) for children in the placebo group.
After trial closure, rates remained stable in the cotrimoxazole arm, but decreased to 15 deaths per 100 child-years (95% CI) and 19 hospital admissions per 100 child-years (95% CI) for the children in the placebo group who started cotrimoxazole. In both groups combined, mortality declined substantially during periods of ART availability.
Other studies presented earlier this year at the 14th Conference on Retroviruses and Opportunistic Infections in Los Angeles showed that giving cotrimoxazole prophylaxis was highly cost-effective to children. – by Kirsten H. Ellis
For more information:
- Walker AS, Mulenga V, Ford D, et al. The impact of daily cotrimoxazole prophylaxis and antiretroviral therapy on mortality and hospital admissions in HIV-infected Zambian children. Clin Infect Dis. 2007;444:1361-1367.