The impact of daily cotrimoxazole prophylaxis and antiretroviral therapy on mortality and hospital admissions in HIV-infected Zambian children

MRC Clinical Trials Unit, London, United Kingdom.
Clinical Infectious Diseases (Impact Factor: 9.42). 06/2007; 44(10):1361-7. DOI: 10.1086/515396
Source: PubMed

ABSTRACT Data on the population effectiveness of cotrimoxazole prophylaxis and antiretroviral therapy (ART) in human immunodeficiency virus (HIV)-infected African children are few.
A total of 534 Zambian children with HIV infection were randomized to receive daily cotrimoxazole prophylaxis or placebo in the Children with HIV Antibiotic Prophylaxis trial. Following trial closure, children who received the placebo initiated cotrimoxazole prophylaxis, and all children were observed in a closed cohort. Mortality and hospital admission rates were compared, over calendar time, in 9-month periods: trial recruitment (March 2001 to April 2002, May 2002 to January 2003), trial follow-up to closure (February 2003 to October 2003), initial follow-up posttrial (November 2003 to July 2004), and early and later ART availability (August 2004 to April 2005, and May 2005 to May 2006, respectively).
A total of 546 child-years of follow-up, 40 deaths, and 80 hospital admissions were observed between the time of trial closure and June 2006. A total of 117 of 283 children who were alive at trial closure received ART in the posttrial period (median child age at first use of ART, 8.8 years). Rates decreased in both groups during the trial period, suggesting a survivorship effect. Mortality and hospital admission rates before trial closure were 14 (95% confidence interval [CI], 9-21) deaths per 100 child-years and 24 (95% CI, 15-39) hospital admissions per 100 child-years, respectively, for children who were receiving cotrimoxazole, and were 23 (95% CI, 16-34) deaths per 100 child-years and 35 (95% CI, 23-53) hospital admissions per 100 child-years, respectively, for children who were receiving the placebo. After trial closure, rates remained stable in the cotrimoxazole group, but decreased to 15 (95% CI, 8-26) deaths per 100 child-years and 19 (95% CI, 10-41) hospital admissions per 100 child-years, respectively, for the group of children who received placebo and then initiated cotrimoxazole prophylaxis. In both groups combined, mortality rates decreased to 6 (95% CI, 3-11) deaths per 100 child-years and then 2 (95% CI, 0.8-6) deaths per 100 child-years during periods of ART availability; hospital admission rates decreased to 17 (95% CI, 11-27) hospital admissions per 100 child-years and 8 (95% CI, 4-15) hospital admissions per 100 child-years, respectively.
The benefits of once-daily cotrimoxazole prophylaxis continued throughout the trial and after trial closure. Mortality and hospital admissions decreased (by approximately 6-fold and approximately 3-fold, respectively) following ART availability, similar to findings observed in resource-rich countries.

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    • "Because of better case finding of families living with HIV, family-centred clinics are able to locate HIV-exposed children earlier, so they can receive cotrimoxazole sooner. Given in this fashion, cotrimoxazole prophylaxis can reduce mortality by up to 50% at an average cost of just $3Á5 per child per year (Chintu et al. 2004, Walker et al. 2007). Moreover, it is also an effective prophylaxis against malarial coinfections (Mermin et al. 2005) and can actually decrease malaria transmission within families with several HIV-positive members (Mermin et al. 2005, Mermin et al. 2006). "
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    • "Approximately 10–15% of individuals die within 15 months of ART initiation, most within the first 3 months (Etard et al. 2006; Zachariah et al. 2006; Zijlstra & van Oosterhout 2006; Callens et al. 2009). Among adults on ART, anaemia, low body mass index, low CD4 count (<50) or advanced WHO staging (IV), and Kaposi's sarcoma predict mortality (Zachariah et al. 2006; Boyd & Cooper 2007; Walker et al. 2007). In children younger than 15 years, WHO stage IV, severe wasting, low total lymphocyte count, and low CD4 count and percentage appear to contribute to early mortality (HIV Paediatric Prognostic Markers Collaborative Study 2005; Bolton-Moore et al. 2007; Bong et al. 2007; Kiboneka et al. 2008). "
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