The impact of daily cotrimoxazole prophylaxis and antiretroviral therapy on mortality and hospital admissions in HIV-infected Zambian children
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.
- SourceAvailable from: Martin WG Brinkhof
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- "As in other African cohorts, children started ART with advanced disease and median WAZ and HAZ scores at ART initiation were also similar to previous studies (Arrive et al. 2008; Bandyopadhyay & Bhattacharyya 2008; Sutcliffe et al. 2008). Other studies in Africa also showed an increase in WAZ and HAZ (Fassinou et al. 2004; Song et al. 2007; Walker et al. 2007; Wamalwa et al. 2007) without reaching normal values. In our study, this was also the case, despite observing growth over an extended period of time. "
ABSTRACT: Malnutrition is common in HIV-infected children in Africa and an indication for antiretroviral treatment (ART). We examined anthropometric status and response to ART in children treated at a large public-sector clinic in Malawi. All children aged <15 years who started ART between January 2001 and December 2006 were included and followed until March 2008. Weight and height were measured at regular intervals from 1 year before to 2 years after the start of ART. Sex- and age-standardized z-scores were calculated for weight-for-age (WAZ) and height-for-age (HAZ). Predictors of growth were identified in multivariable mixed-effect models. A total of 497 children started ART and were followed for 972 person-years. Median age (interquartile range; IQR) was 8 years (4-11 years). Most children were underweight (52% of children), stunted (69%), in advanced clinical stages (94% in WHO stages 3 or 4) and had severe immunodeficiency (77%). After starting ART, median (IQR) WAZ and HAZ increased from -2.1 (-2.7 to -1.3) and -2.6 (-3.6 to -1.8) to -1.4 (-2.1 to -0.8) and -1.8 (-2.4 to -1.1) at 24 months, respectively (P < 0.001). In multivariable models, baseline WAZ and HAZ scores were the most important determinants of growth trajectories on ART. Despite a sustained growth response to ART among children remaining on therapy, normal values were not reached. Interventions leading to earlier HIV diagnosis and initiation of treatment could improve growth response.Tropical Medicine & International Health 08/2010; 15(8):934-44. DOI:10.1111/j.1365-3156.2010.02561.x · 2.30 Impact Factor
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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). "
ABSTRACT: There are 2.1 million children under the age of 15 living with HIV/AIDS, and 290,000 children died of AIDS in 2007. Despite recent increases in the number of adults on antiretroviral therapy (ART), the number of children receiving treatment remains inappropriately small, and prevention of mother to child transmission (PMTCT) efforts have been grossly inadequate. In sub-Saharan Africa, 14% of those in need of treatment are children, but only 6% of those are receiving treatment. Globally, only 23% of HIV-positive pregnant women have access to PMTCT programmes, which led to 420,000 new pediatric infections last year. Countries with comprehensive, integrated family-centred care programmes are better equipped to prevent and treat pediatric HIV/AIDS. True family-centred care offers prompt maternal and pediatric HIV diagnosis, antiretroviral prophylaxis, cotrimoxazole prophylaxis, and long-term ART for the entire family, as appropriate. Simple child health interventions, prompt treatment of opportunistic infections, nutritional supplementation and infant replacement feeding, as well as malaria treatment and prevention have been proven to synergistically improve pediatric HIV care and increase service uptake. To eliminate pediatric HIV/AIDS, national governments must embrace family-centred care, implement pediatric-friendly infrastructure, and train healthcare workers to treat children.Global Public Health 07/2009; 4(4):386-401. DOI:10.1080/17441690802638725 · 0.92 Impact Factor
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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). "
ABSTRACT: To determine predictors of mortality in children on anti-retroviral therapy (ART) who attended the Paediatric HIV Clinic at Kamuzu Central Hospital in Lilongwe, Malawi. Retrospective case cohort study by chart review of children who had started ART between October 2004 and May 2006. Bivariable and multivariable analysis were performed with and without defaulters to evaluate associations according to vital status and to identify independent predictors of mortality. Forty-one of 258 children (15.9%) were deceased, 185 (71.7%) were alive, and 32 (12.4%) had defaulted: 51% were female, 7% were under 18 months, 26% were 18 months to 5 years, and 54% were >5 years of age. Most were WHO stage III or IV (56% and 37%, respectively). On multivariate analysis, factors most strongly associated with mortality and defaulting were age <18 months [hazards ratio (HR) 2.11 (95% CI 1.0-4.51)] and WHO stage IV [HR 2.00 (95% CI 1.07-3.76)]. To improve outcomes of HIV-positive children, they must be identified and treated early, specifically children under 18 months of age. Access to infant diagnostic procedures must be improved to allow effective initiation of ART in infants at higher risk of death.Tropical Medicine & International Health 07/2009; 14(8):862-9. DOI:10.1111/j.1365-3156.2009.02315.x · 2.30 Impact Factor