AFISE Mortality and ART efficacy

Bristol-Myers Squibb Foundation Mortality and ART efficacy outcomes in children < 12 years on ART in Lesotho, Swaziland and Malawi Background The BIPAI Children’s Sub-Saharan Africa accounts for only 11% of the Clinical Centers world total population, yet over 60% of the world’s 1 of Excellence HIV infections occur in sub-Saharan Africa. For more than 10 years, the means to reduce the vertical Network transmission of the HIV virus from mother to child has been available yet for more than ten years the number of new paediatric HIV infections has 2 continued to rise at a precipitous rate. Benghazi, Libya Kampala, Uganda Kisumu, Kenya Mwanza, Tanzania Mbeya, Tanzania Lilongwe, Malawi Gaborone, Botswana Mbabane, Swaziland The effectiveness of antiretroviral therapy (ART) Maseru,Lesotho in children in resource-limited settings has not yet been well documented, partly because the proportion of individuals initiated on ART who are children remains low (e.g 7.4% in Lesotho, whereas 15% of all infected individuals in that country are children). Efforts by the Baylor International Pediatric AIDS Initiative (BIPAI) through its Network of Children’s Centres of Excellence (COE) have accelerated scale up of pediatric ART in Africa, now allowing evaluation of effectiveness. The objective of the study was to evaluate the mortality rate on HAART and the effectiveness of HAART among children treated at the COEs in southern Africa. Currently over 68,000 patients are receiving care and treatment within the BIPAI network in Africa and Romania. Hypothesis HAART as administered to children with HIV/AIDS at the BIPAI COE’s in Africa will result in comparable rates of true mortality to those observed in the United States. Primary objective The primary objective is to determine the rate of mortality on HAART over a twelve month period in children, aged 0 to 12 years, enrolled onto therapy at the COE’s. Secondary objectives a) to determine clinical outcomes of children enrolled at the three COEs, in terms of efficacy of HAART, adherence to ARV medication, level of appropriate prescription of cotrimoxazole and correction or improvement of malnutrition. b) to determine the possible relationships between a range of baseline factors and mortality. Methods This retrospective study utilized existing programmatic data from the Lesotho, Malawi, and Swaziland COEs. ART-naïve HIV-infected children < 12 years of age initiating ART and being followed for 12 months were included. Annualized mortality was calculated at three month intervals between February 2008 and September 2009. In addition, mortality rates were estimated overall and for each demographic and clinical subgroup per 100 person-years under a Poisson distribution. Efficacy of ART was defined as improvement in CD4 count of >5% from baseline for children < 5 years or increase of >50 CD4+ cells/ml for children >5-12 years during the first year on ART, with all deaths, discontinuations and lost to follow ups being counted failures. Hazard ratios (HRs) and 95% confidence intervals were estimated for the univariate associations between overall mortality and each demographic and clinical subgroup. The univariate and multivariate analyses were repeated to determine the demographic and clinical factors associated with outcomes with 12 months of HAART. Results Median age at enrollment Median duration on HAART Annualized mortality (Feb. 2008) Annualized mortality (Sep. 2009) Overall mortality Efficacy of HAART Lost-to-follow-up Adherence to HAART (Malawi and Swaziland) % appropriate cotrimoxazole coverage % improvement in malnutrition since enrollment 2.0 years (range 6 days to 11 years) 2.0 years (range 2 days to 6.4 years) 9.3% (101/1082) 4.4% (102/2306) 1.98 deaths/100 person years 71.3% (1450/2035) 9.0% (208/2306) 77.0% had ≥ 95% adherence (962/1250) 88.6% (1159/1308) 87.4% (553/633) Table 1: Top-line results Figure 1. Kaplan-Meier curve for age at study entry The overall mortality rate was 1.98 deaths /100 person-years (95%CI 1.62-2.39). This is comparable to overall mortality rates for HIV infected children reported for the United States. 3 The US Pediatric AIDS Clinical Trials Group 219/291C reported an overall mortality rate of 1.47 deaths/100 3 person-years (95%CI 1.31-1.65) for children enrolled and followed up between April 1993 and December 2006 . However, they reported a declining mortality rate over the study years with mortality rates between 0.5-0.8 deaths/100 person-years between 2000 and 2006 in the post-HAART era. In addition, comparisons between the mortality rates between the PACTG and BIPAI cohorts should be made with caution because of the different age distributions between the cohorts. Mortality was highest in the first year of HAART treatment, 78% of all deaths occurring within that period. With regard to baseline factors, age less than one year, WHO stage IV and evidence of malnutrition at enrolment were associated with higher mortality, while primary caregiver other than the mother or father was associated with lower mortality (figure 1 and table 2). Country and gender were unrelated to mortality. Baseline factor Age at entry < 1 year 1 - 2.9 years 3 - 6.9 years 7 - 12 years WHO stage at entry I II III IV missing Primary caregiver Mother/father Other relative Non relative Missing Nutritional status Normal Mild malnutrition Moderate malnutrition Severe malnutrition Missing Conclusions Authors: R.S. Wanless 1 , M. Kabue 2 , P. Kazembe 2 , E. Mohapi 3 , L. Thah- ane 3 , A. Devlin 3 , N.S. Hailu 4 , D. McCollum 4 , N. Calles 5 , G. Schutze 5 , M. Kline 5 , M. 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