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Mortality of HIV-infected and uninfected children in a longitudinal clinical cohort in rural southwest Uganda during 8 years of follow-up, 2002-2009. Munyagwa M, 1 Baisley K, 2 Levin J, 1 Atuhumuza E, 1 Nalaaki M, 1 Nakibuuka G, 1 Nalugya M, 1 Grosskurth H, 1,2 Maher D 1,2
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Mortality of HIV-infected and uninfected children in a longitudinal clinical cohort in rural southwest Uganda during 8 years of follow-up, 2002-2009 Munyagwa M,1Baisley K,2 Levin J,1 Atuhumuza E,1 Nalaaki M,1 Nakibuuka G,1 Nalugya M,1 Grosskurth H,1,2 Maher D 1,2 1 MRC/UVRI Uganda Research Unit on AIDS 2London School of Hygiene and Tropical Medicine
Background • HIV infection is a leading cause of death among children in developing countries • Care of HIV-infected children poses a great challenge • Early initiation of ART has been found effective in reducing mortality • Impact of early ART initiation in rural Africa requires measurement of baseline mortality
Objectives • To determine the impact of HIV infection on child mortality • To identify risk factors for mortality among HIV-infected children
The study setting Masaka District, southwest Uganda 4
Methods • Participants in 3 categories: HIV-infected, HIV-exposed and uninfected, and HIV-unexposed children aged 6 m to 15 y • Enrolled in a longitudinal clinical cohort from a larger population cohort, July 02 – Aug 09 • Cotrimoxazole prophylaxis since 2002 • ART since 2005 • Clinical and lab data were collected on routine follow-up every 3 months
Methods • Person years (pyrs) at risk were calculated from time of enrolment until earliest date of ART initiation, death or last clinic visit • Cox proportional hazards regression was used to estimate hazard ratios (HR) for mortality
Outcomes by HIV status *Includes 41 children eligible for ART **Includes 31 children initiating ART
Mortality rates by HIV status *Includes 38 person-years in 41 children who were eligible for ART but not on it
Risk factors for mortality among HIV-infected children not on ART *Adjusted HR represents increase in risk of mortality for a one unit decrease in CD4 category.
Risk factors for mortality among all HIV-infected children *Adjusted HR represents increase in risk of mortality for a one unit decrease in CD4 category.
Discussion (1) • Findings • confirm much higher mortality among HIV-infected children not on ART than among HIV-uninfected children • provide baseline to monitor impact of early ART initiation on mortality • Among HIV-infected children not on ART, mortality was highest in those less than 2 years old as found elsewhere, due to more rapid disease progression. • Mortality among HIV-infected children not on ART may be higher outside research settings.
Discussion (2) • Chronic malnutrition and severe anaemia are associated with disease progression, thus increasing risk of mortality. • The lack of an association between ART and decreased mortality may be because of delays in starting ART and the small numbers treated so far.
Recommendations • Monitoring mortality is important to determine success of ART. • Decreased mortality requires intensive efforts to prevent mother to child transmission of HIV and to promote early infant HIV diagnosis and treatment. • In addition to ART, management of HIV-infected children should include nutritional support and prevention and management of anemia.
Acknowledgements Study participants and guardians Staff Collaborating departments MRC (UK) for funding