Increasing numbers of HIV infected children in Sub-Saharan Africa now benefit from treatment with antiretroviral therapy but current WHO and national guidelines for antiretroviral (ARV) initiation stress impairment of immune function (CD4% and the occurrence of opportunistic infections) as indications for starting treatment. There are conflicting data on the magnitude of the neuro-developmental delay due to HIV in sub- Saharan Africa. Uncertainty exists on how the high frequency of co-morbidities and how different HIV subtypes prevalent in sub-Saharan Africa might impact disease course. Of note co-morbidities such as malaria are well known to impact child development and unless accounted for, may distort associations between HIV and neurocognitive impairment. For HIV infected children deferring therapy because of high CD4%, it is not known what might predict significant neuro-developmental complications or whether, once manifest, whether such impairment is fully reversible with ARV therapy. The current application utilizes existing pediatric cohorts and infrastructure at the Makerere University/UCSF Joint Malaria Study project in Kampala, Uganda and neuro- medical, behavioral and laboratory expertise in Uganda and in the U.S. to study the neuro-developmental consequences of deferred ARV therapy in the background of co- incident malaria. We will assess HIV subtype composition at the viral gene specific level and HIV DNA viral load, (both determined from dried blood spots (dbs)) and estimates of past malaria exposure as novel predictors of HIV related neuro-developmental delay. Additionally, this will be, to our knowledge, the first attempt to analyze and contrast HIV and malaria related neurocognitive dysfunction using uniform tools under one study. When these studies are complete we will have an improved understanding of the determinants of HIV neurocognitive impairment in both treatment na?ve and on treatment patients. Furthermore, we will have the necessary preliminary data and tools to pursue definitive, prospective studies that include information on malaria co-infection, viral subtype and other biomarkers in planning interventional studies that address neuro- developmental delay in HIV infected African children. These studies are relevant because they have the potential to alter pediatric HIV treatment paradigms in the developing world and to ameliorate the burden of individual and societal neuro- developmental disability. HIV infection can affect the brain function of adults and children. In this study, we will try to determine how much HIV in Uganda can alter the brain development in children what can be used to predict which child will have this complication and whether anti-HIV treatment prevents this.
