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. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21MH083573-01
Application #
7494765
Study Section
Special Emphasis Panel (ZMH1-ERB-S (02))
Program Officer
Brouwers, Pim
Project Start
2008-03-25
Project End
2010-02-28
Budget Start
2008-03-25
Budget End
2009-02-28
Support Year
1
Fiscal Year
2008
Total Cost
$233,427
Indirect Cost
Name
Northern California Institute Research & Education
Department
Type
DUNS #
613338789
City
San Francisco
State
CA
Country
United States
Zip Code
94121
Joseph, Jeymohan; Achim, Cristian L; Boivin, Michael J et al. (2013) Global NeuroAIDS roundtable. J Neurovirol 19:1-9
Pillai, Satish K; Abdel-Mohsen, Mohamed; Guatelli, John et al. (2012) Role of retroviral restriction factors in the interferon-?-mediated suppression of HIV-1 in vivo. Proc Natl Acad Sci U S A 109:3035-40
Ruel, Theodore D; Boivin, Michael J; Boal, Hannah E et al. (2012) Neurocognitive and motor deficits in HIV-infected Ugandan children with high CD4 cell counts. Clin Infect Dis 54:1001-9
Yukl, Steven A; Li, Peilin; Fujimoto, Katsuya et al. (2011) Modification of the Abbott RealTime assay for detection of HIV-1 plasma RNA viral loads less than one copy per milliliter. J Virol Methods 175:261-5
Li, Peilin; Ruel, Theodore; Fujimoto, Katsuya et al. (2010) Novel application of Locked Nucleic Acid chemistry for a Taqman assay for measuring diverse human immunodeficiency virus type 1 subtypes. J Virol Methods 170:115-20
Boivin, Michael J; Ruel, Theodore D; Boal, Hannah E et al. (2010) HIV-subtype A is associated with poorer neuropsychological performance compared with subtype D in antiretroviral therapy-naive Ugandan children. AIDS 24:1163-70
Heaton, R K; Clifford, D B; Franklin Jr, D R et al. (2010) HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy: CHARTER Study. Neurology 75:2087-96
Ruel, Theodore; Ssewanyana, Isaac; Achan, Jane et al. (2009) Dynamics of T cell activation accompanying CD4 recovery in antiretroviral treated HIV-infected Ugandan children. Clin Immunol 131:410-4