HIV associated neurocognitive disorder (HAND) is a common neurological complication of HIV in the US, and our preliminary data suggest that 31% of HIV+ individuals in Uganda may have HIV dementia, the most severe stage of HAND. HIV- associated psychiatric morbidity is also common. There is also evidence that HIV subtype D is associated with more prevalent neurocognitive morbidity than subtype A in individuals with advanced immunosuppression. However, there are no large population based studies of the neurocognitive or psychiatric status of HIV+ African individuals. The Rakai Health Sciences Program (RHSP), Uganda, offers a unique opportunity to conduct such research. The RHSP can identify HIV+ individuals with moderate (CD4 350-500) and more severe (CD4 ?200) immunosuppression from its population based cohort and HIV clinic services. Rakai District is also one of the few regions where a heterosexual epidemic involves different HIV subtypes (A, D, recombinants), enabling us to compare subtype effects on co-morbidities.
Specific aims are: 1. At baseline, to assess whether ART nave HIV+ adults aged ? 20 years with moderate immunosuppression (CD4 350-500), and advanced immunosuppression (CD4 ? 200) experience key neurocognitive/psychiatric co-morbidities, and reduced functional status, compared to age and gender matched HIV- adults in the same Rakai population (the latter will provide normative data as yet unavailable in rural Uganda), 2. To assess the trajectory of these co-morbidities in the HIV+s at two years of follow-up by HIV subtype and level of immunosuppression prior to and after ART initiation, and 3. To define the level of compartmentalized virus in the CSF of individuals with and without dementia stratified by HIV subtype. Hypotheses: 1. ART nave HIV+ individuals with moderate and advanced immunosuppression have higher prevalence and severity of neurocognitive/psychiatric morbidity, and functional disability, compared to HIV- persons in the same communities, 2. ART will reduce the prevalence and severity of co-morbidities, but rates will remain significantly higher than in HIV- persons, 3. Neurological co-morbidities in HIV+ persons, whether or not they are on ART, adversely affect functional status, increasing health and social support needs, 4. HIV subtype D is associated with an accelerated risk of dementia than subtype A among individuals with advanced immunosuppression, 5. Greater viral genetic compartmentalization in the CSF correlates with dementia and is increased with subtype D compared to A. The study will provide epidemiological and clinical data for the development of prevention and support programs related to neurocognitive /psychiatric co-morbidities, and mechanistic data on HIV-related CNS pathology.

Public Health Relevance

This study will be the first large population-based study to systematically address questions regarding neurocognitive and associated depressive symptoms and functional status in HIV+ African individuals, compared to HIV-negative persons from the same communities. Such data are urgently needed to: 1) determine the rates of preventable HIV co-morbidities in order to develop appropriate interventions; 2) better plan ART-related health services and social support; 3) and to provide insights into co-morbidities due to HIV effects prior to ART initiation, which could have implications for pre-ART care. The study will also provide important data to examine the role of viral compartmentalization in the underlying pathogenesis of HAND in Africa.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
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Special Emphasis Panel (ZRG1-AARR-F (55)R)
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Joseph, Jeymohan
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Johns Hopkins University
Public Health & Prev Medicine
Schools of Public Health
United States
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Sacktor, Ned (2018) Changing clinical phenotypes of HIV-associated neurocognitive disorders. J Neurovirol 24:141-145
Abassi, Mahsa; Morawski, Bozena M; Nakigozi, Gertrude et al. (2017) Cerebrospinal fluid biomarkers and HIV-associated neurocognitive disorders in HIV-infected individuals in Rakai, Uganda. J Neurovirol 23:369-375
Obermeit, Lisa C; Beltran, Jessica; Casaletto, Kaitlin B et al. (2017) Evaluating the accuracy of self-report for the diagnosis of HIV-associated neurocognitive disorder (HAND): defining ""symptomatic"" versus ""asymptomatic"" HAND. J Neurovirol 23:67-78
Saylor, Deanna; Dickens, Alex M; Sacktor, Ned et al. (2016) HIV-associated neurocognitive disorder--pathogenesis and prospects for treatment. Nat Rev Neurol 12:234-48
Sacktor, Ned; Nakasujja, Noeline; Redd, Andrew D et al. (2014) HIV subtype is not associated with dementia among individuals with moderate and advanced immunosuppression in Kampala, Uganda. Metab Brain Dis 29:261-8
Sacktor, Ned; Robertson, Kevin (2014) Evolving clinical phenotypes in HIV-associated neurocognitive disorders. Curr Opin HIV AIDS 9:517-20