We are proposing a collaborative, comprehensive, multidisciplinary, multicenter integrated programme of innovative and relevant research on AIDS in South Africa to address the appropriate treatment for adults and children in a family model, TB prevention, and the development of less costly diagnostic and monitoring laboratory tests. The primary aim of this program is to contribute knowledge that will assist in safeguarding the household from the effects of the HIV/AIDS epidemic. We propose to do this with five projects and three cores that are linked via tight communication including email, conference calls and face-to-face meetings. All address the problem of """"""""Safeguard the Household by"""""""": ? Identifying HIV+ positive people in Cape Town and Soweto ? Identifying those family members who are positive ? Testing simple treatment regimens for those age one year to adult which can be administered in primary care settings, where often there are no physicians (Project 1) ? Testing whether early treatment in infancy and treatment interruption influence the outcome of disease in children (Project 2) ? Studying the impact of HAART on HIV morbidity and mortality in a well circumscribed and well described township in Cape Town where many of our families are located (Project 3) ? Testing the efficacy of a new pneumococcal conjugate vaccine and hemophilus vaccination in infants of the same cohort (Project 4) * To obtain cells and plasma on all of our families at baseline for further analyses of HIV Clade C characteristics, host genetics and host immune response and their impact on disease progression and response to therapy (Study 1 of Project 5) ? Developing and validating better, cheaper ways to diagnose and monitor HIV infection, and to store and transport blood samples (Study 2 and 3 of Project 5) The projects are supported by three cores, which serve all the projects in order to provide: ? Effective administrative and research support, including data management and statistics, regulatory affairs and centralized pharmacy functions (Core A) ? Efficient and accurate laboratory services from a laboratory group with extensive experience in research work and a well developed and certified laboratory system (Core B) ? A unique program of training and capacity development that recognizes the effects of apartheid on South Africa's research establishment and will strive to create expertise and ability, particularly in previously disadvantaged groups, that will help sustain an effective research infrastructure into the future. In addition this program will provide for dissemination of research findings to policy makers and key role-players, to help ensure the rapid translation of research into action (Core C)

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI053217-08
Application #
7921589
Study Section
Special Emphasis Panel (NSS)
Project Start
Project End
Budget Start
2009-09-01
Budget End
2010-08-31
Support Year
8
Fiscal Year
2009
Total Cost
$919,750
Indirect Cost
Name
Wits Health Consortium (Pty), Ltd
Department
Type
DUNS #
639391218
City
Johannesburg
State
Country
South Africa
Zip Code
Nwosu, Emmanuel C; Robertson, Frances C; Holmes, Martha J et al. (2018) Altered brain morphometry in 7-year old HIV-infected children on early ART. Metab Brain Dis 33:523-535
Toich, Jadrana T F; Taylor, Paul A; Holmes, Martha J et al. (2017) Functional Connectivity Alterations between Networks and Associations with Infant Immune Health within Networks in HIV Infected Children on Early Treatment: A Study at 7 Years. Front Hum Neurosci 11:635
Jankiewicz, Marcin; Holmes, Martha J; Taylor, Paul A et al. (2017) White Matter Abnormalities in Children with HIV Infection and Exposure. Front Neuroanat 11:88
Lewis, Joanna; Payne, Helen; Walker, A Sarah et al. (2017) Thymic Output and CD4 T-Cell Reconstitution in HIV-Infected Children on Early and Interrupted Antiretroviral Treatment: Evidence from the Children with HIV Early Antiretroviral Therapy Trial. Front Immunol 8:1162
Innes, Steve; van Toorn, Ronald; Otwombe, Kennedy et al. (2017) Late-Onset Hiv Encephalopathy In Children With Long-Standing Virologic Suppression Followed By Slow Spontaneous Recovery Despite no Change In Antiretroviral Therapy: 4 Case Reports. Pediatr Infect Dis J 36:e264-e267
Mbugua, Kenneth K; Holmes, Martha J; Cotton, Mark F et al. (2016) HIV-associated CD4+/CD8+ depletion in infancy is associated with neurometabolic reductions in the basal ganglia at age 5 years despite early antiretroviral therapy. AIDS 30:1353-62
Ackermann, C; Andronikou, S; Saleh, M G et al. (2016) Early Antiretroviral Therapy in HIV-Infected Children Is Associated with Diffuse White Matter Structural Abnormality and Corpus Callosum Sparing. AJNR Am J Neuroradiol 37:2363-2369
van Zyl, Gert U; Bedison, Margaret A; van Rensburg, Anita Janse et al. (2015) Early Antiretroviral Therapy in South African Children Reduces HIV-1-Infected Cells and Cell-Associated HIV-1 RNA in Blood Mononuclear Cells. J Infect Dis 212:39-43
Madhi, Shabir A; Izu, Alane; Nunes, Marta C et al. (2015) Longitudinal study on Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus nasopharyngeal colonization in HIV-infected and -uninfected infants vaccinated with pneumococcal conjugate vaccine. Vaccine 33:2662-9
Alhamud, A; Taylor, Paul A; Laughton, Barbara et al. (2015) Motion artifact reduction in pediatric diffusion tensor imaging using fast prospective correction. J Magn Reson Imaging 41:1353-64

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