This application requests continuation of a Multi-center AIDS Cohort Study (MACS) Pathogenesis Research Laboratory (MPRL) which consists of a consortium of investigators at John Hopkins University, the University of Pittsburgh, and the University of Washington. The scientific agenda for this application is based on the accomplishments of the current funding period, especially the finding of an ordered cascade of events which characterized the 3-4 years before the onset of clinically defined AIDS in those HIV-1 infected MACS participants who progressed to advanced HIV-1 disease. The hallmarks of this cascade included increases in viral intra-timepoint diversity and divergence from the founder strain, which then stabilized or declined; detection of X4 (CXCR4-utilizing) strains of HIV-1 in the peripheral blood, at least transiently; and loss of normal of circulating total T (CD3+) lymphocytes (failure of T cell homeostasis), including preferential loss of naive CD4+ T cells.
The specific aims of the present application, therefore, are: 1) To confirm this cascade and the stages of asymptomatic HIV-1 infection it defines; 2) To determine the specific mutations and patterns of evolution required for outgrowth of X4 viruses; 3) To elucidate the role of CD8+ T cells in controlling HIV replication and evolution; and 4) To use the above information to determine the impact of virologic and immunologic status at the initiation of highly active anti-retroviral therapy (HAART) on the response to HAART. Both retrospective and real-time study designs will be used, to take advantage of the excellent MACS cohort follow-up as well as repository of lymphocyte, plasma, and clinical data. Results from these studies should help to improve understanding of a) mechanisms influencing the rate of HIV-1 disease progression and b) optimal ways to balance the benefits and risks of HAART.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01AI037984-06
Application #
6373474
Study Section
Special Emphasis Panel (ZAI1-ACS-A (J1))
Program Officer
Williams, Carolyn F
Project Start
2000-04-01
Project End
2004-03-31
Budget Start
2001-04-01
Budget End
2002-03-31
Support Year
6
Fiscal Year
2001
Total Cost
$755,381
Indirect Cost
Name
Johns Hopkins University
Department
Microbiology/Immun/Virology
Type
Schools of Public Health
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Elion, Richard A; Althoff, Keri N; Zhang, Jinbing et al. (2018) Recent Abacavir Use Increases Risk of Type 1 and Type 2 Myocardial Infarctions Among Adults With HIV. J Acquir Immune Defic Syndr 78:62-72
Grover, Surbhi; Desir, Fidel; Jing, Yuezhou et al. (2018) Reduced Cancer Survival Among Adults With HIV and AIDS-Defining Illnesses Despite No Difference in Cancer Stage at Diagnosis. J Acquir Immune Defic Syndr 79:421-429
Yanik, Elizabeth L; Hernández-Ramírez, Raúl U; Qin, Li et al. (2018) Brief Report: Cutaneous Melanoma Risk Among People With HIV in the United States and Canada. J Acquir Immune Defic Syndr 78:499-504
Altekruse, Sean F; Shiels, Meredith S; Modur, Sharada P et al. (2018) Cancer burden attributable to cigarette smoking among HIV-infected people in North America. AIDS 32:513-521
Tipton, Laura; Cuenco, Karen T; Huang, Laurence et al. (2018) Measuring associations between the microbiota and repeated measures of continuous clinical variables using a lasso-penalized generalized linear mixed model. BioData Min 11:12
AIDS-defining Cancer Project Working Group of IeDEA, COHERE in EuroCoord (2018) Non-Hodgkin lymphoma risk in adults living with HIV across five continents. AIDS 32:2777-2786
Anderegg, Nanina; Johnson, Leigh F; Zaniewski, Elizabeth et al. (2017) All-cause mortality in HIV-positive adults starting combination antiretroviral therapy: correcting for loss to follow-up. AIDS 31 Suppl 1:S31-S40
Drozd, Daniel R; Kitahata, Mari M; Althoff, Keri N et al. (2017) Increased Risk of Myocardial Infarction in HIV-Infected Individuals in North America Compared With the General Population. J Acquir Immune Defic Syndr 75:568-576
Dubrow, Robert; Qin, Li; Lin, Haiqun et al. (2017) Association of CD4+ T-cell Count, HIV-1 RNA Viral Load, and Antiretroviral Therapy With Kaposi Sarcoma Risk Among HIV-infected Persons in the United States and Canada. J Acquir Immune Defic Syndr 75:382-390
Jiamsakul, Awachana; Kariminia, Azar; Althoff, Keri N et al. (2017) HIV Viral Load Suppression in Adults and Children Receiving Antiretroviral Therapy-Results From the IeDEA Collaboration. J Acquir Immune Defic Syndr 76:319-329

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