on page 2 of the application) In an effort to determine how long present treatments must be continued to permit elimination of the long-lived viral DNA reservoir (if possible) and to provide a basis for the development of new therapeutic strategies, the nature of this reservoir must be characterized. This project will study the decay rate of this reservoir and the applicability of existing paradigms of pre- and post-integration viral latency through three aims: (1) Infectivity assays and serial quantitative assays for both integrated and unintegrated HIV DNA will be used to determine whether infectivity associated with latently infected cells in the setting of undetectable (<50 copies/ml) plasma viremia reflects pre- or post-integration latency and whether the exhaustion of this reservoir is feasible with current therapies. (2) HIV pol sequences of sequential HIV isolates from treatment suppressed patients, will be studied to monitor for the development of drug resistance and sequence evolution which would indicate that this population of cells is being replenished by ongoing viral replication and thus be associated with a risk for treatment failure. (3) The application of sensitive quantitative assays for spliced HIV transcripts will be used to determine whether, some or all latently infected cells remain transcriptionally active thereby producing one or more gene products that can be targeted by the host immune response.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI043752-03
Application #
6373949
Study Section
AIDS and Related Research Study Section 3 (ARRC)
Program Officer
Cairns, Scott
Project Start
1999-04-01
Project End
2003-03-31
Budget Start
2001-04-01
Budget End
2002-03-31
Support Year
3
Fiscal Year
2001
Total Cost
$204,331
Indirect Cost
Name
Veterans Medical Research Fdn/San Diego
Department
Type
DUNS #
933863508
City
San Diego
State
CA
Country
United States
Zip Code
92161
Beliakova-Bethell, Nadejda; Hezareh, Marjan; Wong, Joseph K et al. (2017) Relative efficacy of T cell stimuli as inducers of productive HIV-1 replication in latently infected CD4 lymphocytes from patients on suppressive cART. Virology 508:127-133
Osorio, Georgina; Hoenigl, Martin; Quartarolo, Jennifer et al. (2017) Evaluation of opt-out inpatient HIV screening at an urban teaching hospital. AIDS Care 29:1014-1018
Hightower, George K; Wong, Joseph K; Letendre, Scott L et al. (2012) Higher HIV-1 genetic diversity is associated with AIDS and neuropsychological impairment. Virology 433:498-505
Mehta, Sanjay R; Kosakovsky Pond, Sergei L; Young, Jason A et al. (2012) Associations between phylogenetic clustering and HLA profile among HIV-infected individuals in San Diego, California. J Infect Dis 205:1529-33
Pacold, Mary E; Pond, Sergei L Kosakovsky; Wagner, Gabriel A et al. (2012) Clinical, virologic, and immunologic correlates of HIV-1 intraclade B dual infection among men who have sex with men. AIDS 26:157-65
Mehta, Sanjay R; Nguyen, Vu T; Osorio, Georgina et al. (2011) Evaluation of pooled rapid HIV antibody screening of patients admitted to a San Diego Hospital. J Virol Methods 174:94-8
Morris, Sheldon R; Little, Susan J; Cunningham, Terry et al. (2010) Evaluation of an HIV nucleic acid testing program with automated Internet and voicemail systems to deliver results. Ann Intern Med 152:778-85
Butler, David M; Delport, Wayne; Kosakovsky Pond, Sergei L et al. (2010) The origins of sexually transmitted HIV among men who have sex with men. Sci Transl Med 2:18re1
Smith, Davey M; May, Susanne J; Tweeten, Samantha et al. (2009) A public health model for the molecular surveillance of HIV transmission in San Diego, California. AIDS 23:225-32
Smith, Davey M; May, Susanne J; Pérez-Santiago, Josué et al. (2009) The use of pooled viral load testing to identify antiretroviral treatment failure. AIDS 23:2151-8

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