We propose to form an HIV-I Acute Infection and Early Disease Research Unit that will use innovative approaches to recruit and retain at least 25 persons with acute HIV and 40 with early HIV infection each year for 4 years. These subjects will constitute a cohort for longitudinal assessment of Clinical, immunologic and virologic endpoints of HIV infection. Consenting cohort members will be randomized to receive combination antiviral treatment (zidovudine, lamavudine and nelfinavir) with or without IL-2. We will assess whether IL-2 enhances the ability of combination therapy to improve immunologic measures and maintain suppression of virus below detectable levels. Those declining randomization will be followed and assessed as observational controls. The specifiC objectives in the investigation of early HIV pathogenesis will be to study treated and untreated persons to: Evaluate whether viral load in blood, PBMCs, tonsil, and other sites influences pathogenesis and assess whether kinetics of viremia can be used to estimate time from infection; Determine the pattern of immunologic activation as measured by cell surface markers, levels of apoptosis, soluble and cell-associated cytokines, and reactivation of herpes viruses; Examine whether the extent of CD8+ cell antiviral activity as measured by non-cytotoxic and cytotoxic responses affects the kinetics of viral replication and viral load; Determine whether a broad cellular immune response to HIV infection, measured by T cell repertoire, correlates with the patterns of cellular immune antiviral responses. These virologic and immunologic studies will provide insights into the pathogenesis of HIV infection and contribute to the development new approaches for its treatment.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01AI041531-02
Application #
2673033
Study Section
Special Emphasis Panel (ZAI1-SCO-A (M1))
Project Start
1997-07-01
Project End
2001-06-30
Budget Start
1998-07-01
Budget End
1999-06-30
Support Year
2
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Moore, Camille M; MaWhinney, Samantha; Forster, Jeri E et al. (2017) Accounting for dropout reason in longitudinal studies with nonignorable dropout. Stat Methods Med Res 26:1854-1866
Jain, Vivek; Hartogensis, Wendy; Bacchetti, Peter et al. (2013) Antiretroviral therapy initiated within 6 months of HIV infection is associated with lower T-cell activation and smaller HIV reservoir size. J Infect Dis 208:1202-11
Hecht, Frederick M; Wellman, Robert; Busch, Michael P et al. (2011) Identifying the early post-HIV antibody seroconversion period. J Infect Dis 204:526-33
Meditz, Amie L; MaWhinney, Samantha; Allshouse, Amanda et al. (2011) Sex, race, and geographic region influence clinical outcomes following primary HIV-1 infection. J Infect Dis 203:442-51
Willberg, Christian B; Garrison, Keith E; Jones, R Brad et al. (2010) Rapid progressing allele HLA-B35 Px restricted anti-HIV-1 CD8+ T cells recognize vestigial CTL epitopes. PLoS One 5:e10249
Hecht, Frederick M; Hartogensis, Wendy; Bragg, Larry et al. (2010) HIV RNA level in early infection is predicted by viral load in the transmission source. AIDS 24:941-5
Ndhlovu, Lishomwa C; Sinclair, Elizabeth; Epling, Lorrie et al. (2010) IL-2 immunotherapy to recently HIV-1 infected adults maintains the numbers of IL-17 expressing CD4+ T (T(H)17) cells in the periphery. J Clin Immunol 30:681-92
Naeger, David M; Martin, Jeffrey N; Sinclair, Elizabeth et al. (2010) Cytomegalovirus-specific T cells persist at very high levels during long-term antiretroviral treatment of HIV disease. PLoS One 5:e8886
Markowitz, Martin; Vaida, Florin; Hare, C Bradley et al. (2010) The virologic and immunologic effects of cyclosporine as an adjunct to antiretroviral therapy in patients treated during acute and early HIV-1 infection. J Infect Dis 201:1298-302
Apuzzo, Linda G; Vaida, Florin; Gallant, Joel E et al. (2009) Tolerability and efficacy of PI versus NNRTI-based regimens in subjects receiving HAART during acute or early HIV infection. J Acquir Immune Defic Syndr 50:267-75

Showing the most recent 10 out of 57 publications