Kaufmann G, Zaunders J, Murray J, Kelleher AD, Lewin SR, Solomon A, Smith D, Cooper DA; Conference on Retroviruses and Opportunistic Infections.

Program Abstr 8th Conf Retrovir Oppor Infect Conf Retrovir Oppor Infect 8th 2001 Chic Ill. 2001 Feb 4-8; 8: 157 (abstract no. 382).

NCHECR, Sydney, Australia.

Background: A major goal of antiretroviral HIV-1 therapy is the reversal of HIV-1-associated immunological dysfunction. However, the pathogenetic mechanisms involved and their significance are largely unknown. Methods: Based on the life cycle of naive, activated and memory CD4+ T cell subsets, a mathematical model of immune reconstitution was developed and applied to data for T cell subsets in individuals with acute (n = 28) or chronic (n = 30) HIV-1 infection receiving potent antiretroviral therapy. The final model considered three pathways of immune reconstitution for naive cells, including thymic production, peripheral expansion and re-distribution of naive cells from lymphoid tissue. The reconstitution of the memory compartment was fitted through antigen- dependent activation, differentiation and expansion of naive cells and peripheral expansion of memory cells as well as re-distribution of memory cells, trapped in the lymphoid tissue. Results: Estimated median half-lives for naive and memory CD4+ T cells were 114 and 21 days, while total production rates were 9.1 x 10(7) and 2.4 x 10(9) cells/day, respectively. Peripheral expansion and thymic production contributed equally to the regeneration of naive cells, but peripheral expansion of memory cells was larger than production of these cells by differentiation of naive cells. A comparison of subjects with acute and chronic HIV-1 infection revealed that the main difference was the more rapid release of a larger number of naive cells in treated acute HIV-1 infection. Thymic function and peripheral expansion rates of naive cells as well as the parameters for memory cells, however, were similar in both cohorts. Conclusions: In conclusion, a model of immune reconstitution was developed that fitted well the time course of CD4+ T cell subsets and provided realistic estimates for the turnover of these cells. The model appears to be a useful tool to compare immune reconstitution in different cohorts of HIV-1-infected individuals.

Publication Types:

• Meeting Abstracts

Keywords:

• Antiretroviral Therapy, Highly Active
• HIV Infections
• HIV-1
• Models, Immunological
• Models, Theoretical
• T-Lymphocyte Subsets
• T-Lymphocytes
• Thymus Gland
• metabolism

Other ID:

• GWAIDS0006669

UI: 102244165

From Meeting Abstracts