AEGiS-05CROI: Immunological reconstitution after triple combination therapy in HIV-1 infection: a composite of redistribution and proliferation.

5th Conference on Retroviruses and Opportunistic Infections

Chicago, IL - February 1-5, 1998

Immunological reconstitution after triple combination therapy in HIV-1 infection: a composite of redistribution and proliferation.

Conf Retroviruses Opportunistic Infect 1998 Feb 1-5; 5th:82 (abstract no. 20)

Miedema F, Pakker NG, Notermans DW, De Boer R, Kostense S, Roos MT, De Wolf F, Hill A, Leonard JM, Danner SA, Raaphorst FM, Schellekens PT; Academic Medical Centre, University of Amsterdam, The Netherlands.

To study the origin of CD4+ T cells repopulating the blood following anti-retroviral therapy, we investigated the kinetics of naïve and memory T cell repopulation. In addition, functional properties of peripheral blood T cells were evaluated. Patients (n=33) were treated with AZT, 3TC and ritonavir directly from the onset of the study or started with monotherapy ritonavir, and AZT and 3TC were added 3 weeks later. In 90% of the patients on treatment RNA load levels became undetectable. CD4+ but also CD8+ T cell numbers increased significantly in the first 3 weeks, accompanied by functional improvement in vitro. Repopulation of memory CD4+ and CD8+ T cells showed a biphasic pattern with an immediate strong increase in the first 3 weeks (10(6) cells/day) without a further rise later on. Numbers of CD45RA + CD62L+ naïve CD4+ and CD8+ T cells increased continuously, but slowly, at a rate of 5.7x10(6) cells per day. Mathematical modelling showed that the rapid memory T cell increase can either be explained by proliferation or by redistribution. Redistribution can explain the striking correlation between the initial rise of memory CD4+ and CD8+ T cells, which correlated with baseline CD4+ T cells counts and viral load. These results and preliminary results of TCR CDR3 spectrotype analyses of memory and naïve CD4+ T cells, indicate that triple combination therapy initially causes a quick redistribution of oligoclonal memory T cells to the blood followed by a slow repopulation with presumably de novo produced naïve T cells rebuilding the full TCR repertoire. These studies suggest that restoration of the immune system following HAART may be slower than anticipated, comparable with recovery after bone marrow transplantation.

Keywords: AEGIS, HIV Infections, Viral Load, Anti-HIV Agents, Zidovudine, CD4 Lymphocyte Count, Antiretroviral Therapy, Highly Active, Lamivudine, T-Lymphocytes, HIV Protease Inhibitors, Antigens, CD4, Antigens, CD45, Reverse Transcriptase Inhibitors, Antigens, CD8, In Vitro, Human, immunology, AIDS

1998-02-01
20

Copyright © 1998 - Foundation for Retrovirology and Human Health (IAS). Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed from National Library of Medicine.