Antigen-driven CD4+ T cell and HIV-1 dynamics: Residual viral replication under highly active antiretroviral therapy

Antigen-driven CD4+ T cell and HIV-1 dynamics: Residual viral replication under highly active antiretroviral therapy

^*Wellcome Trust Centre for the Epidemiology of Infectious Disease, University of Oxford OX1 3PS, United Kingdom; and ^§Academic Medical Centre, Departments of ^¶Human Retrovirology and ^**Internal Medicine, and ^‖Division of Infectious Diseases, Tropical Medicine, and AIDS, University of Amsterdam, Meiberg Dreef, 151105 AZ Amsterdam, The Netherlands

Communicated by David Cox, Nuffield College, University of Oxford, Oxford, United Kingdom (received for review July 3, 1999)

Abstract

Antigen-induced stimulation of the immune system can generate heterogeneity in CD4+ T cell division rates capable of explaining the temporal patterns seen in the decay of HIV-1 plasma RNA levels during highly active antiretroviral therapy. Posttreatment increases in peripheral CD4+ T cell counts are consistent with a mathematical model in which host cell redistribution between lymph nodes and peripheral blood is a function of viral burden. Model fits to patient data suggest that, although therapy reduces HIV replication below replacement levels, substantial residual replication continues. This residual replication has important consequences for long-term therapy and the evolution of drug resistance and represents a challenge for future treatment strategies.

Footnotes

↵ † N.M.F. and F.d.W. contributed equally to this work.
↵ ‡ To whom reprint requests should be addressed. E-mail: neil.ferguson{at}zoo.ox.ac.uk.
Abbreviations:

HAART,

highly active antiretroviral therapy;

RTI,

reverse transcriptase inhibitor;

AZT,

3′-azido-3′-deoxythymidine