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.

Original publication

DOI

10.1073/pnas.96.26.15167

Type

Journal article

Journal

Proceedings of the National Academy of Sciences of the United States of America

Publication Date

12/1999

Volume

96

Pages

15167 - 15172

Addresses

Wellcome Trust Centre for the Epidemiology of Infectious Disease, University of Oxford OX1 3PS, United Kingdom. neil.ferguson@zoo.ox.ac.uk

Keywords

Lymph Nodes, CD4-Positive T-Lymphocytes, Humans, HIV-1, HIV Infections, RNA, Viral, Zidovudine, Tetanus Toxoid, Anti-HIV Agents, CD4 Lymphocyte Count, Drug Resistance, Microbial, Models, Theoretical, Drug Therapy, Combination, Reverse Transcriptase Inhibitors, HIV Protease Inhibitors