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

Neil M. Ferguson*, Frank Dewolf, Azra C. Ghani, Christophe Fraser, Christl A. Donnelly, Peter Reiss, Joep M.A. Lange, Sven A. Danner, Geoff P. Garnett, Jaap Goudsmit, Roy M. Anderson

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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 vital 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 languageEnglish
Pages (from-to)15167-15172
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume96
Issue number26
DOIs
Publication statusPublished - 21 Dec 1999

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