Antigen-driven CD4+ T cell and HIV-1 dynamics: residual viral replication under highly active antiretroviral therapy.
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.
Ferguson
N M
NM
Wellcome Trust Centre for the Epidemiology of Infectious Disease, University of Oxford OX1 3PS, United Kingdom. neil.ferguson@zoo.ox.ac.uk
deWolf
F
F
Ghani
A C
AC
Fraser
C
C
Donnelly
C A
CA
Reiss
P
P
Lange
J M
JM
Danner
S A
SA
Garnett
G P
GP
Goudsmit
J
J
Anderson
R M
RM
D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004352:Drug Resistance, Microbial; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008198:Lymph Nodes / Q000821:virology; D008962:Models, Theoretical; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D013745:Tetanus Toxoid / Q000276:immunology; D015215:Zidovudine / Q000627:therapeutic use
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D013745:Tetanus Toxoid; D015215:Zidovudine