Kinetics of response in lymphoid tissues to antiretroviral therapy of HIV-1 infection.
In lymphoid tissue, where human immunodeficiency virus-type 1 (HIV-1) is produced and stored, three-drug treatment with viral protease and reverse transcriptase inhibitors markedly reduced viral burden. This was shown by in situ hybridization and computerized quantitative analysis of serial tonsil biopsies from previously untreated adults. The frequency of productive mononuclear cells (MNCs) initially diminished with a half-life of about 1 day. Surprisingly, the amount of HIV-1 RNA in virus trapped on follicular dendritic cells (FDCs) decreased almost as quickly. After 24 weeks, MNCs with very few copies of HIV-1 RNA per cell were still detectable, as was proviral DNA; however, the amount of FDC-associated virus decreased by >/=3.4 log units. Thus, 6 months of potent therapy controlled active replication and cleared >99.9 percent of virus from the secondary lymphoid tissue reservoir.
Cavert
W
W
Department of Microbiology, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
Notermans
D W
DW
Staskus
K
K
Wietgrefe
S W
SW
Zupancic
M
M
Gebhard
K
K
Henry
K
K
Zhang
Z Q
ZQ
Mills
R
R
McDade
H
H
Schuwirth
C M
CM
Goudsmit
J
J
Danner
S A
SA
Haase
A T
AT
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D004279:DNA, Viral / Q000032:analysis; D003713:Dendritic Cells / Q000166:cytology / Q000821:virology*; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000627:therapeutic use; D015497:HIV-1 / Q000187:drug effects* / Q000302:isolation & purification / Q000502:physiology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D017403:In Situ Hybridization; D007700:Kinetics; D019259:Lamivudine / Q000627:therapeutic use; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000821:virology*; D008264:Macrophages / Q000821:virology; D014066:Palatine Tonsil / Q000821:virology*; D011533:Proviruses / Q000235:genetics; D012367:RNA, Viral / Q000032:analysis; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D019438:Ritonavir / Q000627:therapeutic use; D019562:Viral Load; D014779:Virus Replication / Q000187:drug effects; D015215:Zidovudine / Q000627:therapeutic use
D019380:Anti-HIV Agents; D004279:DNA, Viral; D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D015215:Zidovudine; D019438:Ritonavir