Asymptomatic HIV infection is characterized by rapid turnover of HIV RNA in plasma and lymph nodes but not of latently infected lymph-node CD4+ T cells.
OBJECTIVE
To study the kinetics of plasma viraemia and HIV-infected lymph-node cells in stable asymptomatic HIV infection with high CD4+ T-cell counts.


METHODS
Nine asymptomatic HIV-infected patients with stable CD4+ T-cell counts (510-1350 x 10(6)/l) were treated with a triple-drug combination. Plasma viraemia was determined at days 0, 3, 7, 10, 14, 21 and 28 of treatment [Roche polymerase chain reaction (PCR) and ultrasensitive PCR assay]. Sequential lymph-node biopsies were examined in four patients before and after 4 weeks of treatment. Productively infected cells were counted in lymph-node sections (in situ hybridization). The infection rates of FACS-sorted CD4+ lymph-node T cells and the expression of single-spliced, double-spliced and full-length HIV transcripts were determined.


RESULTS
HIV plasma RNA half-lives ranged from 1.4 to 2.7 days. Viral turnover varied between 0.07 and 7.54 x 10(8) copies per day. The number of productively infected lymph-node cells as well as the amount of extracellular virus in germinal centres was markedly reduced during treatment, paralleled by a clearance of single-spliced, double-spliced and full-length HIV transcripts from CD4+ lymph-node T cells. Plasma viraemia remained detectable with an ultrasensitive PCR assay in three out of four patients. The percentage of lymph-node CD4+ T cells harbouring proviral DNA decreased only slightly.


CONCLUSIONS
The kinetics of HIV replication are rapid in stable asymptomatic infection, and the magnitude of replication varies considerably. Productively infected lymph-node cells and extracellular virus in germinal centres undergo a rapid turnover, whereas latently infected CD4+ T cells have a lower rate of turnover. The latter may contribute substantially to viral persistence during therapy.
Stellbrink
H J
HJ
Medical Department, Eppendorf University Hospital, Hamburg, Germany.
van Lunzen
J
J
Hufert
F T
FT
Fröschle
G
G
Wolf-Vorbeck
G
G
Zöllner
B
B
Albrecht
H
H
Greten
H
H
Racz
P
P
Tenner-Racz
K
K
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D004279:DNA, Viral / Q000235:genetics / Q000378:metabolism; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D017403:In Situ Hybridization; D007700:Kinetics; D008198:Lymph Nodes / Q000821:virology*; D008297:Male; D008875:Middle Aged; D011533:Proviruses / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000097:blood* / Q000235:genetics / Q000378:metabolism*; D014766:Viremia / Q000276:immunology / Q000821:virology; D014779:Virus Replication
D019380:Anti-HIV Agents; D004279:DNA, Viral; D012333:RNA, Messenger; D012367:RNA, Viral