Rapid plasma virus and CD4+ T-cell turnover in HIV-1 infection: evidence for an only transient interruption by treatment.
OBJECTIVE
To analyse the short-term kinetics of viral plasma RNA and CD4+ T cells numbers in patients with different initial CD4+ T-cell counts treated with different antiretroviral regimens.


METHODS
In 10 HIV-1 positive patients, in vivo kinetics of plasma HIV RNA and CD4+ T cells were studied during antiretroviral treatment. Lymphocyte subpopulation analysis, quantitative polymerase chain reaction (PCR), p24 antigen enzyme immunoassay (EIA) and beta 2-microglobulin EIA were performed at days 0, 3, 7, 10, 14, 21 and 28 of treatment. One additional patient served as a control. The resulting curves were fitted. Half-lives were calculated using the time constant T of decrease or increase [T1/2 = In(2) x T]. Calculations of virus and CD4+ T-cell turnover were multiplied by the total blood volume.


RESULTS
Viral plasma RNA half-life ranged from 1.1 to 5.1 days, independent of prior or actual treatment and initial CD4+ T-cell count. The calculated peripheral blood viral plasma RNA turnover varied between 0.02 and 55.8 x 10(8) copies/ml/day and showed some negative correlation with initial CD4+ T-cell counts. CD4+ T-cell turnover estimates ranged from 0.01 to 7.5 x 10(8) cells/day. Most patients showed an immediate reincrease of virus load after the nadir. Changes in HIV p24 antigen paralleled HIV plasma RNA in p24 antigen-positive patients. beta 2-microglobulin decreased until day 7-15 in all but one case and rapidly reincreased to pretreatment values.


CONCLUSIONS
The kinetics of virus and CD4+ T-cell turnover are uniformly rapid throughout a wide range of initial CD4+ T-cell counts. The magnitude of virus turnover varies considerably among individuals and appears to be inversely related to the initial CD4+ T-cell count. These data also argue for a rapid resumption of virus production and lymphocyte turnover during treatment.
Stellbrink
H J
HJ
Medizinische Kernklinik und Poliklinik, Eppendorf University Hospital, Hamburg, Germany.
Zöller
B
B
Fenner
T
T
Lichtenberg
G
G
van Lunzen
J
J
Albrecht
H
H
Thiele
H G
HG
Greten
H
H
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D016655:HIV Core Protein p24 / Q000097:blood; D006679:HIV Seropositivity / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1; D006801:Humans; D007700:Kinetics; D008297:Male; D012367:RNA, Viral / Q000097:blood; D019258:Saquinavir / Q000627:therapeutic use; D019562:Viral Load; D016047:Zalcitabine / Q000627:therapeutic use; D015215:Zidovudine / Q000627:therapeutic use; D001613:beta 2-Microglobulin / Q000032:analysis
D019380:Anti-HIV Agents; D016655:HIV Core Protein p24; D012367:RNA, Viral; D001613:beta 2-Microglobulin; D015215:Zidovudine; D016047:Zalcitabine; D019258:Saquinavir