RAPID PLASMA VIRUS AND CD4-CELL TURNOVER IN HIV-1 INFECTION - EVIDENCE FOR AN ONLY TRANSIENT INTERRUPTION BY TREATMENT( T)

Objectives: To analyse the short-term kinetics of viral plasma RNA and CD4+ T cells numbers in patients with different initial CD4+ T-cell c ounts treated with different antiretroviral regimens. Methods: In 10 H IV-1-positive patients, in vivo kinetics of plasma HIV RNA and CD4+ T cells were studied during antiretroviral treatment. Lymphocyte subpopu lation analysis, quantitative polymerase chain reaction (PCR), p24 ant igen enzyme immunoassay (EIA) and beta(2)-microglobulin EIA were perfo rmed at days 0, 3, 7, 10, 14, 21 and 28 of treatment. One additional p atient served as a control. The resulting curves were fitted. Half-liv es were calculated using the time constant T of decrease or increase [ T-1/2 = ln(2)x T]. Calculations of virus and. CD4+ T-cell turnover wer e 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 trea tment and initial CD4+ T-cell count. The calculated peripheral blood v iral plasma RNA turnover varied between 0.02 and 55.8x10(8) copies/ml/ day and showed some negative correlation with initial CD4+ T-cell coun ts. CD4+ T-cell turnover estimates ranged from 0.01 to 7.5x10(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 p2 4 antigen-positive patients. beta(2)-microglobulin decreased until day 7-15 in all but one case and rapidly reincreased to pretreatment valu es. Conclusions: The kinetics of Virus and CD4+ T-cell turnover are un iformly rapid throughout a wide range of initial CD4+ T-cell counts. T he magnitude of vi rus 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 l ymphocyte turnover during treatment.