Quantification of HIV‐1 virus load under zidovudine therapy in patients with symptomatic HIV infectionrelation to disease progression
作者:
Jean-Michel Molina,
Françoise Ferchal,
Sylvie Chevret,
Véronique Barateau,
Christelle Poirot,
Frédéric Morinet,
Jacques Modai,
期刊:
AIDS
(OVID Available online 1994)
卷期:
Volume 8,
issue 1
页码: 27-34
ISSN:0269-9370
年代: 1994
出版商: OVID
关键词: HIV;plasma viraemia;cellular viraemia;CD4;CD8;p24antigen
数据来源: OVID
摘要:
ObjectiveTo measure changes in HIV-1 virus load following zidovudine therapy, and to investigate the relationship between these changes and clinical progression.DesignProspective study of 18 symptomatic, zidovudine-naive patients, with CD4 count < 350x106/l.MethodsThe following parameters were measured at each visit, before zidovudine therapy, after 1 month of therapy, and every 3 months thereafter. HIV-1 virus load in peripheral blood was determined by serum immune complex-dissociated HIV-1 p24antigen (ICD-p24Ag), quantitative plasma and cellular viraemia. A virologic response under zidovudine was defined as >50% decrease in ICD-p24Ag levels or > 1 log10decrease in plasma or cellular viraemia litres from baseline values. CD4 and CD8 cell counts, and β2-microglobulin levels were also measured. Disease progression was defined as the time to a new AIDS-defining event or death.ResultsAt enrolment, 13 out of 18 (72%) patients had positive ICD-p24Ag and positive plasma viraemia, with a mean of 44 median tissue culture infective dose (TCID50per ml; all patients had positive cellular viraemia with a mean TCID50of 230 per 106/l cells. Median CD4 cell count was 43 x 106/l. Ten patients developed a new AIDS-defining event and eight died during a median follow-up of 15 months on zidovudine. Baseline prognostic markers for development of a new AIDS-defining event included ICD-p24Ag, CD4 and CD8 cell counts, but only CD4 cell count remained predictive on multivariate analysis (P= 0.003). When each laboratory marker was analysed as a time-dependent covariate, only CD4 (P= 0.002) and CD8 (P= 0.001) cell counts predicted the occurrence of a new AIDS-defining event. Eight out of 13 (61.5%) patients had an ICD-p24Ag response, and seven out of 13 (54%) a plasma viraemia response, but only cellular viraemia responders (five out of 18; 28%) had a 5.6-fold decrease in their risk of developing an AIDS-defining event (90% confidence interval, 1–33;P= 0.05) None of these markers correlated with survival.ConclusionsPlasma viraemia and ICD-p24Ag, while providing useful short-term markers of zidovudine antiviral activityin vivo, do not correlate with disease progression in patients with advanced HIV infection. CD4 cell count remained the best initial and time-dependent predictor for development of new AIDS-defining events. Interestingly, a high CD8 cell count and a decrease in cellular viraemia litres also appear to be predictive of improved clinical outcome in this population.
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