Molina J M, Ferchal F, Chevret S, Barateau V, Poirot C, Morinet F, Modai J
Department of Infectious Diseases, Hôpital Saint-Louis, Paris, France.
AIDS. 1994 Jan;8(1):27-33. doi: 10.1097/00002030-199401000-00005.
To measure changes in HIV-1 virus load following zidovudine therapy, and to investigate the relationship between these changes and clinical progression.
Prospective study of 18 symptomatic, zidovudine-naive patients, with CD4 count < 350 x 10(6)/l.
The 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 p24 antigen (ICD-p24 Ag), quantitative plasma and cellular viraemia. A virologic response under zidovudine was defined as > 50% decrease in ICD-p24 Ag levels or > 1 log10 decrease in plasma or cellular viraemia titres from baseline values. CD4 and CD8 cell counts, and beta 2-microglobulin levels were also measured. Disease progression was defined as the time to a new AIDS-defining event or death.
At enrolment, 13 out of 18 (72%) patients had positive ICD-p24 Ag and positive plasma viraemia, with a mean of 44 median tissue culture infective dose (TCID50) per ml; all patients had positive cellular viraemia with a mean TCID50 of 230 per 10(6)/l cells. Median CD4 cell count was 43 x 10(6)/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-p24 Ag, 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-p24 Ag 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.
Plasma viraemia and ICD-p24 Ag, while providing useful short-term markers of zidovudine antiviral activity in 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 titres also appear to be predictive of improved clinical outcome in this population.
测定齐多夫定治疗后HIV-1病毒载量的变化，并研究这些变化与临床进展之间的关系。
对18例有症状、未接受过齐多夫定治疗且CD4细胞计数<350×10⁶/l的患者进行前瞻性研究。
在每次就诊时，即在齐多夫定治疗前、治疗1个月后以及此后每3个月，测量以下参数。外周血中的HIV-1病毒载量通过血清免疫复合物解离的HIV-1 p24抗原（ICD-p24 Ag）、定量血浆和细胞病毒血症来确定。齐多夫定治疗下的病毒学反应定义为ICD-p24 Ag水平降低>50%或血浆或细胞病毒血症滴度较基线值降低>1 log₁₀。还测量了CD4和CD8细胞计数以及β2-微球蛋白水平。疾病进展定义为出现新的艾滋病定义事件或死亡的时间。
入组时，18例患者中有13例（72%）ICD-p24 Ag阳性且血浆病毒血症阳性，每毫升平均有44个中位数组织培养感染剂量（TCID50）；所有患者细胞病毒血症均为阳性，每10⁶/l细胞平均TCID50为230。CD4细胞计数中位数为43×10⁶/l。在接受齐多夫定治疗的中位随访15个月期间，10例患者出现了新的艾滋病定义事件，8例死亡。发生新的艾滋病定义事件的基线预后标志物包括ICD-p24 Ag、CD4和CD8细胞计数，但多变量分析时只有CD4细胞计数仍具有预测性（P = 0.003）。当将每个实验室标志物作为时间依赖性协变量进行分析时，只有CD4（P = 0.002）和CD8（P = 0.001）细胞计数可预测新的艾滋病定义事件的发生。13例患者中有8例（61.5%）出现ICD-p24 Ag反应，13例中有7例（54%）出现血浆病毒血症反应，但只有细胞病毒血症反应者（18例中有5例；28%）发生艾滋病定义事件的风险降低了5.6倍（90%置信区间，1 - 33；P = 0.05）。这些标志物均与生存率无关。
血浆病毒血症和ICD-p24 Ag虽然可提供齐多夫定体内抗病毒活性的有用短期标志物，但与晚期HIV感染患者的疾病进展无关。CD4细胞计数仍然是发生新的艾滋病定义事件的最佳初始和时间依赖性预测指标。有趣的是，高CD8细胞计数和细胞病毒血症滴度降低似乎也可预测该人群临床结局的改善。
