Montaner J S, DeMasi R, Hill A M
University of British Columbia, St Paul's Hospital, Vancouver, Canada.
AIDS. 1998 Mar 26;12(5):F23-8. doi: 10.1097/00002030-199805000-00003.
To determine the value of plasma HIV-1 RNA and CD4 cell count as predictors of the clinical benefit of antiretroviral treatment.
The CAESAR (Canada, Australia, Europe, South Africa) trial randomized 1840 patients [inclusion CD4 cell count, 25-250 x 10(6)/l] to add either placebo, lamivudine (3TC) or 3TC plus loviride in a double-blinded fashion to baseline treatments (zidovudine, zidovudine-didanosine or zidovudine-zalcitabine) for 1 year.
This analysis included 487 patients with data on CD4 cell count and HIV-1 RNA after 12-20 weeks of treatment and subsequent follow-up for clinical progression.
The correlation between 12-20-week change in CD4 cell count, HIV-1 RNA and progression to AIDS or death in the placebo group was used to predict the clinical benefit of the 3TC-containing arms of the trial, given their effects on CD4 cell count and HIV-1 RNA.
After 12-20 weeks of treatment, HIV-1 RNA fell by 0.37 log10 copies/ml in the 3TC arms versus a rise of 0.05 log10 copies/ml in the placebo arm. The 12-20-week CD4 cell count rose by 35 x 10(6)/l in the 3TC arm versus a fall of 8 x 10(6)/l in the placebo arm. After 12-20 weeks of treatment, a reduction in HIV-1 RNA of 1 log10 at 12-20 weeks predicted a 49% reduction in progression [hazard ratio (HR), 0.51; 95% confidence interval (CI), 0.30-0.87] and a rise in CD4 cell count of 50 x 10(6)/l predicted a 51% reduction in progression (HR, 0.49; 95% CI, 0.33-0.73). Using the model from the placebo arm, the rises in CD4 cell count and reductions in HIV-1 RNA during 3TC treatment predicted a 59% reduction in progression to AIDS or death. The observed clinical benefit was a 57% reduction in progression for the 3TC arms versus placebo (HR, 0.43; 95% CI, 0.26-0.71).
Rises in CD4 cell count and reductions in HIV-1 RNA were reliable in predicting the clinical benefit of 3TC in the CAESAR trial.
确定血浆HIV-1 RNA和CD4细胞计数作为抗逆转录病毒治疗临床获益预测指标的价值。
CAESAR（加拿大、澳大利亚、欧洲、南非）试验以双盲方式将1840例患者（入选时CD4细胞计数为25 - 250×10⁶/l）随机分为在基线治疗（齐多夫定、齐多夫定-去羟肌苷或齐多夫定-扎西他滨）基础上加用安慰剂、拉米夫定（3TC）或3TC加洛匹那韦，治疗1年。
本分析纳入了487例在治疗12 - 20周后有CD4细胞计数和HIV-1 RNA数据且随后进行临床进展随访的患者。
利用安慰剂组治疗12 - 20周时CD4细胞计数、HIV-1 RNA的变化与进展至艾滋病或死亡之间的相关性，鉴于含3TC治疗组对CD4细胞计数和HIV-1 RNA的影响，来预测该试验含3TC治疗组的临床获益。
治疗12 - 20周后，3TC治疗组HIV-1 RNA下降0.37 log₁₀拷贝/ml，而安慰剂组上升0.05 log₁₀拷贝/ml。3TC治疗组治疗12 - 20周时CD4细胞计数上升35×10⁶/l，而安慰剂组下降8×10⁶/l。治疗12 - 20周后，12 - 20周时HIV-1 RNA降低1 log₁₀预测进展降低49%[风险比（HR），0.51；95%置信区间（CI），0.30 - 0.87]，CD4细胞计数上升50×10⁶/l预测进展降低51%（HR，0.49；95% CI，0.33 - 0.73）。使用安慰剂组的模型，3TC治疗期间CD4细胞计数上升和HIV-1 RNA降低预测进展至艾滋病或死亡降低59%。观察到的临床获益是3TC治疗组与安慰剂组相比进展降低57%（HR，0.43；95% CI，0.26 - 0.71）。
在CAESAR试验中，CD4细胞计数上升和HIV-1 RNA降低在预测3TC的临床获益方面是可靠的。
