Drusano G L, Stein D S
Department of Medicine, Albany Medical College, New York 12208, USA.
Antimicrob Agents Chemother. 1998 Feb;42(2):358-61. doi: 10.1128/AAC.42.2.358.
While CD4 cell counts are widely used to predict disease progression in human immunodeficiency virus (HIV)-infected patients, they are poorly explanatory of the progression to AIDS or death after the introduction of chemotherapy. Changes in HIV load (as measured by RNA PCR) have been shown to be a much better predictor of the risk of disease progression. Since the interrelationship of these markers is of great clinical interest, we modeled the time-averaged return of CD4 cell count and change in viral load subsequent to therapy with the HIV protease inhibitor indinavir. We found that CD4 cell return was significantly related to both the baseline CD4 count (r2 = 0.86, P < 0.001) and the decline in HIV RNA PCR-determined viral load (also referred to in this work as the HIV RNA PCR decline) (r2 = 0.60, P < 0.01). Simultaneously modeling both influences in a linked nonlinear model (r2 = 0.93, P < 0.001) demonstrated that (i) the starting number of CD4 cells accounted for the majority of the change in CD4 cell return and (ii) the return of CD4 cells attributable to viral load decrease was 50% of maximal with only a decrease of approximately 0.2 log of HIV RNA as modeled from the first 12 weeks of therapy. Much greater viral inhibition beyond that necessary for maximal CD4 cell return is possible. Given that HIV RNA PCR decline is more strongly linked to ultimate clinical course in HIV disease, our findings indicate that CD4 return is potentially misleading as an indicator of antiviral effect, since it is determined more by the starting CD4 value than by viral load decline and since near-maximal changes occur with minimal antiviral effect.
虽然CD4细胞计数被广泛用于预测人类免疫缺陷病毒（HIV）感染患者的疾病进展，但在引入化疗后，它们对艾滋病进展或死亡的解释能力较差。HIV载量的变化（通过RNA PCR测量）已被证明是疾病进展风险的更好预测指标。由于这些标志物之间的相互关系具有重要的临床意义，我们对使用HIV蛋白酶抑制剂茚地那韦治疗后CD4细胞计数的时间平均恢复情况以及病毒载量的变化进行了建模。我们发现，CD4细胞恢复与基线CD4计数（r2 = 0.86，P < 0.001）和HIV RNA PCR测定的病毒载量下降（在本研究中也称为HIV RNA PCR下降）（r2 = 0.60，P < 0.01）均显著相关。在一个关联非线性模型中同时对这两种影响进行建模（r2 = 0.93，P < 0.001）表明：（i）CD4细胞的起始数量占CD4细胞恢复变化的大部分；（ii）从治疗的前12周建模来看，仅HIV RNA下降约0.2 log时，病毒载量下降导致的CD4细胞恢复仅为最大值的50%。实现比最大CD4细胞恢复所需的更大程度的病毒抑制是可能的。鉴于HIV RNA PCR下降与HIV疾病的最终临床病程联系更为紧密，我们的研究结果表明，CD4恢复作为抗病毒效果的指标可能会产生误导，因为它更多地由起始CD4值而非病毒载量下降决定，而且在抗病毒效果最小的情况下会出现接近最大的变化。
