Powderly W G, Saag M S, Chapman S, Yu G, Quart B, Clendeninn N J
Washington University School of Medicine, St. Louis, Missouri 63110, USA.
AIDS. 1999 Oct 1;13(14):1873-80. doi: 10.1097/00002030-199910010-00009.
Current potent antiretroviral therapy (using a protease inhibitor and two nucleoside reverse transcriptase inhibitors) produces a durable suppression of HIV replication in less than 75% of treated patients. Identification of predictors of successful therapy might allow the development of improved strategies to increase response rates.
We analyzed retrospectively the results from a multicenter, randomized, double-blind Phase III study of combination anti-HIV therapy with nelfinavir, zidovudine, and lamivudine to evaluate the relationship between virological response over 48 weeks of treatment to variables which could potentially serve as early predictors of long-term response. The goal was to produce long-term suppression of viral load to sensitive (<400 copies HIV RNA/ml) and ultrasensitive (<50 copies HIV RNA/ml) limits of quantification with the Amplicor PCR assay.
Baseline viral load, the change in viral load over the first 4 weeks of treatment, the 2 h post-dose nelfinavir levels and the time to respond to HIV RNA levels of <400 copies/ml and <50 copies/ml have the best predictive value in determining response and response duration. Patients who achieved very low viral nadirs (<50 copies HIV RNA/ml) had significantly longer responses than those who achieved nadirs of 50-400 copies HIV RNA/ml.
Parameters that can be measured easily at baseline or early after therapy is started can identify patients at high risk of failure with standard treatment. Such patients may be candidates for more aggressive therapy or for alternative strategies designed to improve outcome. In addition, these results support the use of ultra-sensitive HIV RNA assays to predict long-term outcome of anti-HIV therapy.
目前的强效抗逆转录病毒疗法（使用一种蛋白酶抑制剂和两种核苷类逆转录酶抑制剂）在不到75%的接受治疗的患者中能持久抑制HIV复制。确定成功治疗的预测因素可能有助于制定改进策略以提高应答率。
我们回顾性分析了一项多中心、随机、双盲的III期研究结果，该研究采用奈非那韦、齐多夫定和拉米夫定联合抗HIV治疗，以评估48周治疗期间病毒学应答与可能作为长期应答早期预测指标的变量之间的关系。目标是使用Amplicor PCR检测法将病毒载量长期抑制至敏感（<400拷贝HIV RNA/ml）和超敏感（<50拷贝HIV RNA/ml）定量下限。
基线病毒载量、治疗前4周病毒载量的变化、给药后2小时奈非那韦水平以及对HIV RNA水平<400拷贝/ml和<50拷贝/ml的应答时间在确定应答和应答持续时间方面具有最佳预测价值。病毒最低点极低（<50拷贝HIV RNA/ml）的患者的应答时间明显长于病毒最低点为50 - 400拷贝HIV RNA/ml的患者。
在基线或治疗开始后早期易于测量的参数可识别出标准治疗失败风险高的患者。此类患者可能适合更积极的治疗或旨在改善治疗结果的替代策略。此外，这些结果支持使用超灵敏HIV RNA检测法来预测抗HIV治疗的长期结果。
