Gisolf E H, Enting R H, Jurriaans S, de Wolf F, van der Ende M E, Hoetelmans R M, Portegies P, Danner S A
National AIDS Therapy Evaluation Center, Amsterdam, The Netherlands.
AIDS. 2000 Jul 28;14(11):1583-9. doi: 10.1097/00002030-200007280-00014.
To assess the HIV-1-RNA response and drug concentrations in cerebrospinal fluid (CSF) and serum during treatment with saquinavir (SQV)/ritonavir (RTV) or SQV/RTV plus stavudine (d4T) in HIV-1 -infected patients.
A multicentre, open-label, randomized controlled trial.
A total of 208 protease inhibitor (PI) and d4T-naive, HIV-1-infected patients were treated with RTV 400 mg twice daily and SQV 400 mg twice daily with or without d4T 40 mg twice daily. Intensification with reverse transcriptase inhibitors was allowed if serum HIV RNA remained above 400 copies/ml after 12 weeks. In 27 volunteers, CSF and serum HIV RNA were measured at baseline, weeks 12 and 48, using the Roche Amplicor and the ultrasensitive assay. In 22 patients, serum and CSF drug concentrations were determined at week 12.
The median baseline serum and CSF HIV-RNA concentrations were 4.81 and 3.21 log10 copies/ml, respectively. A difference in the proportion of patients with a CSF HIV-RNA level below the limit of quantification (< LLQ) after 12 weeks was found: four out of 14 (RTV/SQV) versus 12 out of 13 (RTV/SQV/d4T) (P = 0.001). The same results were found using the ultrasensitive assay. Patients with a baseline HIV-RNA level < LLQ in CSF remained < LLQ, regardless of the treatment regimen. Treatment with RTV/SQV alone was the only independent predictor of a CSF HIV-RNA level > LLQ at week 12 in logistic regression analysis (P = 0.005). CSF RTV and SQV concentrations were < LLQ in most patients.
RTV/SQV alone cannot suppress detectable CSF HIV-1-RNA levels to < LLQ after 12 weeks of treatment in the majority of patients. CSF drug concentrations of RTV and SQV < LLQ may explain the suboptimal antiretroviral effect in the CSF.
评估在接受沙奎那韦（SQV）/利托那韦（RTV）或SQV/RTV加司他夫定（d4T）治疗的HIV-1感染患者中，脑脊液（CSF）和血清中的HIV-1-RNA反应及药物浓度。
一项多中心、开放标签、随机对照试验。
总共208名未使用过蛋白酶抑制剂（PI）和d4T的HIV-1感染患者，接受每日两次400mg RTV和每日两次400mg SQV治疗，同时或不同时接受每日两次40mg d4T治疗。如果12周后血清HIV RNA仍高于400拷贝/ml，则允许加用逆转录酶抑制剂进行强化治疗。在27名志愿者中，使用罗氏Amplicor和超敏检测法在基线、第12周和第48周测量CSF和血清HIV RNA。在22名患者中，在第12周测定血清和CSF药物浓度。
基线时血清和CSF中HIV-RNA浓度中位数分别为4.81和3.21 log10拷贝/ml。发现12周后CSF中HIV-RNA水平低于定量下限（<LLQ）的患者比例存在差异：14名患者中有4名（RTV/SQV组），而13名患者中有12名（RTV/SQV/d4T组）（P = 0.001）。使用超敏检测法也得到相同结果。CSF中基线HIV-RNA水平<LLQ的患者无论治疗方案如何仍保持<LLQ。在逻辑回归分析中，单独使用RTV/SQV治疗是第12周时CSF中HIV-RNA水平>LLQ的唯一独立预测因素（P = 0.005）。大多数患者CSF中的RTV和SQV浓度<LLQ。
在大多数患者中，单独使用RTV/SQV治疗12周后无法将可检测到的CSF中HIV-1-RNA水平抑制至<LLQ。CSF中RTV和SQV浓度<LLQ可能解释了CSF中抗逆转录病毒效果欠佳的原因。
