A preliminary study of ritonavir, an inhibitor of HIV-1 protease, to treat HIV-1 infection.
A preliminary study of ritonavir, an inhibitor of HIV-1 protease, to treat HIV-1 infection.
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DOI：
10.1056/nejm199512073332204
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发表时间：
1995-12
期刊：
影响因子：
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通讯作者：
M. Markowitz;M. Saag;W. Powderly;A. Hurley;A. Hsu;J. Valdes;D. Henry;F. Sattler;Anthony F. La Marca;J. Leonard;D. Ho
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文献类型：
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作者：
M. Markowitz;M. Saag;W. Powderly;A. Hurley;A. Hsu;J. Valdes;D. Henry;F. Sattler;Anthony F. La Marca;J. Leonard;D. Ho
利托那韦是一种体外有效的人类免疫缺陷病毒1型（HIV-1）蛋白酶抑制剂，它是病毒粒子成熟和具有传染性所必需的。我们评估了利托那韦在HIV-1感染患者中的安全性和有效性。方法：在为期12周的试验中，我们以四种剂量中的一种口服利托那韦给62名患者，其中包括4周随机、安慰剂对照、双盲期和8周剂量盲期。我们通过血浆病毒血症和CD4细胞计数的连续测量来评估反应。结果52例患者完成了为期12周的试验。腹泻和恶心是最常见的副作用，血清甘油三酯和γ -谷氨酰转移酶水平可逆升高是最常见的实验室异常。利托那韦具有快速的抗病毒作用，在四个剂量组中，每毫升血浆中HIV-1 RNA拷贝数的平均最大减少量在0.86到1.18 log之间。治疗12周后，抗病毒效果部分维持，血浆病毒血症平均降低0.5 log。当我们在20名患者的亚组中使用更敏感的HIV-1 RNA检测时，我们发现血浆病毒血症平均降低了1.7 log。这种抗病毒效果在第12周部分持续，平均减少约1.1 log。在利托那韦治疗期间，患者的CD4细胞计数上升（在第4周和第12周分别增加74和83个细胞/立方毫米）。结论：蛋白酶抑制剂利托那韦耐受性良好，抗病毒效果显著，血浆病毒血症显著降低，CD4细胞计数显著升高。扩大利托那韦的临床试验是有必要的。
BACKGROUND Ritonavir is a potent inhibitor in vitro of human immunodeficiency virus type 1 (HIV-1) protease, which is needed for virions to mature and become infective. We assessed the safety and efficacy of ritonavir in patients with HIV-1 infection. METHODS We administered ritonavir orally to 62 patients in one of four dosages during a 12-week trial containing a 4-week randomized, placebo-controlled, double-blinded phase followed by an 8-week dose-blinded phase. We assessed the response with serial measurements of plasma viremia and serial CD4 cell counts. RESULTS Fifty-two patients completed the 12-week trial. Diarrhea and nausea were the most common side effects, and reversible elevations in serum triglyceride and gamma-glutamyltransferase levels were the most frequent laboratory abnormalities. Ritonavir had a rapid antiviral effect, with a mean maximal reduction in the number of copies of HIV-1 RNA per milliliter of plasma that ranged from 0.86 to 1.18 log in the four dosage groups. After 12 weeks of treatment, the antiviral effect was partially maintained, with a mean reduction in plasma viremia of 0.5 log. When we used a more sensitive assay for HIV-1 RNA in a subgroup of 20 patients, we found that plasma viremia decreased by a mean of 1.7 log. This antiviral effect was partly sustained at week 12, with a mean reduction of approximately 1.1 log. The patients' CD4 cell counts rose during treatment with ritonavir (median increase, 74 and 83 cells per cubic millimeter at weeks 4 and 12, respectively). CONCLUSIONS The protease inhibitor ritonavir is well tolerated and has a potent antiviral effect, as shown by substantial decreases in plasma viremia and significant elevations in CD4 cell counts. Expanded clinical trials of ritonavir are warranted.