EFFECTS OF COMBINED ANTIRETROVIRAL THERAPY ON COAGULATION FACTORS

联合抗逆转录病毒治疗对凝血因子的影响

• 批准号: 6123228
• 负责人: M E EYSTER
• 金额: $ 3.26万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6123228
• 关键词: HIV infections; antiAIDS agent; clinical research; coagulation factor IX; coagulation factor VIII; combination chemotherapy; hemophilia As; hemophilia B; human subject; human therapy evaluation; longitudinal human study; pharmacokinetics; platelet activation; platelet aggregation; protease inhibitor

Effects of Combination Antiretroviral Therapy including Indinavir Sulfate on Coagulation Factors, on Platelet Aggregation and on Factor VIII/IX in HIV-1 Seropositive patients with Hemophilia A or B. The objectives of this protocol are to assess whether, in the specific population being studied, a combined therapy of indinavir sulfate NRTIs induces changes in prospectively identified elements of the coagulation system. It is recognized apriori, that due to the nonfeasibility of having a group in which indinivar sulfate is not added to combination NRTI therapy, it will be impossible to determine what changes in the coagulation system, if any, would have been observed in the absence of indinivar sulfate. However, to help assess changes in the pharmacokinetic half-life and recovery of infused factor VIII, protease inhibitor-experienced HIV-1 seropositive hemophilia A patients will serve as a laboratory control group. We hypothesize that after 12 weeks of treatment, coadministration of indinavir sulfate and NRTIs to protease inhibitor-naive HIV-1 seropositive hemophilia A patients will decrease the pharmacokinetic half-life of infused factor VIII compared to pre-indinavir sulfate therapy baseline relative to changes observed in the laboratory control group. Secondarily, during a 52 week coadministration of indinavir sulfate and combination NTRI therapy to protease inhibitor-naive HIV-1 seropositive hemophilia patients after 12 weeks of treatment: the pharmacokinetic recovery of infused factor VIII in hemophilia A patients will be reduced, relative to changes observed in the laboratory control group; the pharmacokinetic half-life of infused factor IX in hemophilia B patients will be reduced and the pharmacokinetic recovery of infused factor IX in hemophilia B patients will be reduced.

包括硫酸因地那韦在内的抗逆转录病毒联合治疗对HIV-1血友病A或b血清阳性患者凝血因子、血小板聚集和因子VIII/IX的影响。本方案的目的是评估在研究的特定人群中，硫酸因地那韦NRTIs联合治疗是否会诱导凝血系统中预期确定的元素的变化。我们先验地认识到，由于在联合NRTI治疗中不添加硫酸因地瓦的组是不可行的，因此不可能确定在没有硫酸因地瓦的情况下，凝血系统会发生什么变化（如果有的话）。然而，为了帮助评估输注因子VIII的药代动力学半衰期和恢复的变化，蛋白酶抑制剂经历的HIV-1血清阳性血友病A患者将作为实验室对照组。我们假设，在治疗12周后，对蛋白酶抑制剂初始HIV-1血清阳性的A型血友病患者联合给予硫酸因地那韦和NRTIs，与硫酸因地那韦治疗前的基线相比，相对于实验室对照组观察到的变化，会降低输注因子VIII的药代动力学半衰期。其次，对蛋白酶抑制剂初始HIV-1血清阳性血友病患者治疗12周后，在52周的时间内，硫酸因地那韦联合NTRI治疗：a型血友病患者输注因子VIII的药代动力学恢复相对于实验室对照组的变化有所降低；B型血友病患者输注IX因子药代动力学半衰期缩短，B型血友病患者输注IX因子药代动力学恢复减慢。