HIV TRIALS

艾滋病毒试验

• 批准号: 3752383
• 负责人: H MITSUYA
• 金额: --
• 依托单位: DIVISION OF CANCER TREATMENT
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3752383
• 关键词: 2'3' dideoxyinosine; HIV infections; antiAIDS agent; antiviral agents; biomarker; clinical trials; combination chemotherapy; human immunodeficiency virus 1; human therapy evaluation; human tissue; longitudinal human study; mutagens; polymerase chain reaction; virus load; zidovudine

Among various clinical endpoints currently used in the setting of HIV-1 infection, CD4 cell count represents the most extensively studied marker and has been shown to explain some, but not all, of the clinical effects of antiretroviral therapy, indicating that the ultimate effect of antiretroviral therapy could be due to, at least in part, factors not reflected in the effect of antiretroviral therapy on CD4 cell counts. In this regard, there are considerable amounts of data indicating that the viral load represents a major determinant of the severity of HIV- 1 related diseases and is related to the stage and progression of immunological deterioration. HIV-1 particle numbers determined by using the polymerase chain reaction (PCR) have been reported to reflect viremia status and viral load in individuals with HIV-1 infection and may serve as a potential clinical marker to monitor the disease process and effectiveness of antiretroviral therapy. In the present study, we examined changes in viremia levels and development of drug-related mutations in patients with symptomatic HIV-1 infection randomized to receive an alternating regimen (A-AZT/ddI) or simultaneous regimen (S-AZT/ddI) of AZT and ddI therapy. Both A-AZT/ddI and S-AZT/ddI arms had a significant reduction in serum RNA copy numbers during the first 2-3 months of therapy [8-fold (p=0.0002) and 31-fold (p=0.0005) lower than at entry for A-AZT/ddI and S-AZT/ddI, respectively] as assessed by PCR following reverse transcription of viral RNA extracted from serum. The reduction was greater in S-AZT/ddI arm than in A-AZT/ddI arm (p=O.0051 both at 2 week and 9 week). After 1 year, the viremia level remained significantly lower in both arms [13-fold (p=O.0005) for A- AZT/ddI; 9-fold (p=0.0024) forS-AZT/ddI], but there was no difference between the arms (p=O.37). The reduction was still present after 2 years [19-fold (p=0.039) for A-AZT/ddI; 8-fold lower (p=0.014) for S-AZT/ddI, respectively].

在目前用于HIV-1背景的各种临床终点中， 感染时，CD 4细胞计数代表了最广泛研究的标志物 并已被证明可以解释一些，但不是全部， 抗逆转录病毒治疗的最终效果， 抗逆转录病毒治疗可能是由于，至少部分， 这反映在抗逆转录病毒治疗对CD 4细胞计数的影响中。在 在这方面，有大量的数据表明， 病毒载量是HIV- 1严重程度的主要决定因素 相关疾病，并与疾病的阶段和进展有关。 免疫恶化HIV-1颗粒数测定，使用 聚合酶链反应（PCR）已被报道反映病毒血症 HIV-1感染者的状态和病毒载量，并可能作为 监测疾病过程的潜在临床标志物， 抗逆转录病毒治疗的有效性。 在本研究中，我们检测了病毒血症水平的变化， 在有症状的HIV-1患者中发生药物相关突变 随机接受交替方案（A-AZT/ddI）的感染，或 AZT和ddI治疗的同步方案（S-AZT/ddI）。A-AZT/DDI 和S-AZT/ddI组血清RNA拷贝数显著减少， 在治疗的前2-3个月期间[8倍（p=0.0002）和31倍 （p=0.0005）分别低于入组时A-AZT/ddI和S-AZT/ddI] 如提取的病毒RNA逆转录后通过PCR评估的 从血清。S-AZT/ddI组的降低幅度大于A-AZT/ddI组 组（在2周和9周时p= 0.0051）。1年后，病毒血症水平 在两个组中仍然显著较低[对于A-13倍（p= 0.0005）， AZT/ddI; S-AZT/ddI为9倍（p=0.0024），但无差异 臂之间（p= 0.37）。2年后，减少仍然存在 [A-AZT/ddI为19倍（p=0.039）; S-AZT/ddI为8倍（p=0.014）， 分别）。