HIV TRIALS

艾滋病毒试验

• 批准号: 5201304
• 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/5201304
• 关键词: 2'3' dideoxyinosine; AIDS therapy; HIV infections; antiAIDS agent; antiviral agents; biomarker; clinical trials; combination chemotherapy; helper T lymphocyte; human immunodeficiency virus 1; human subject; human therapy evaluation; human tissue; mutagens; polymerase chain reaction; virus load; zidovudine

Among various endpoints currently used in the setting of HlV-1 infection, CD4 cell count represents the most extensively studied surrogate marker and might be predictive of the clinical effects of antiretroviral therapy. In some situations, it is highly correlated with clinical outcome at various points of time of antiretroviral therapy. However, it does not always correlate with clinical events, suggesting that the benefits of antiretroviral therapy may be due, at least in part, to factors not reflected in the effect of antiretroviral therapy on CD4 cell counts. In this regard, there are data suggesting that viral load represents a major determinant of the severity of HlV-1 related diseases and is associated with the stage and progression of immunological deterioration. HIV-1 particle numbers determined by using the polymerase chain reaction 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. It has recently been shown that therapy with simultaneous administration of zidovudine and didanosine provides more sustained elevation in CD4 cells than alternating therapy with the two agents over a time period of one year, suggesting that the dosing schedule of anti-HIV-1 drugs can be an important variable. In this study, we examined the changes in viremia levels and the development of drug-related mutations in 26 patients with symptomatic HIV-1 infection participating on a randomized trial comparing an alternating or simultaneous regimen of AZT and ddI therapy. Patients on both arms had significant reduction in serum RNA copies from baseline throughout the two years of the study. Significant differences between the two arms were demonstrated over the first 2-3 months of therapy. Analyses employing the nested PCR method revealed that the emergence of the ddI- related Leu74/EVal mutation was significantly blocked in both regimens while that of the AZT-related mutation at codon 215 was not affected. Determination of the overall durability of the anti-viremic effect of the alternating and simultaneous regimens of AZT and ddl and clinical implications of the results require further research.

在目前用于HIV-1感染的各种终点中， CD 4细胞计数是研究最广泛的替代标志物 并且可能预测抗逆转录病毒治疗的临床效果。 在某些情况下，它与临床结果高度相关， 抗逆转录病毒治疗的不同时间点。但不 总是与临床事件相关，这表明 抗逆转录病毒疗法可能是由于，至少部分是由于， 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，有数据表明，病毒载量是一个主要的 HIV-1相关疾病严重程度的决定因素， 与免疫恶化的阶段和进展有关。HIV-1 通过使用聚合酶链式反应测定的颗粒数具有 据报道，反映了病毒血症状态和病毒载量的个人， HIV-1感染，并可能作为一个潜在的临床指标，以监测 疾病进程和抗逆转录病毒治疗的有效性。 最近的研究表明，同时给药的治疗 齐多夫定和去羟肌苷的联合应用可更持续地升高CD 4 细胞，而不是在一段时间内用两种药物交替治疗， 一年，这表明抗HIV-1药物的给药时间表可以 一个重要的变量。在这项研究中，我们检查了病毒血症的变化， 水平和药物相关突变的发展，26例患者， 有症状的HIV-1感染者参加了一项随机试验， AZT和ddI交替或同时治疗方案。病人 两组的血清RNA拷贝均较基线显著降低 在两年的研究中。显著性差异 在治疗的前2-3个月内证明了双臂。分析 采用巢式PCR方法显示，ddI- 两种方案均显著阻断了相关的Leu 74/EVal突变 而与AZT相关的215位密码子突变则不受影响。 测定本发明的组合物的抗病毒血症作用的总体耐久性。 AZT和ddl的交替和同时方案以及临床 这些结果的影响需要进一步研究。