Monitoring HAART in HIV-infected parents in Thailand

描述（由申请人提供）：高效抗逆转录病毒疗法（HAART）的实施导致HIV相关死亡率和发病率的大幅下降。然而，伴随这一重要进展而来的是一个监测和决策过程，其复杂性对医疗保健系统提出了挑战，特别是在有大量艾滋病毒感染患者和相对有限的财政和卫生保健资源的地区。目前的指南强调最大和持久的病毒载量（VL）抑制。然而，虽然成功的治疗是通过恢复免疫力来证明的，但治疗失败通常被定义为无法维持无法检测到的病毒载量，而不考虑免疫功能。这种情况通常会导致治疗切换的快速顺序，从而随着时间的推移缩小治疗选择。主要由患者免疫恢复驱动的监测策略很可能在预防疾病进展方面同样有效，将减少HAART方案的变化，并且将相当简单和具有成本效益。主要目的是比较基于VL （VL- s）的标准抗逆转录病毒监测策略与基于CD4+细胞计数（CD4- s）的更简单策略的临床结果。一个重要的次要目标是比较这两种策略保留治疗方案的能力。拟议的研究是一项多中心、III期、随机、非劣效性试验，比较泰国接受含pi方案治疗的抗逆转录病毒初始免疫功能低下成人中VL-S与CD4-S的差异。这项研究将在30个研究地点进行，研究人群将是700名感染艾滋病毒的女性或男性。指标病例将是在母婴预防计划中筛查的妇女和/或其伴侣，CD4+ T细胞计数在100至250/mm3之间。对于女性，将在分娩后进行随机分组。最初的HAART方案将是ZDV+3TC+因地那韦/利托那韦。在VL- s下，当VL高于2000 copies/ml时考虑切换；在CD4- s下，当观察到CD4+细胞计数相对于峰值下降超过30%时，考虑转换。监测策略比较的主要终点是临床失败，定义为确认CD4计数低于50/ mm3，首次或新的艾滋病定义事件，或死亡。次要终点是用尽的药物数量，考虑到交叉耐药突变和共同毒性。试点药代动力学亚研究将评估研究人群中的药物水平。

DESCRIPTION (provided by applicant): Implementation of highly active antiretroviral therapy (HAART) has led to a substantial decrease in HIV related mortality and morbidity. With this important advance, however, has come a monitoring and decision making process whose complexity challenges the medical care system, particularly in regions where there are large numbers of HIV-infected patients and relatively limited financial and health care resources. Current guidelines emphasize maximal and durable viral load (VL) suppression. However, while successful therapy is demonstrated by restoration of immunity, treatment failure is usually defined as the inability to maintain undetectable viral load, without regard to immune function. This situation often leads to a rapid sequence of therapeutic switches, thus narrowing therapeutic options over time. A monitoring strategy driven primarily by the patient's immune restoration would most likely be as effective in preventing disease progression, would lead to fewer changes in HAART regimens and would be considerably simpler and cost effective. The primary objective is to compare the clinical outcomes of the standard antiretroviral monitoring strategy based on VL (VL-S), with a simpler strategy based on CD4+ cell count (CD4-S). An important secondary objective is to compare the ability of these two strategies to preserve treatment options. The proposed study is a multi-center, Phase III, randomized, non-inferiority trial comparing VL-S with CD4-S among antiretroviral naive immunocompromised adults treated with a PI-containing regimen in Thailand. The study will take place at 30 study sites and the study population will be 700 HIV infected women or men. Index cases will be women screened within the mother-child prevention program, and/or their partners with a CD4+ T cell count between 100 and 250/mm3. For women, randomization will take place after delivery. The initial HAART regimen will be ZDV+3TC+indinavir/ritonavir. Under VL-S, switching is considered when VL rises above 2,000 copies/ml; Under CD4-S, switching is considered when a relative decline in the CD4+ cell count more than 30% from peak values is observed. The primary endpoint for monitoring strategy comparison is clinical failure, defined as confirmed CD4 count below 50/mm 3, first or new AIDS-defining event, or death. A secondary endpoint is the number of drugs exhausted, taking into account cross-resistance mutations and shared toxicities. A pilot pharmacokinetic sub study will evaluate drug levels in the study population.