WOMEN'S HEALTH AGENDA

HIV-1感染有效治疗方法的开发与评价 受到临床终点的较长时间间隔和 相关性相对较差或缺乏疾病的病毒学标志物 进展 科学调查和治疗婴儿 潜在的毒性抗病毒药物是复杂的事实， 缺乏可靠的方法来诊断HIV-1感染， 由于母体HIV-1的被动传播， 抗体的 需要病毒学测定，其可以1）量化HIV-1载量 在实验性抗病毒药物治疗的患者的血液中， 提供药物疗效的早期评估，2）准确检测 婴儿HIV-1感染。 拟议研究的目的如下： 1.标准化并验证灵敏度、特异性和 商业聚合酶链反应（PCR）测定的重现性 HIV-1序列的非同位素检测。 2. HIV-1前病毒DNA和无细胞HIV-1的相关定量变化 血浆中的RNA水平，通过PCR和其他病毒学检测法测量， CD 4计数、疾病的临床分期和患者的临床结局 ACTG方案。 3.制定和评估标本处理程序和HIV-1 PCR检测试剂盒 用于外周血中HIV-1前病毒DNA序列的非同位素检测 血液单核细胞（PBMC）、脐带血单核细胞（CBMC）和 HIV-1血清阳性母亲的新生儿的干血斑。 为了实现这些目标，来自HIV-1血清阳性的血液标本 成人和新生儿将从一个或多个ACTU研究中心采集， 前瞻性处理，用于HIV-1 PCR检测和定量终点 稀释测定。 HIV-1 PCR批检测将使用 Perkin-Elmer/Gen-Probe HIV-1 PCR检测试剂盒和/或Roche HIV-1 PCR检测分析。 HIV-1 PCR敏感性初步评价后 和特异性，定性和定量HIV-1 PCR的能力， 与临床结果、CD 4计数和其他病毒学检测相关 （HIV-1培养，血清p24抗原水平），将进行前瞻性评价 在特定的儿科和成人ACTG方案中。

The development and evaluation of effective therapies for HIV-1 infection is limited by the long time interval to clinical endpoints and the relatively poor correlation or absence of virological markers for disease progression. Scientific investigation and treatment of infants with potentially toxic antiviral drugs are complicated by the fact that there is a lack of reliable methods to diagnose HIV-1 infection within the first several months of life due to passive transfer of maternal HIV-1 antibodies. Virological assays are needed that can 1) quantify HIV-1 load in the blood of patients on experimental antiviral drug therapies thereby providing an earlier assessment of drug efficacy and 2) accurately detect HIV-1 infection in infants. The proposed study has the following aims: 1. Standardize and validate the sensitivity, specificity, and reproducibility of commercial polymerase chain reaction (PCR) assays for the nonisotopic detection of HIV-1 sequences. 2. Correlate quantitative changes in HIV-1 proviral DNA and cell free HIV-1 RNA levels in plasma, as measured by PCR, with other virological assays, CD4 counts, clinical stage of disease, and clinical outcomes in patients on ACTG protocols. 3. Develop and evaluate specimen processing procedures and HIV-1 PCR assays for the nonisotopic detection of HIV-1 proviral DNA sequences in peripheral blood mononuclear cells (PBMC), cord blood mononuclear cells (CBMC) and dried blood spots of newborns of HIV-1 seropositive mothers. In order to achieve these aims, blood specimens from HIV-1 seropositive adults and newborns will be collected from one or several ACTU sites, and processed prospectively for HIV-1 PCR detection and quantitative endpoint dilution assays. HIV-1 PCR batch testing will be performed using the Perkin-Elmer/Gen-Probe HIV-1 PCR detection assays and/or the Roche HIV-1 PCR detection assay. After the initial evaluation of HIV-1 PCR sensitivity and specificity, the ability of qualitative and quantitative HIV-1 PCR to correlate with clinical outcome, CD4 counts, and other virological assays (HIV-1 culture, serum p24 antigen levels), will be evaluated prospectively within specific pediatric and adult ACTG protocols.