Response of Genital Tract HIV-1 to HAART: Role of HSV-2?

生殖道 HIV-1 对 HAART 的反应：HSV-2 的作用？

• 批准号: 7432616
• 负责人: CAROLYN WESTER
• 金额: $ 13.41万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-06-01 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7432616
• 关键词: AIDS prevention; African; Anti-Retroviral Agents; Blood; Botswana; Caring; Cells; Clinic; Cohort Studies; Communicable Diseases; Conduct Clinical Trials; DNA; Disease; Enrollment; Ensure; Epidemic; Genital system; Goals; HIV Infections; HIV-1; Highly Active Antiretroviral Therapy; Human Herpesvirus 2; Individual; Infection; Plasma; Play; RNA; Recommendation; Risk; Role; Screening procedure; Seroprevalences; Specimen; Testing; Ulcer; Woman; Women' s Health; antiretroviral therapy; cohort; design; genital herpes; prospective; response; transmission process

DESCRIPTION (provided by applicant): The applicant's long-term goals are to conduct clinical trials related to HIV prevention, care, and treatment in the African context, particularly with respect to women's health. Genital ulcer disease (GUD) plays an important role in fueling the HIV-1 epidemic. Herpes simplex virus type 2 (HSV-2) is an increasingly important cause of GUD around the world and has been associated with increased HIV-1 genital tract shedding and increased risk of HIV-1 acquisition and transmission. It is not known whether HSV-2 influences HIV-1 genital tract shedding even in the context of highly active antiretroviral therapy (HAART). This information is needed to determine factors influencing HIV-1 infectiousness among women on HAART as well as to formulate recommendations regarding genital herpes suppression among co-infected individuals on HAART. This proposed prospective observational cohort study will test the hypothesis that the effect of HAART on decreasing the presence and quantity of genital tract HIV-1 DMA is reduced by the presence of HSV-2 disease and/or genital tract shedding. Specific aims include: (i) Evaluating the association between HSV-2 serostatus and presence and quantity of genital tract cell-associated HIV-1 DNA among women at baseline and at 6 months post-HAART initiation, (ii) Evaluating the association between genital tract HSV-2 DNA and HIV-1 DNA among HSV-2 / HIV-1 coinfected women at baseline and at 6 months post-HAART initiation, and (iii) Determining HSV-2 seroprevalence among women with advanced HIV-infection. The study plans to enroll 400 HIV-infected women preparing to initiate HAART in Botswana (200 HSV-2 seronegative and 200 HSV-2 seropositive). Blood and genital tract specimens will be collected and analyzed at baseline and 6 months after HAART initiation.

描述（由申请人提供）：申请人的长期目标是在非洲开展与艾滋病毒预防、护理和治疗有关的临床试验，特别是在妇女健康方面。 生殖器溃疡病（GUD）在助长HIV-1流行方面起着重要作用。单纯疱疹病毒2型（HSV-2）是全球GUD的一个日益重要的原因，并与HIV-1生殖道脱落增加以及HIV-1获得和传播风险增加有关。目前尚不清楚HSV-2是否影响HIV-1生殖道脱落，即使在高效抗逆转录病毒治疗（HAART）的背景下。需要这些信息来确定影响HAART妇女中HIV-1感染的因素，以及制定关于HAART合并感染者生殖器疱疹抑制的建议。这项拟定的前瞻性观察性队列研究将检验HAART减少生殖道HIV-1 DMA存在和数量的作用因HSV-2疾病和/或生殖道脱落而降低的假设。具体目标包括：（i）评价基线时和HAART开始后6个月时女性中HSV-2血清状态与生殖道细胞相关HIV-1 DNA的存在和数量之间的关联，（ii）评价基线时和HAART开始后6个月时HSV-2 / HIV-1合并感染女性中生殖道HSV-2 DNA与HIV-1 DNA之间的关联，和（iii）确定晚期HIV感染妇女中HSV-2血清阳性率。 该研究计划在博茨瓦纳招募400名准备开始HAART的HIV感染妇女（200名HSV-2血清阴性和200名HSV-2血清阳性）。将在基线和HAART开始后6个月采集血液和生殖道标本并进行分析。