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

描述(由申请人提供)：申请人的长期目标是在非洲范围内进行与艾滋病毒预防、护理和治疗有关的临床试验，特别是关于妇女健康的临床试验。生殖器溃疡疾病(GUD)在助长HIV-1流行方面发挥着重要作用。单纯疱疹病毒2型(HSV-2)是世界各地引起GUD的一个日益重要的原因，并与艾滋病毒-1生殖道脱落增加以及艾滋病毒-1感染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)的背景下也是如此。需要这些信息来确定影响接受HAART治疗的妇女感染HIV-1的因素，以及制定关于HAART联合感染患者中生殖器疱疹抑制的建议。这项拟议的前瞻性观察队列研究将检验这样一种假设，即HAART在减少生殖道HIV-1DMA存在和数量方面的作用因HSV-2疾病和/或生殖道脱落的存在而降低。具体目标包括：(1)评估基线和HAART开始后6个月妇女生殖道细胞相关HIV-1 DNA的存在和数量与HSV-2血清状态之间的关系；(2)评估HSV-2/HIV-1混合感染妇女在HAART基线和开始HAART后6个月生殖道HSV-2 DNA和HIV-1 DNA之间的关系；以及(3)确定晚期艾滋病毒感染妇女中HSV-2血清阳性率。这项研究计划招募400名准备在博茨瓦纳启动HAART的艾滋病毒感染妇女(200名HSV-2血清阴性和200名HSV-2血清阳性)。血液和生殖道样本将在基线和HAART开始后6个月收集和分析。

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.