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

说明（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）在世界范围内是GUD的一个日益重要的病因，并且与HIV-1生殖道脱落增加以及HIV-1获得和传播的风险增加有关。即使在高活性抗逆转录病毒治疗（HAART）的情况下，尚不清楚HSV-2是否影响HIV-1生殖道脱落。需要这些信息来确定在接受HAART治疗的妇女中影响艾滋病毒-1感染的因素，并制定关于在接受HAART治疗的合并感染者中抑制生殖器疱疹的建议。这项前瞻性观察队列研究将检验HAART对降低生殖道HIV-1 DMA的存在和数量的作用是否会因HSV-2疾病的存在和/或生殖道脱落而降低。具体目的包括：(i)评估基线和haart开始后6个月妇女中HSV-2血清状态与生殖道细胞相关HIV-1 DNA存在和数量之间的关系，（ii）评估基线和haart开始后6个月HSV-2 / HIV-1合并感染妇女中生殖道HSV-2 DNA和HIV-1 DNA之间的关系，以及（iii）确定晚期艾滋病毒感染妇女中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治疗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）。血液和生殖道标本将在基线和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.