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: 6947519
• 负责人: CAROLYN WESTER
• 金额: $ 13.4万
• 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/6947519
• 关键词: AIDS therapy; Africa; African; HIV infections; antiAIDS agent; clinical research; clinical trials; female; genital herpes; herpes simplex virus 2; human immunodeficiency virus 1; human subject; longitudinal human study; patient oriented research; virus DNA; virus RNA; virus load; women' s health

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、护理和治疗相关的临床试验，特别是与妇女健康相关的临床试验。 生殖器溃疡病 (GUD) 在助长 HIV-1 流行方面发挥着重要作用。 2 型单纯疱疹病毒 (HSV-2) 是全球 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 感染和传播风险增加有关。即使在高效抗逆转录病毒治疗 (HAART) 的情况下，HSV-2 是否会影响 HIV-1 生殖道的脱落尚不清楚。需要这些信息来确定影响接受 HAART 的女性 HIV-1 感染性的因素，并制定有关接受 H​​AART 的合并感染者抑制生殖器疱疹的建议。这项拟议的前瞻性观察队列研究将检验以下假设：HAART 对减少生殖道 HIV-1 DMA 的存在和数量的影响会因 HSV-2 疾病和/或生殖道脱落而降低。具体目标包括：(i) 评估基线时和开始 HAART 后 6 个月时妇女中 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系，(ii) 评估基线时和开始 HAART 后 6 个月时 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 HIV 感染女性中 HSV-2 血清流行率。 该研究计划招募 400 名准备在博茨瓦纳启动 HAART 的 HIV 感染妇女（200 名 HSV-2 血清阴性和 200 名 HSV-2 血清阳性）。将在基线时和开始 HAART 后 6 个月收集血液和生殖道标本并进行分析。