Acylovir to prevent HIV acquisition in HSV-2+persons

描述：(申请人提供)单纯疱疹病毒2型(HSV-2)是 生殖器溃疡的主要原因，也是最常见的性行为之一 世界范围内的传染病。一直以来，超过20项研究发现了HSV-2 感染是艾滋病毒感染的风险因素，总体相对风险 在更严格的研究中为2.1。最近对HIV不和谐夫妇的一项研究 来自乌干达Rakai的一项研究表明，在所有水平的艾滋病毒病毒载量 HIV阳性伴侣中，HSV-2感染在易感伴侣中增加 每名接触者感染艾滋病毒的风险是5倍。像这些流行病一样强大 数据是，需要一项干预试验来确定临床和公众 这些发现的健康意义。这项提案是为了进行一次 概念验证、随机、双盲、安慰剂对照试验 阿昔洛韦抑制单纯疱疹病毒2型感染HIV的疗效观察 HSV-2高流行率和高发HIV风险的两组人群： 赞比亚和津巴布韦的异性恋女性和男男性行为者(MSM) 在美国和秘鲁。假设每日标准剂量的阿昔洛韦 400 mg Bid将使异性恋妇女和男男性接触者的HIV发病率降低50% 通过降低临床和亚临床HSV-2复发率。这个 具体目标是：1)测量每日非专利阿昔洛韦400毫克的疗效 PO BID在预防HSV-2血清阳性和HIV阴性患者感染HIV中的作用 异性恋妇女和男男性接触者感染艾滋病毒的高危人群；2)确定 每日两次阿昔洛韦抑制治疗对减少频率的作用 在HSV-2血清阳性者中生殖器溃疡和亚临床HSV-2重新激活， HIV阴性者；以及3)评估每天服用两次阿昔洛韦的依从性 单纯疱疹病毒2型血清阳性、HIV阴性患者的抑制治疗。总计 1100名妇女和1100名男男性接触者将在5个地点登记，平均跟踪时间为 事件HIV感染18个月。这场干预试验将直接 回答HSV-2感染增加HIV易感性的程度 HSV-2血清阳性人群中HIV感染率的相对降低 每天接受抑制性抗病毒治疗的人。阿昔洛韦有一种 广泛的性传播疾病治疗的可接受的安全概况，并且价格低廉 耐受性很好。鉴于全球范围内单纯疱疹病毒2型的高感染率 对艾滋病毒的风险，这种方法可能通过以下方式对公共卫生产生重大影响 提供安全、可接受且具有成本效益的方法来减少艾滋病毒 高危HIV阴性异性恋者和男男性接触者的易感性。

DESCRIPTION: (provided by applicant) Herpes simplex type-2 (HSV-2) is the primary cause of genital ulcers, and one of the most prevalent sexually transmitted diseases worldwide. Consistently, over 20 studies have found HSV-2 infection to be a risk factor for HIV acquisition with an overall relative risk of 2.1 in the more rigorous studies. A recent study of HIV-discordant couples from Rakai, Uganda, has shown that at all levels of HIV viral load in the HIV-positive partner, HSV-2 infection in the susceptible partner increased the per-contact risk of acquisition of HIV 5-fold. As strong as these epidemiologic data are, an intervention trial is required to define the clinical and public health significance of these findings. This proposal is to conduct a proof-of-concept, randomized, double-blind, placebo-controlled trial to assess the efficacy of HSV-2 suppression with daily acyclovir on HIV acquisition among two groups with high rates of HSV-2 prevalence and high risk of incident HIV: heterosexual women in Zambia and Zimbabwe and men who have sex with men (MSM) in the U.S. and Peru. The hypothesis is that standard doses of daily acyclovir 400mg bid will reduce HIV incidence by 50 percent in heterosexual women and MSM by decreasing rates of clinical and subclinical HSV-2 reactivation. The specific aims are: 1) To measure the efficacy of daily generic acyclovir 400 mg PO bid in preventing HIV acquisition among HSV-2 seropositive, HIV-negative heterosexual women and MSM at high risk for HIV infection; 2) To determine the effect of twice daily acyclovir suppressive therapy on reducing the frequency of genital ulcers and subclinical HSV-2 reactivation among HSV-2 seropositive, HIV-negative persons; and 3) To assess adherence with twice daily acyclovir suppressive therapy among HSV-2 seropositive, HIV-negative persons. A total of 1100 women and 1100 MSM will be enrolled at 5 sites and followed for a mean of 18 months for incident HIV infection. This intervention trial will directly answer the extent to which HSV-2 infection increases susceptibility to HIV infection, and the relative reduction in HIV incidence among HSV-2 seropositive persons treated with daily suppressive antiviral therapy. Acyclovir has an acceptable safety profile for widespread STD treatment and is inexpensive and well-tolerated. Given high rates of HSV-2 infection worldwide in persons at risk for HIV, this approach could have great public health importance by providing a safe, acceptable, and cost-effective method to reduce HIV susceptibility among high-risk HIV-negative heterosexuals and MSM.