Acylovir to prevent HIV acquisition in HSV-2+persons

描述：（由申请人提供）单纯疱疹2型（HSV-2）是 生殖器溃疡的主要原因，也是最普遍的性疾病之一。 在全球传播的疾病。同样，超过20项研究发现HSV-2 感染是艾滋病毒感染的风险因素，总体相对风险 在更严格的研究中是2.1最近一项关于艾滋病毒不和谐夫妇的研究 来自乌干达Rakai的研究表明， HIV阳性伴侣、易感伴侣中的HSV-2感染增加了 每个接触者感染艾滋病毒的风险是5倍。尽管这些流行病 数据是，需要进行干预试验，以确定临床和公众 这些发现的健康意义。这项建议是为了进行一项 概念验证、随机、双盲、安慰剂对照试验，以评估 每日使用阿昔洛韦抑制HSV-2对HIV感染者的疗效 两组HSV-2流行率高，HIV感染风险高： 赞比亚和津巴布韦的异性恋妇女和男男性行为者（MSM） 在美国和秘鲁。假设每天服用标准剂量的阿昔洛韦 每日两次400毫克将使异性恋妇女和男男性行为者的艾滋病发病率降低50% 通过降低临床和亚临床HSV-2再激活率。的 具体目的是：1）测量每日通用阿昔洛韦400 mg的疗效 PO bid预防HSV-2血清阳性、HIV阴性患者感染HIV 2）确定艾滋病病毒感染高危人群中的异性恋妇女和男男性行为者; 每日两次无环鸟苷抑制治疗对降低频率的影响 生殖器溃疡和亚临床HSV-2再激活的HSV-2血清阳性， 艾滋病毒阴性的人;和3）评估坚持每天两次阿昔洛韦 在HSV-2血清阳性、HIV阴性人群中进行抑制性治疗。共 将在5个研究中心入组1100名女性和1100名MSM，并随访平均 18个月的艾滋病毒感染事件。这项干预试验将直接 回答HSV-2感染增加对HIV易感性的程度 感染，以及HSV-2血清阳性人群中HIV发病率的相对降低 每天接受抑制性抗病毒治疗的人。阿昔洛韦有一个 对于广泛的STD治疗来说，安全性是可接受的，并且是廉价的， 宽容。鉴于全世界HSV-2感染率很高， 艾滋病毒的风险，这种方法可以有很大的公共卫生的重要性， 提供一种安全、可接受和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MSM之间的易感性。

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.