HIV RISK REDUCTION THROUGH HSV-2 PREVENTION WITH N-9

病毒性性传播感染是一种严重的健康负担，尤其是妇女保护自己免受其侵害的选择有限。单纯疱疹病毒2型(HSV-2)和人类免疫缺陷病毒(HIV)是最流行的两种病毒性性传播疾病。这两种感染都不能治愈，也不能用现有的疫苗预防。两者都有严重的后遗症，并对生殖健康产生影响。虽然HIV和HSV-2感染已被证明彼此高度相关，但有人推测，两种病毒的感染都可能是另一种病毒感染的危险因素。尽管行为改变和持续使用避孕套似乎都能预防艾滋病毒，但尚未有针对HSV-2的预防策略被证明是有效的。虽然缺乏有效的预防策略可能在一定程度上反映了迄今为止研究的不足，但HSV-2的生物学--病毒在生殖器区域的广泛解剖区域发生--表明，避孕套在预防HSV-2传播方面的效果可能不如预防与通过尿道和宫颈分泌物传播有关的性传播感染。在动物模型中，unoxnol-9似乎对预防HSV-2感染有效，然而，对于其在人类预防HSV-2感染中的作用，人们知之甚少。这项AIDS-FIRCA建议的主要目的是确定HSV-2感染是否是HIV感染的独立危险因素，并确定经阴道使用壬醇-9在预防HSV-2感染方面的效果。这项提案概述了一项为期3年的前瞻性队列研究，研究对象是在津巴布韦哈拉雷的斯皮尔豪斯计划生育诊所就诊的1200名未感染艾滋病毒的妇女。将获得基线临床、微生物学和实验室数据，包括艾滋病毒和HSV-2血清学测试。如果我们确定感染HSV-2会增加对HIV的易感性，并且unoxnol-9可以防止HSV-2的传播，我们将揭示HIV的一个可改变的风险因素，以及预防HSV-2感染和随之而来的后遗症的廉价方法。只需在津巴布韦已建立的III期试验中增加一管血液和一项诊断测试，这里提议的研究可能会回答这些重要的问题。

Viral sexually transmitted infections (STIs) are a significant health burden and in particular, women have limited options to protect themselves against them. Herpes simplex virus type 2 (HSV-2) and human immunodeficiency virus (HIV) are two of the most prevalent viral STIs. Neither of these infections is curable, or preventable with available vaccines. Both have serious sequelae and implications for reproductive health. While HIV and HSV-2 infection have been demonstrated to be highly associated with each other, it has been postulated that infection with each virus may be a risk factor for infection with the other. Although both behavior change and the consistent use of condoms appear to protect against HIV, no prevention strategies for HSV-2 have been demonstrated to be effective. While this lack of effective prevention strategies may in part reflect the inadequacy of studies to date, the biology of HSV-2 -- the fact that viral shedding occurs over a wide anatomic area in the genital region -- suggests that condoms may be less effective for preventing transmission of HSV-2 than for preventing STIs associated with transmission through urethral and cervical secretions. Nonoxynol-9 appears effective in preventing HSV-2 infection in animal models, however, little is known about the effect of nonoxynol-9 in preventing HSV-2 infection in humans. This AIDS-FIRCA proposal is primarily aimed at determining if HSV-2 infection is an independent risk factor for HIV acquisition, and at defining the effect of intravaginal use of nonoxynol-9 in preventing HSV-2 acquisition. This proposal outlines a 3 year prospective cohort study of 1200 HIV uninfected women attending the Spilhaus family planning clinic in Harare, Zimbabwe. Baseline clinical, microbiologic, and laboratory data, including HIV and HSV-2 serologic tests will be obtained. If we establish that infection with HSV-2 increases susceptibility to HIV, and that nonoxynol-9 prevents transmission of HSV-2, we will have revealed a modifiable risk factor for HIV, as well as an inexpensive means of preventing HSV-2 infection and its attendant sequelae. By simply adding an additional tube of blood and a diagnostic test to an established phase III trial in Zimbabwe, the study being proposed here may answer these important questions.