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

病毒性性传播感染是一个重大的健康负担，特别是妇女保护自己免受感染的选择有限。2型单纯疱疹病毒（HSV-2）和人类免疫缺陷病毒（HIV）是两种最普遍的病毒性性传播感染。这两种感染都无法治愈，也无法用现有疫苗预防。两者都对生殖健康有严重的后遗症和影响。虽然艾滋病毒和2型单纯疱疹病毒感染已被证明彼此高度相关，但人们一直认为，感染每一种病毒可能是感染另一种病毒的危险因素。虽然行为改变和持续使用避孕套似乎都能预防艾滋病毒，但没有任何预防2型单纯疱疹病毒的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2型单纯疱疹病毒的生物学特性——病毒脱落发生在生殖器区域的广泛解剖区域这一事实——表明避孕套在预防2型单纯疱疹病毒传播方面的效果可能不如预防通过尿道和宫颈分泌物传播的性传播感染。在动物模型中，壬苯醇醚-9似乎对预防HSV-2感染有效，然而，对壬苯醇醚-9在预防人类HSV-2感染方面的作用知之甚少。这项AIDS-FIRCA提案的主要目的是确定2型单纯疱疹病毒感染是否是HIV感染的独立危险因素，并确定阴道内使用壬氧醇醚-9在预防2型单纯疱疹病毒感染中的作用。该提案概述了对在津巴布韦哈拉雷Spilhaus计划生育诊所就诊的1200名未感染艾滋病毒的妇女进行的为期3年的前瞻性队列研究。将获得基线临床、微生物学和实验室数据，包括艾滋病毒和2型单纯疱疹病毒血清学检测。如果我们确定感染2型单纯疱疹病毒会增加对艾滋病毒的易感性，并且壬苯醇醚-9可以预防2型单纯疱疹病毒的传播，我们将发现一种可改变的艾滋病毒危险因素，以及一种预防2型单纯疱疹病毒感染及其伴随的后遗症的廉价方法。通过简单地在津巴布韦已建立的三期试验中增加一管血液和一项诊断测试，这里提出的研究可能会回答这些重要问题。

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.