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

病毒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。 单纯疱疹病毒2型（HSV-2）和人类免疫缺陷病毒（HIV）是两种最常见的病毒性性STI。 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，但已假定感染每种病毒可能是感染另一种病毒的风险因素。 虽然行为改变和持续使用避孕套似乎可以预防艾滋病毒，但没有有效的HSV-2预防策略。 虽然缺乏有效的预防策略可能部分反映了迄今为止研究的不足，但HSV-2的生物学-病毒脱落发生在生殖器区域的广泛解剖区域-表明避孕套预防HSV-2传播的效果可能不如预防与尿道和宫颈分泌物传播相关的性传播感染。 壬苯醇醚-9在动物模型中似乎有效预防HSV-2感染，然而，关于壬苯醇醚-9在预防人类HSV-2感染中的作用知之甚少。该AIDS-FIRCA提案主要旨在确定HSV-2感染是否是HIV获得的独立风险因素，并确定阴道内使用壬苯醇醚-9预防HSV-2获得的效果。 该提案概述了对津巴布韦哈拉雷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3年前瞻性队列研究。 将获得基线临床、微生物学和实验室数据，包括HIV和HSV-2血清学检测。 如果我们确定HSV-2感染增加了对HIV的易感性，并且壬苯醇醚-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感染及其伴随后遗症的廉价方法。 通过简单地在津巴布韦的一个已建立的III期试验中增加一管血液和一个诊断测试，这里提出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.