Genital Tract HIV Shedding in Cambodian Women

描述（由申请人提供）：该项目将主要在柬埔寨金边的希望西哈努克医院中心进行。Dr. Lim Kruy，MD将担任国外研究中心研究者。这将是NIH补助金#2 RO 1 AI 40350 - 06 A2的扩展，授予日期为511103-4130108。该项目的目的是帮助确定与柬埔寨妇女生殖道HIV-1传播有关的因素。当柬埔寨越来越多地提供非专利抗逆转录病毒药物和需要二级预防战略时，将开展这一项目。与生殖道HIV-1 RNA增加相关的疾病可能导致HIV-1传播增加。识别和治疗这些疾病可能有助于减少新的感染。此外，抗逆转录病毒药物对抑制生殖道HIV-1的影响尚不清楚。大多数关于抗逆转录病毒药物对生殖道HIV-1脱落影响的研究涉及B亚型病毒，这种病毒在柬埔寨等资源贫乏的环境中不太常见。该项目的具体目标是： 1)确定通用抗逆转录病毒药物对生殖道HIV-1 E亚型脱落的影响， 2)在一组具有显著免疫功能低下、营养不良和合并症高患病率的柬埔寨妇女中，确定与生殖道HIV-1 E亚型脱落相关的因素。为了实现这些目标，40名妇女在登记后开始抗逆转录病毒治疗，将进行为期18个月的纵向研究。在基线、3个月、6个月、12个月和18个月时，将收集女性的血液和生殖道样本以测量HIV-1 RNA水平。每位妇女还将测量CD 4细胞，并筛查生殖器感染，包括淋病，衣原体，滴虫，念珠菌阴道炎和细菌性阴道病。在每次研究访视时，将记录生殖器溃疡的存在，并检测血液中的梅毒。将在血浆、宫颈阴道灌洗液中测量HIV-1 RNA，并使用宫颈管sno条采样。回归分析将用于确定与生殖道中HIV-1 RNA脱落的存在和程度独立相关的因素。我们将分析生殖道HIV-1随时间脱落的风险因素，这些风险因素与CD 4、血浆HIV-1 RNA、生殖器感染、药物依从性或其他并发症有关。确定为与HIV-1 RNA脱落相关的疾病将作为进一步研究的目标。

DESCRIPTION (provided by applicant): This project will be done primarily in Phnom Penh, Cambodia at the Sihanouk Hospital Center of HOPE. Dr. Lim Kruy, MD will be the foreign site investigator. This will be an extension of NIH Grant #2 RO1 AI40350- 06A2, award dates 511103-4130108. The purpose of this project is to help to identify the factors associated with genital tract HIV-1 shedding among Cambodian women. This project will occur when generic antiretroviral medications are increasingly available in Cambodia and strategies for secondary prevention are needed. Conditions associated with increases in genital tract HIV-1 RNA may lead to increases in HIV-1 transmission. Identifying and treating these conditions may help to reduce new infections. In addition, the effect of generic antiretroviral medications on suppressing genital tract HIV-1 is not known. Most studies of the effect of antiretroviral medications on genital tract HIV-1 shedding involve subtype B virus, which is less common in resource poor settings like Cambodia. The specific aims of this project are: 1) To determine the effect of generic antiretroviral medications on genital tract HIV-1 subtype E shedding, and 2) To determine the factors associated with genital tract HIV-1 subtype E shedding in a cohort of Cambodian women with a high prevalence of significant immunocompromise, malnutrition, and co-morbid conditions. To accomplish these aims, 40 women initiating antiretroviral therapy after enrollment will be followed in an 18-month longitudinal study. At baseline, 3 months, 6 months, 12 months, and 18 months women will have blood and genital tract specimens collected to measure HIV-1 RNA levels. Each woman will also have measurement of CD4 cells and will be screened for genital infections including gonorrhea, Chlamydia, trichomonas, Candida vaginitis, and bacterial vaginosis. At each study visit, the presence of genital ulcerations will be noted and blood will be tested for syphilis. HIV-1 RNA will be measured on plasma, cervicovaginal lavage fluid, and using sno-strip sampling of the endocervical canal. Regression analysis will be used to identify factors that are independently associated with the presence and degree of HIV-1 RNA shedding in the genital tract. We will analyze risk factors for genital tract HIV-1 shedding over time in relation to CD4, plasma HIV-1 RNA, genital infections, medication adherence, or other concurrent conditions. Conditions identified as being associated with HIV-1 RNA shedding will be targeted for further study.