Genital Tract HIV Shedding in Cambodian Women

描述(由申请者提供)：该项目将主要在柬埔寨金边的西哈努克希望医院中心完成。医学博士Lim Kruy将担任外国现场调查员。这将是美国国立卫生研究院2号RO1 AI40350-06A2号拨款的延伸，颁奖日期为511103-4130108。该项目的目的是帮助查明与柬埔寨妇女生殖道艾滋病毒-1脱落症有关的因素。该项目将在柬埔寨获得越来越多的非专利抗逆转录病毒药物并且需要二级预防战略的情况下进行。与生殖道HIV-1RNA增加相关的情况可能会导致HIV-1传播的增加。识别和治疗这些情况可能有助于减少新的感染。此外，非专利抗逆转录病毒药物抑制生殖道HIV-1的效果尚不清楚。大多数关于抗逆转录病毒药物对生殖道HIV-1脱落的影响的研究都涉及B型亚型病毒，这种病毒在柬埔寨等资源匮乏的地区不太常见。该项目的具体目标是： 1)确定非专利抗逆转录病毒药物对生殖道HIV-1 E亚型脱落的影响，以及 2)确定在柬埔寨妇女队列中与生殖道HIV-1 E亚型脱落有关的因素，这些妇女具有显著的免疫损害、营养不良和合并疾病的高患病率。为了实现这些目标，40名在登记后开始抗逆转录病毒治疗的女性将接受为期18个月的纵向研究。在基线时，3个月、6个月、12个月和18个月的妇女将采集血液和生殖道样本，以测量HIV-1RNA水平。每位妇女还将接受CD4细胞的测量，并将对生殖器感染进行筛查，包括淋病、衣原体、滴虫、念珠菌阴道炎和细菌性阴道病。在每次研究访问中，将记录生殖器溃疡的存在，并将检测血液中的梅毒。HIV-1RNA将在血浆、宫颈阴道灌洗液中进行检测，并使用宫颈内管道的sno条样进行检测。回归分析将被用来确定与生殖道中艾滋病毒-1RNA的存在和脱落程度独立相关的因素。我们将分析随着时间的推移生殖道HIV-1脱落的危险因素与CD4、血浆HIV-1RNA、生殖器感染、用药依从性或其他并发条件的关系。被确定为与HIV-1RNA脱落有关的情况将被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.