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.
