| Abstract |
In developing countries, many HIV-infected women do not have access to anti-retroviral therapy. Therefore, other interventions that can decrease HIV transmission and acquisition are particularly needed in resource-limited settings. It has been shown that several ulcerative and non-ulcerative sexually transmitted infections (STI) can upregulate HIV genital tract shedding. However, there are very few interventional studies to show that treatment of STIs leads to a decrease in genital tract viral load which may in turn decrease sexual transmission of HIV. Vaginal trichomoniasis has been associated with an increased risk of HIV seroconversion. There have been limited reports regarding the relationship between trichomoniasis and genital HIV viral burden. The purpose of this study is to determine whether treatment of trichomoniasis is associated with decreased genital HIV viral shedding and inflammation. The specific aims of the project are as follows: 1.To examine the effect of standard metronidazole treatment of trichomoniasis among HIV infected women on genital viral load. Our hypothesis is that trichomoniasis treatment will decrease the genital viral load by at least 1.0 log 10 copies/mL. 2. To determine the prevalence of trichomoniasis among women seen in an HIV clinic in South Africa. Our hypothesis is that the prevalence of trichomoniasis among this high risk group of women reaches or exceeds 10%. 3. To define the vaginal immune inflammatory response to metronidazole treatment among women with HIV and trichomoniasis. Our hypothesis is that the vaginal pro-inflammatory response to trichomoniasis as measured by cytokine concentrations will decrease after treatment. This is a prospective cohort study. HIV-infected women not receiving highly active anti-retroviral therapy (HAART), and with CD4+ cell counts >200/mm 3 presenting to the South African Clinic for care will be offered screening for trichomoniasis. Diagnosis will be made with the use of a rapid immunochromatograohic assay. Those that test positive for T.vaginalis will be given treatment with the standard CDC-recommended regimen for treatment of trichomoniasis. They will receive a single oral dose of 2 grams of metronidazole. Prior to treatment, they will have cervical swabs collected for measurement of genital HIV viral load as well as for measurement of cytokines and chemokines. Vaginal swabs will be collected to assess for the presence of bacterial vaginosis and secretory leukocyte protease inhibitor (SLPI). An R03 grant will be submitted to fund the mucosal immunity portion of the study. Treated subjects will be asked to return for a follow-up visit one month after therapy. Follow-up swabs will be obtained for test-of-cure, viral load measurement, cytokine studies, bacterial vaginosis, and SLPI concentrations. Since the natural history of HIV infection is for viral loads to slowly increase over time, a one-arm trial was chosen for this study. Women will serve as their own controls and all women will receive trichomoniasis treatment because it is standard of care. For this paired sample, estimation was made using mean log-transformed genital viral loads with an alpha=0.05 and beta =0.2. In order to detect a change in viral load of a log change, approximately 57 women need to be enrolled. If appropriate, two-sided paired t-tests will be performed to determine a change from baseline values after treatment.
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