PREVENTION OF HIV SHEDDING IN WOMEN--TRIAL OF VITAMIN A

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DESCRIPTION: Despite encouraging advances in treating and preventing HIV infection in North America and Western Europe, the epidemic continues to spread rapidly in many parts of the world. The need for new strategies to prevent heterosexual and vertical transmission remains pressing. HIV-1 can be detected in genital tract secretions of infected individuals, and there is epidemiologic evidence that this is a marker of enhanced infectivity. Recent studies of correlates of genital tract shedding of HIV-1 DNA in infected women have found that lower serum concentrations of vitamin A were strongly associated with detection of HIV-1 DNA in vaginal secretions. Vitamin a deficiency leads to characteristic pathological changes in mucosal epithelium, including the vagina, and is correlated with immune dysfunction in both HIV-1 infected and uninfected individuals. In addition, maternal vitamin A deficiency has been associated with significantly increased risk of vertical HIV-1 transmission. We propose a randomized double-blind placebo-controlled trial to assess the effect of vitamin A supplementation on the prevalence and quantity of HIV-1 DNA and RNA in cervical and vaginal secretions in 400 HIV-infected nonpregnant women in Mombasa, Kenya. Participants will be randomized to receive six weeks of daily dosage of either 10,000 IU vitamin A or placebo. Cervical and vaginal swabs will be obtained at enrollment and at six weeks for detection and quantification of HIV-1 DNA and RNA. In addition, venous blood will be obtained at the two time points for quantification of plasma HIV-1 RNA, CD4 lymphocyte count, and serum vitamin A levels. Normalization of vitamin A status in supplemented HIV-1 infected women may improve genital mucosal integrity and immunity, thereby potentially decreasing the infectiousness of these women. In a pilot study, we found that vitamin A supplementation resulted in a two-fold decrease in vaginal HIV-1 DNA detection. If this preliminary result is confirmed in a full-scale clinical trial, vitamin A supplementation may offer a simple inexpensive intervention to decrease heterosexual and vertical transmission of HIV-1 in the developing world.