Bacterial vaginosis (BV) is a common condition in women characterized by an overgrowth of a mixture of anaerobic and other bacteria, typically including Gardnerella vaginalis and Mycoplasmas. However, the flora that constitutes BV can be highly variable. Women with BV have a higher incidence of HIV infection suggesting that BV increases susceptibility to HIV infection. One expansion for increased susceptibility is that BV organisms replace lactobacilli that produce virucidal substances. However, it is also possible that BV affects HIV replication in the genital tract by either increasing the susceptibility of cells to HIV infection or by stimulating cells to produce virus. A recent study showed that HIV RNA was detected more frequently in cervicovaginal lavage (CVL) fluid from women with BV showed that HIV RNA was detected more frequently in cervico vaginal lavage (CVL) fluid from women with BV than those without. Previous work by our group showed that some BV-associated organisms (e.g. G vaginalis and M. hominis) stimulated HIV expression by infected cells while others (U. Urealyticum and lactobacilli) did not). We hypothesize that colonization by certain BV-associated bacteria increases genital tract virus load (VL). To test this in aim 1 we will obtain CVL samples from a cross-section of HIV+ women with and without BV. The numbers of four specific bacteria, G. vaginalis, M. hominis, Mobiluncus and Lactobacillus will be determined by PCR and compared with the genital tract VL.
In aim 2, women with BV will be treated and the effect on genital tract VL and bacterial will be determined. A significant association between HIV and a specific organism, or reduction due to treatment, would indicate that colonization with that organism influences genital tract VL, provide an explanation for how BV increases susceptibility to HIV infection and point strategies for reducing transmission. Earlier we found that expression of a genital tract factor that induces HIV replication (HIF) was significantly associated with BV. We also hypothesize that treatment of BV will decrease HIF expression and will test this aim in aim 3 to determine a cause and effect relationship between BV and HIF. Finally, in aim 4 the effect of BV, HIF and BV-bacteria on induction of specific genital tract immune responses in vaccinated seronegative women will be determined.
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