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  • Title: HIV-1 infection associated with abnormal vaginal flora morphology and bacterial vaginosis.
    Author: Sewankambo N, Gray RH, Wawer MJ, Paxton L, McNaim D, Wabwire-Mangen F, Serwadda D, Li C, Kiwanuka N, Hillier SL, Rabe L, Gaydos CA, Quinn TC, Konde-Lule J.
    Journal: Lancet; 1997 Aug 23; 350(9077):546-50. PubMed ID: 9284776.
    Abstract:
    BACKGROUND: In-vitro research has suggested that bacterial vaginosis may increase the survival of HIV-1 in the genital tract. Therefore, we investigated the association of HIV-1 infection with vaginal flora abnormalities, including bacterial vaginosis and depletion of lactobacilli, after adjustment for sexual activity and the presence of other sexually transmitted diseases (STDs). METHODS: During the initial survey round of our community-based trial of STD control for HIV-1 prevention in rural Rakai District, southwestern Uganda, we selected 4718 women aged 15-59 years. They provided interview information, blood for HIV-1 and syphilis serology, urine for detection of Chlamydia trachomatis and Neisseria gonorrhoeae, and two self-administered vaginal swabs for culture of Trichomonas vaginalis and gram-stain detection of vaginal flora, classified by standardised, quantitative, morphological scoring. Scores 0-3 were normal vaginal flora (predominant lactobacilli). Higher scores suggested replacement of lactobacilli by gram-negative, anaerobic microorganisms (4-6 intermediate; 7-8 and 9-10 moderate and severe bacterial vaginosis). FINDINGS: HIV-1 frequency was 14.2% among women with normal vaginal flora and 26.7% among those with severe bacterial vaginosis (p < 0.0001). We found an association between bacterial vaginosis and increased HIV-1 infection among younger women, but not among women older than 40 years; the association could not be explained by differences in sexual activity or concurrent infection with other STDs. The frequency of bacterial vaginosis was similar among HIV-1-infected women with symptoms (55.0%) and without symptoms (55.7%). The adjusted odds ratio of HIV-1 infection associated with any vaginal flora abnormality (scores 4-10) was 1.52 (95% CI 1.22-1.90), for moderate bacterial vaginosis (scores 7-8) it was 1.50 (1.18-1.89), and for severe bacterial vaginosis (scores 9-10) it was 2.08 (1.48-2.94). INTERPRETATION: This cross-sectional study cannot show whether disturbed vaginal flora increases susceptibility to HIV-1 infection. Nevertheless, the increased frequency of HIV-1 associated with abnormal flora among younger women, for whom HIV-1 acquisition is likely to be recent, but not among older women, in whom HIV-1 is likely to have been acquired earlier, suggests that loss of lactobacilli or presence of bacterial vaginosis may increase susceptibility to HIV-1 acquisition. If this inference is correct, control of bacterial vaginosis could reduce HIV-1 transmission. A study of 4718 women 15-49 years old in southwestern Uganda's Rakai district suggests that the loss of lactobacilli and the presence of bacterial vaginosis may increase susceptibility to HIV-1. These women were part of an ongoing community-based trial of sexually transmitted disease (STD) control as a strategy for AIDS prevention. The rate of HIV-1 infection among these women was 19.5%. Moderate bacterial vaginosis was detected in 44.5% of women, while 6.4% had severe bacterial vaginosis. STD rates were 10.2% for active or recent syphilis, 22.4% for trichomonas, 2.4% for gonorrhea, and 3.6% for chlamydia. The HIV rate was lowest (14.2%) among women with normal bacterial flora and highest (26.7%) among those with severe bacterial vaginosis. The HIV-abnormal flora association was higher in younger women, for whom HIV acquisition is likely to be recent, than in older women. In multiple logistic regression analyses adjusted for age, number of sexual partners, trichomonas, and syphilis, the odds ratio (OR) for HIV-1 infection associated with any abnormal vaginal flora was 1.52 (95% confidence interval [CI], 1.22-1.90) and with all bacterial vaginosis was 1.56 (95% CI, 1.24-1.97). These adjusted ORs were 1.50 (95% CI, 1.18-1.89) for moderate and 2.08 (95% CI, 1.48-2.94) for severe bacterial vaginosis. A cross-sectional study cannot ascertain whether the abnormalities in vaginal flora occurred before or after HIV seroconversion. However, the significantly increased proportion of HIV-infected women with depleted or absent vaginal lactobacilli is consistent with in vitro studies showing that hydrogen peroxidase-producing lactobacilli in vaginal flora inhibit HIV-1 viral replication. If the ongoing prospective study suggests a causal association with HIV, treatment of abnormal flora or bacterial vaginosis with inexpensive, effective drugs such as metronidazole may be indicated.
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