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Ex Vivo Infection of Human Lymphoid Tissue and Female Genital Mucosa with Human Immunodeficiency Virus 1 and Histoculture
Published on: October 12, 2018
Cervicovaginal Secretions in Young Women With Bacterial Vaginosis Enhance HIV Infection
Marla J Keller1, Tao Wang2, Kerry Murphy1,3
1Department of Medicine.
Background:
Bacterial vaginosis (BV) is a major health problem associated with increased HIV risk. To explore underlying mechanisms, we assessed the cervicovaginal mucosal immune environment before and after metronidazole treatment in women with BV and healthy controls.
Methods:
Women with BV diagnosed clinically by Amsel criteria were treated with oral or intravaginal metronidazole. Vaginal swabs and cervicovaginal lavage (CVL) were obtained at enrollment and approximately 2 and 4 weeks later for assessment of immune mediators, antiviral activity, and 16-second rRNA gene sequencing. Healthy controls had sampling at enrollment and 4 weeks.
Results:
Vaginal pH, Nugent score, Shannon diversity index, and vaginal community state types differed significantly at enrollment between women with clinical BV (n = 19) and controls (n = 13, P < .001). BV cases had significantly higher CVL IL-1α and TNF-α but lower IgG at enrollment as compared with controls, which improved following treatment. Similar results were observed if participants with discordant molecular results (n = 3) were excluded. Most notably, CVL from BV cases enhanced, whereas control CVL inhibited, HIV infection of cells relative to buffer (mean ± SD, 138.4% ± 109.8% vs 30.9% ± 37.9%; P = .001). There was a transient reduction in HIV enhancement following treatment, which was not sustained. Enhancement correlated with community state types and markers of dysbiosis. Specifically, decreases in lactobacilli and increases in Prevotella, Dialister micraerophilus, and Peptoniphilus lacrimalis were associated with enhancement.
Conclusions:
These findings provide a potential mechanistic link that may contribute to the increased risk of HIV in association with BV, and they highlight the importance of early diagnosis and improved treatments.
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