Marla J Keller1, Ashley Huber2,3, Lilia Espinoza1, Myrna G Serrano4,5, Hardik I Parikh6, Gregory A Buck4,5,7, Jeremy A Gold1,8, Yiqun Wu9,10, Tao Wang9, Betsy C Herold2,11. 1. Departments of Medicine, Albert Einstein College of Medicine, Bronx, New York. 2. Departments of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York. 3. Present Affiliation: Department of Obstetrics, Gynecology and Reproductive Medicine, Stony Brook University School of Medicine, Stony Brook, New York. 4. Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond. 5. Center for Microbiome Engineering and Data Analysis, Virginia Commonwealth University, Richmond. 6. School of Medicine Research Computing, University of Virginia, Charlottesville. 7. Computer Science Department, Virginia Commonwealth University, Richmond. 8. Present Affiliation: Department of Medicine, Columbia University, College of Physicians and Surgeons, New York, New York. 9. Departments of Epidemiology and Population Health, Bronx, New York. 10. Present Affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China. 11. Department of Pediatrics, Albert Einstein College of Medicine and Children's Hospital at Montefiore, Bronx, New York.
Abstract
BACKGROUND: Mechanisms linking herpes simplex virus type 2 (HSV-2) with human immunodeficiency virus (HIV) are not fully defined. We tested the hypothesis that HSV-2 and HIV dual infection is associated with cervicovaginal inflammation and/or vaginal dysbiosis. METHODS: Genital tract samples were obtained weekly over a 12-week period from 30 women seropositive (+) for HIV and HSV-2 and 15 women each who were seropositive for one or seronegative (-) for both viruses. Immune mediators, antimicrobial activity, and microbial composition and diversity were compared. RESULTS: Significant differences in the concentrations of interferon-γ (P = .002), tumor necrosis factor-α (P = .03), human beta defensin 1 (P = .001), secretory leukocyte protease inhibitor (P = .01), and lysozyme (P = .03) were observed across the 4 groups (Kruskal-Wallis). There were also significant differences in vaginal microbial alpha diversity (Simpson index) (P = .0046). Specifically, when comparing HIV-1+/HSV-2+ to HIV-1-/HSV-2- women, a decrease in Lactobacillus crispatus and increase in diverse anaerobes was observed. The number of genital HSV outbreaks was greater in HIV+ versus HIV- women (39 versus 12) (P = .04), but there were no significant differences when comparing outbreak to non-outbreak visits. CONCLUSIONS: Increased microbial diversity and cervicovaginal inflammation in HIV and HSV-2 dually infected women may adversely impact genital health and, in the absence of antiretroviral therapy, facilitate HIV shedding.
BACKGROUND: Mechanisms linking herpes simplex virus type 2 (HSV-2) with human immunodeficiency virus (HIV) are not fully defined. We tested the hypothesis that HSV-2 and HIV dual infection is associated with cervicovaginal inflammation and/or vaginal dysbiosis. METHODS: Genital tract samples were obtained weekly over a 12-week period from 30 women seropositive (+) for HIV and HSV-2 and 15 women each who were seropositive for one or seronegative (-) for both viruses. Immune mediators, antimicrobial activity, and microbial composition and diversity were compared. RESULTS: Significant differences in the concentrations of interferon-γ (P = .002), tumor necrosis factor-α (P = .03), humanbeta defensin 1 (P = .001), secretory leukocyte protease inhibitor (P = .01), and lysozyme (P = .03) were observed across the 4 groups (Kruskal-Wallis). There were also significant differences in vaginal microbial alpha diversity (Simpson index) (P = .0046). Specifically, when comparing HIV-1+/HSV-2+ to HIV-1-/HSV-2- women, a decrease in Lactobacillus crispatus and increase in diverse anaerobes was observed. The number of genital HSV outbreaks was greater in HIV+ versus HIV- women (39 versus 12) (P = .04), but there were no significant differences when comparing outbreak to non-outbreak visits. CONCLUSIONS: Increased microbial diversity and cervicovaginal inflammation in HIV and HSV-2 dually infected women may adversely impact genital health and, in the absence of antiretroviral therapy, facilitate HIV shedding.
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