Impact of reproductive aging on the vaginal microbiome and soluble immune mediators in women living with and at-risk for HIV infection

Kerry Murphy, Marla J. Keller, Kathryn Anastos, Shada Sinclair, J. Cooper Devlin, Qiuhu Shi, Donald R. Hoover, Brian Starkman, Jamie McGillick, Caroline Mullis, Howard Minkoff, Maria Gloria Dominguez-Bello, Betsy C. Herold

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Background Reproductive aging may impact the vaginal microbiome and genital tract mucosal immune environment and contribute to genital tract health in women living with and at-risk for HIV infection. Methods A cross-sectional study of 102 HIV+ (51 premenopausal, 51 postmenopausal) and 39 HIV-uninfected (HIV-) (20 premenopausal, 19 postmenopausal) women was performed in Bronx and Brooklyn, NY. Cervicovaginal lavage (CVL) was collected for quantification of innate antimicrobial activity against E. coli, HSV-2 and HIV and immune mediators by Luminex and ELISA. Microbiome studies by qPCR and 16S rRNA sequencing were performed on vaginal swabs. Results HIV+ postmenopausal compared to premenopausal participants had lower median E. coli bactericidal activity (41% vs. 62%, p = 0.001), lower median gene copies of Lactobacillus crispatus (p = 0.005) and Lactobacillus iners (p = 0.019), lower proportions of Lactobacillus iners, higher proportions of Gardnerella and Atopobium vaginae and lower levels of human beta defensins (HBD-2, HBD-3) and secretory leukocyte protease inhibitor (SLPI), p<0.001. HSV-2 inhibitory activity was higher in HIV+ postmenopausal compared to premenopausal participants (37% vs. 17%, p = 0.001) and correlated with the proinflammatory molecules interleukin (IL) 6, IL-8, human neutrophil peptide (HNP) 1–3, lactoferrin and fibronectin. Similar trends were observed in HIV- postmenopausal compared to premenopausal participants. HIV inhibitory activity did not differ by reproductive status in the HIV+ participants but was significantly higher in HIV- postmenopausal compared to premenopausal participants and in participants with suppressed plasma viral load, and inversely correlated with gene copies of G. vaginalis and BVAB2. A significant proportion of HIV+ participants on ART exhibited HIV enhancing activity.

Original languageEnglish (US)
Article numbere0216049
JournalPloS one
Volume14
Issue number4
DOIs
StatePublished - Apr 2019

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Murphy, K., Keller, M. J., Anastos, K., Sinclair, S., Cooper Devlin, J., Shi, Q., Hoover, D. R., Starkman, B., McGillick, J., Mullis, C., Minkoff, H., Dominguez-Bello, M. G., & Herold, B. C. (2019). Impact of reproductive aging on the vaginal microbiome and soluble immune mediators in women living with and at-risk for HIV infection. PloS one, 14(4), [e0216049]. https://doi.org/10.1371/journal.pone.0216049