Impact of Herpes Simplex Virus Type 2 and Human Immunodeficiency Virus Dual Infection on Female Genital Tract Mucosal Immunity and the Vaginal Microbiome

J Infect Dis. 2019 Jul 31;220(5):852-861. doi: 10.1093/infdis/jiz203.

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.

Keywords: herpes simplex virus; human immunodeficiency virus; microbiome; mucosal immunity; vaginal dysbiosis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Anti-Infective Agents / pharmacology
  • Coinfection / virology
  • Dysbiosis
  • Female
  • Genitalia, Female / microbiology*
  • HIV Infections / complications*
  • Herpes Genitalis / epidemiology
  • Herpes Genitalis / immunology*
  • Herpes Genitalis / virology
  • Herpesvirus 2, Human / immunology*
  • Humans
  • Immunity, Mucosal / immunology*
  • Interferon-gamma
  • Lactobacillus
  • Microbiota / physiology*
  • Middle Aged
  • Muramidase
  • Secretory Leukocyte Peptidase Inhibitor
  • Tumor Necrosis Factor-alpha
  • Vagina / microbiology*
  • Vagina / virology
  • Virus Shedding
  • beta-Defensins

Substances

  • Anti-Infective Agents
  • SLPI protein, human
  • Secretory Leukocyte Peptidase Inhibitor
  • Tumor Necrosis Factor-alpha
  • beta-Defensins
  • Interferon-gamma
  • Muramidase