Comparison of Mucosal Markers of Human Immunodeficiency Virus Susceptibility in Healthy Premenopausal Versus Postmenopausal Women.

Abstract

The objective of this study was to characterize cervicovaginal (CV) mucosal factors modulating susceptibility to human immunodeficiency virus (HIV) acquisition in healthy premenopausal (PRE) and postmenopausal (POST) women before and after treatment with estradiol (E2). We compared CV mucosal epithelial histology and immune cells, vaginal microbiota, antimicrobial activity of and soluble mucosal protein concentrations in the CV fluid lavage (CVL), and p24 antigen production after ex vivo infection of ectocervical tissues with HIV-1BaL among PRE women (n = 20) in the follicular and luteal phases of the menstrual cycle and POST women (n = 17) at baseline and after ∼1 month of treatment with 0.01% vaginal E2 cream. Compared to PRE women, we measured higher levels of p24 antigen after ex vivo infection in tissues from POST women. POST women had a significantly thinner vaginal epithelium with decreased tight junction proteins and a higher density of mucosal immune T cells and lower levels of CD1a antigen-presenting cells, antimicrobial peptides, and inflammatory cytokines in the CVL (p values <.05). POST women had higher vaginal pH and lower vaginal Lactobacilli (p values <.05) than PRE women. After vaginal E2 therapy, CV endpoints and ex vivo HIV replication in POST tissues were similar to those observed in PRE tissues. The CV mucosa in POST women is thinned and compromised, with increased HIV-target immune cells and decreased antimicrobial factors, being more susceptible to HIV infection. After POST women receive topical E2 treatment, mucosal endpoints are similar to PRE levels.

• Authors: Andrea Ries Thurman, Nazita Yousefieh, Neelima Chandra, Thomas Kimble, Susana Asin, Christiane Rollenhagen, Sharon M Anderson, Betsy C Herold, Jamie L Freiermuth, Brian S Starkman, Pedro M M Mesquita, Nicola Richardson-Harman, Tina Cunningham, Sharon Hillier, Lorna Rabe, Jill L Schwartz, Gustavo F Doncel
• Journal: AIDS research and human retroviruses (AIDS Res Hum Retroviruses) Vol. 33 Issue 8 Pg. 807-819 (08 2017) ISSN: 1931-8405 [Electronic] United States
• PMID: 28398069 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Estrogens
• HIV Core Protein p24
• Estradiol

Topics

• Administration, Intravaginal
• Adult
• Aged
• Cervix Uteri (virology)
• Disease Susceptibility
• Estradiol (administration & dosage)
• Estrogens (administration & dosage)
• Female
• HIV (growth & development, immunology)
• HIV Core Protein p24 (analysis)
• HIV Infections (immunology)
• Humans
• Immunity, Mucosal
• Middle Aged