title: 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-1BaLamong 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.affiliation: 1 CONRAD Clinical Research Center , Eastern Virginia Medical School, Norfolk, Virginia.
authors.forename: Andrea Ries
authors.initials: AR
authors.lastname: Thurman
authors.affiliation: 1 CONRAD Clinical Research Center , Eastern Virginia Medical School, Norfolk, Virginia.
authors.forename: Nazita
authors.initials: N
authors.lastname: Yousefieh
authors.affiliation: 1 CONRAD Clinical Research Center , Eastern Virginia Medical School, Norfolk, Virginia.
authors.forename: Neelima
authors.initials: N
authors.lastname: Chandra
authors.affiliation: 1 CONRAD Clinical Research Center , Eastern Virginia Medical School, Norfolk, Virginia.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kimble
authors.affiliation: 2 V.A. Medical Center , White River Junction, Vermont.|3 Geisel School of Medicine at Dartmouth , Hanover, New Hampshire.
authors.forename: Susana
authors.initials: S
authors.lastname: Asin
authors.affiliation: 2 V.A. Medical Center , White River Junction, Vermont.|3 Geisel School of Medicine at Dartmouth , Hanover, New Hampshire.
authors.forename: Christiane
authors.initials: C
authors.lastname: Rollenhagen
authors.affiliation: 1 CONRAD Clinical Research Center , Eastern Virginia Medical School, Norfolk, Virginia.
authors.forename: Sharon M
authors.initials: SM
authors.lastname: Anderson
authors.affiliation: 4 Albert Einstein College of Medicine , Bronx, New York.
authors.forename: Betsy C
authors.initials: BC
authors.lastname: Herold
authors.affiliation: 4 Albert Einstein College of Medicine , Bronx, New York.
authors.forename: Jamie L
authors.initials: JL
authors.lastname: Freiermuth
authors.affiliation: 4 Albert Einstein College of Medicine , Bronx, New York.
authors.forename: Brian S
authors.initials: BS
authors.lastname: Starkman
authors.affiliation: 4 Albert Einstein College of Medicine , Bronx, New York.
authors.forename: Pedro M M
authors.initials: PMM
authors.lastname: Mesquita
authors.affiliation: 5 Alpha StatConsult , Damascus, Maryland.
authors.forename: Nicola
authors.initials: N
authors.lastname: Richardson-Harman
authors.affiliation: 6 Center for Health Analytics and Discovery , Eastern Virginia Medical School, Norfolk, Virginia.
authors.forename: Tina
authors.initials: T
authors.lastname: Cunningham
authors.affiliation: 7 Magee-Womens Research Institute , Pittsburgh, Pennsylvania.|8 University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania.
authors.forename: Sharon
authors.initials: S
authors.lastname: Hillier
authors.affiliation: 7 Magee-Womens Research Institute , Pittsburgh, Pennsylvania.
authors.forename: Lorna
authors.initials: L
authors.lastname: Rabe
authors.affiliation: 1 CONRAD Clinical Research Center , Eastern Virginia Medical School, Norfolk, Virginia.
authors.forename: Jill L
authors.initials: JL
authors.lastname: Schwartz
authors.affiliation: 1 CONRAD Clinical Research Center , Eastern Virginia Medical School, Norfolk, Virginia.
authors.forename: Gustavo F
authors.initials: GF
authors.lastname: Doncel
mesh_terms: D000282:Administration, Intravaginal; D000328:Adult; D000368:Aged; D002584:Cervix Uteri / Q000821:virology; D004198:Disease Susceptibility; D004958:Estradiol / Q000008:administration & dosage*; D004967:Estrogens / Q000008:administration & dosage*; D005260:Female; D006678:HIV / Q000254:growth & development / Q000276:immunology*; D016655:HIV Core Protein p24 / Q000032:analysis; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D018928:Immunity, Mucosal; D008875:Middle Aged
chemical_list: D004967:Estrogens; D016655:HIV Core Protein p24; D004958:Estradiol
keywords: HIV; cervicovaginal; hormones; menopause; mucosal