title: The impact of pregnancy on anti-HIV activity of cervicovaginal secretions.
abstract: BACKGROUND
  Mucosal immunity of the female genital tract plays a critical role in defense against sexually transmitted infections like HIV. Pregnancy is associated with both structural and immunologic alterations in the genital mucosa, but the impact of these changes on its ability to suppress HIV infection is unknown. Current epidemiologic data are conflicting as to whether pregnancy increases the risk of HIV acquisition.
  
  
  OBJECTIVE
  The purpose of this study was to define the association between antimicrobial peptides and chemokines in cervicovaginal secretions and in vitro HIV infectivity among pregnant and nonpregnant women.
  
  
  METHODS
  Forty pregnant and 37 nonpregnant women were enrolled in a prospective longitudinal cohort study at a single tertiary care women's hospital in Providence, RI. Cervicovaginal lavage was performed at each study visit. For pregnant women, study visits occurred once per trimester, and there was an optional postpartum visit. For nonpregnant women, study visits occurred across a single cycle that was timed to occur in the proliferative, ovulatory, and secretory phases based on the presumption of a regular menstrual cycle. The impact of cervicovaginal lavage on HIV infectivity was evaluated using a TZM-bl assay and compared between pregnant and nonpregnant women for each visit. The previously validated TZM-bl assay, which uses a luciferase reporting gene to indicate HIV infection of TZM-bl cells, was measured with a luminometer with higher relative light units that indicate greater levels of in vitro HIV infection. Immune mediators were measured with a multiplex bead assay. HIV infectivity and median concentration of each mediator were compared between pregnant and nonpregnant groups with the Wilcoxon rank sum test.
  
  
  RESULTS
  Cervicovaginal fluid from pregnant and nonpregnant women significantly decreased HIV infectivity in both groups compared with positive control (virus only; P<.01), but infectivity was not different between groups (P≥.44). During the second and third trimesters, pregnant women experienced suppression of several cervicovaginal immune mediators that included human beta defensin-2; lactoferrin; macrophage inflammatory protein-3α; regulated on activation, normally T-cell expressed and secreted; and stromal cell-derived factor-1 (all P≤.05). The antimicrobial peptide elafin was significantly correlated with HIV infectivity in both groups across all visits, except at the postpartum visit in the pregnant group (n=16). Secretory leukocyte protease inhibitor also was correlated significantly with infectivity across all visits, but in nonpregnant women only (P≤.03).
  
  
  CONCLUSIONS
  Cervicovaginal secretions from both pregnant and nonpregnant women contain immune mediators that are associated with HIV infectivity in an in vitro assay; however, infectivity was not different between pregnant and nonpregnant groups. If pregnant women are at increased risk for HIV infection, it is unlikely to be mediated by alterations in the effectiveness of these protective secretions.
authors.affiliation: Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, Warren Alpert Medical School of Brown University, Women and Infants Hospital, Providence, RI. Electronic address: bhughes@wihri.org.
authors.forename: Brenna L
authors.initials: BL
authors.lastname: Hughes
authors.affiliation: Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, Warren Alpert Medical School of Brown University, Women and Infants Hospital, Providence, RI; Icahn School of Medicine at Mount Sinai, New York, NY.
authors.forename: Riana
authors.initials: R
authors.lastname: Dutt
authors.affiliation: Department of Obstetrics and Gynecology, Division of Research, Warren Alpert Medical School of Brown University, Women and Infants Hospital, Providence, RI.
authors.forename: Christina
authors.initials: C
authors.lastname: Raker
authors.affiliation: Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, Warren Alpert Medical School of Brown University, Women and Infants Hospital, Providence, RI.
authors.forename: Melody
authors.initials: M
authors.lastname: Barthelemy
authors.affiliation: Department of Physiology and Neurobiology, Geisel School of Medicine at Dartmouth, Lebanon, NH.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Rossoll
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Warren Alpert Medical School of Brown University, Women and Infants Hospital, Providence, RI.
authors.forename: Bharat
authors.initials: B
authors.lastname: Ramratnam
authors.affiliation: Department of Physiology and Neurobiology, Geisel School of Medicine at Dartmouth, Lebanon, NH.
authors.forename: Charles R
authors.initials: CR
authors.lastname: Wira
authors.affiliation: Department of Obstetrics and Gynecology, Department of Medicine, Warren Alpert Medical School of Brown University, Women and Infants Hospital, Providence, RI.
authors.forename: Susan
authors.initials: S
authors.lastname: Cu-Uvin
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002584:Cervix Uteri / Q000276:immunology* / Q000378:metabolism; D054418:Chemokine CCL20 / Q000276:immunology; D054377:Chemokine CXCL12 / Q000276:immunology; D053492:Elafin / Q000276:immunology; D005260:Female; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D018928:Immunity, Mucosal / Q000276:immunology*; D007781:Lactoferrin / Q000276:immunology; D008137:Longitudinal Studies; D011247:Pregnancy / Q000276:immunology*; D011446:Prospective Studies; D053481:Secretory Leukocyte Peptidase Inhibitor; D014621:Vagina / Q000276:immunology* / Q000378:metabolism; D044364:Vaginal Douching; D055815:Young Adult; D023083:beta-Defensins / Q000276:immunology
chemical_list: D054418:Chemokine CCL20; D054377:Chemokine CXCL12; D053492:Elafin; D053481:Secretory Leukocyte Peptidase Inhibitor; D023083:beta-Defensins; D007781:Lactoferrin
keywords: HIV; antimicrobial peptide; cervicovaginal lavage; genital immunity