The Effect of Hormonal Contraception on Cervicovaginal Mucosal End Points Associated with HIV Acquisition

Andrea Thurman, Neelima Chandra, Jill L. Schwartz, Vivian Brache, Beatrice A. Chen, Susana Asin, Christiane Rollenhagen, Betsy Herold, Raina N. Fichorova, Sharon L. Hillier, Debra H. Weiner, Christine Mauck, Gustavo F. Doncel

Research output: Contribution to journalArticle

Abstract

Reproductive age women may choose to concurrently use topical antiretrovirals and hormonal contraceptives (HCs) to simultaneously prevent HIV-1 infection and unintended/mistimed pregnancy. There are conflicting data on the effect of HCs on mucosal susceptibility to HIV-1. The objective of this study was to evaluate cervicovaginal (CV) mucosal data from healthy women before and after initiation of either oral contraceptive pills (OCPs) or depot medroxyprogesterone acetate (DMPA) injection. CONRAD A10-114 was a prospective, open-label, parallel cohort study. We enrolled 74 women and 62 completed the visits (32 and 30 who selected OCPs and DMPA, respectively). Participants provided CV lavage, vaginal biopsies, and CV swabs at baseline in the luteal phase and then ∼6 weeks after initiating HCs. After contraceptive initiation, there were significant increases in vaginal immune cell density among both DMPA and OCP users. Changes for OCP users were concentrated in the subepithelial lamina propria, whereas for DMPA users, they were distributed throughout the vaginal tissue, including the epithelium (CD45+, CD3+, CD4+, and CD1a+). Contraceptive use altered concentrations of soluble CV inflammatory and immune mediators, with significant reductions in some proinflammatory cytokines and secretory leukoprotease inhibitor. Compared with baseline, p24 antigen production after ex vivo HIV-1 infection of vaginal biopsies doubled after DMPA use, but all p-values were >.05. HIV-1 replication was significantly higher in DMPA-exposed tissues compared with those from the OCP group at the end of the tissue culture (p = .01). Although not statistically significant, median in vitro inhibition of HIV-1 by CV fluid (innate antiviral activity), was reduced by ∼50% with HCs (p > .21). Exposure to exogenous contraceptive hormones significantly increased vaginal immune cells and reduced CV proinflammatory cytokines and antimicrobial peptides. DMPA users showed higher susceptibility to HIV-1 ex vivo infection.

Original languageEnglish (US)
Pages (from-to)853-864
Number of pages12
JournalAIDS Research and Human Retroviruses
Volume35
Issue number9
DOIs
StatePublished - Sep 1 2019

Fingerprint

Medroxyprogesterone Acetate
Contraceptive Agents
Contraception
HIV-1
Oral Contraceptives
HIV
HIV Infections
Vaginal Douching
Secretory Leukocyte Peptidase Inhibitor
Cytokines
Biopsy
Luteal Phase
antineoplaston A10
Antiviral Agents
Mucous Membrane
Cohort Studies
Epithelium
Cell Count
Hormones
Antigens

Keywords

  • contraceptives
  • HIV
  • inflammation
  • microbicides
  • mucosal safety

ASJC Scopus subject areas

  • Immunology
  • Virology
  • Infectious Diseases

Cite this

Thurman, A., Chandra, N., Schwartz, J. L., Brache, V., Chen, B. A., Asin, S., ... Doncel, G. F. (2019). The Effect of Hormonal Contraception on Cervicovaginal Mucosal End Points Associated with HIV Acquisition. AIDS Research and Human Retroviruses, 35(9), 853-864. https://doi.org/10.1089/aid.2018.0298

The Effect of Hormonal Contraception on Cervicovaginal Mucosal End Points Associated with HIV Acquisition. / Thurman, Andrea; Chandra, Neelima; Schwartz, Jill L.; Brache, Vivian; Chen, Beatrice A.; Asin, Susana; Rollenhagen, Christiane; Herold, Betsy; Fichorova, Raina N.; Hillier, Sharon L.; Weiner, Debra H.; Mauck, Christine; Doncel, Gustavo F.

In: AIDS Research and Human Retroviruses, Vol. 35, No. 9, 01.09.2019, p. 853-864.

Research output: Contribution to journalArticle

Thurman, A, Chandra, N, Schwartz, JL, Brache, V, Chen, BA, Asin, S, Rollenhagen, C, Herold, B, Fichorova, RN, Hillier, SL, Weiner, DH, Mauck, C & Doncel, GF 2019, 'The Effect of Hormonal Contraception on Cervicovaginal Mucosal End Points Associated with HIV Acquisition', AIDS Research and Human Retroviruses, vol. 35, no. 9, pp. 853-864. https://doi.org/10.1089/aid.2018.0298
Thurman, Andrea ; Chandra, Neelima ; Schwartz, Jill L. ; Brache, Vivian ; Chen, Beatrice A. ; Asin, Susana ; Rollenhagen, Christiane ; Herold, Betsy ; Fichorova, Raina N. ; Hillier, Sharon L. ; Weiner, Debra H. ; Mauck, Christine ; Doncel, Gustavo F. / The Effect of Hormonal Contraception on Cervicovaginal Mucosal End Points Associated with HIV Acquisition. In: AIDS Research and Human Retroviruses. 2019 ; Vol. 35, No. 9. pp. 853-864.
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