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Edfeldt G, Lajoie J, Röhl M, et al. Regular use of depot medroxyprogesterone acetate causes thinning of the superficial lining and apical distribution of HIV target cells in the human ectocervix. J Infect Dis. 2020;doi: 10.1093/infdis/jiaa514.
Edfeldt, G., Lajoie, J., Röhl, M., Oyugi, J., Åhlberg, A., Khalilzadeh-Binicy, B., Bradley, F., Mack, M., Kimani, J., Omollo, K., Wählby, C., Fowke, K. R., Broliden, K., & Tjernlund, A. (2020). Regular use of depot medroxyprogesterone acetate causes thinning of the superficial lining and apical distribution of HIV target cells in the human ectocervix. The Journal of infectious diseases, . https://doi.org/10.1093/infdis/jiaa514
Edfeldt, Gabriella, et al. "Regular use of depot medroxyprogesterone acetate causes thinning of the superficial lining and apical distribution of HIV target cells in the human ectocervix." The Journal of infectious diseases vol. (2020). doi: https://doi.org/10.1093/infdis/jiaa514
Edfeldt G, Lajoie J, Röhl M, Oyugi J, Åhlberg A, Khalilzadeh-Binicy B, Bradley F, Mack M, Kimani J, Omollo K, Wählby C, Fowke KR, Broliden K, Tjernlund A. Regular use of depot medroxyprogesterone acetate causes thinning of the superficial lining and apical distribution of HIV target cells in the human ectocervix. J Infect Dis. 2020 Aug 11; doi: 10.1093/infdis/jiaa514. Epub 2020 Aug 11. PMID: 32780807.
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J Infect Dis. 2020 Aug 11; doi: 10.1093/infdis/jiaa514. Epub 2020 Aug 11.

Regular use of depot medroxyprogesterone acetate causes thinning of the superficial lining and apical distribution of HIV target cells in the human ectocervix.

The Journal of infectious diseases

Gabriella Edfeldt, Julie Lajoie, Maria Röhl, Julius Oyugi, Alexandra Åhlberg, Behnaz Khalilzadeh-Binicy, Frideborg Bradley, Mathias Mack, Joshua Kimani, Kenneth Omollo, Carolina Wählby, Keith R Fowke, Kristina Broliden, Annelie Tjernlund

Affiliations

  1. Department of Medicine Solna, Division of Infectious Diseases, Karolinska Institutet, Karolinska University Hospital, Center for Molecular Medicine, Stockholm, Sweden.
  2. Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, Manitoba, Canada.
  3. Department of Medical Microbiology, University of Nairobi, Nairobi, Kenya.
  4. Department of Internal Medicine - Nephrology, University Hospital Regensburg, Regensburg, Germany.
  5. Partners for Health and Development in Africa, Nairobi, Kenya.
  6. Department of Information Technology, Uppsala University, Uppsala, Sweden.
  7. SciLifeLab BioImage Informatics Facility, Uppsala, Sweden.
  8. Department of Community Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.

PMID: 32780807 DOI: 10.1093/infdis/jiaa514

Abstract

BACKGROUND: The hormonal contraceptive depot medroxyprogesterone acetate (DMPA) may be associated with an increased risk of acquiring human immunodeficiency virus (HIV). We hypothesize that DMPA use influences the ectocervical tissue architecture and HIV target cell localization.

METHODS: Quantitative image analysis workflows were developed to assess ectocervical tissue samples collected from DMPA users and control subjects not using hormonal contraception.

RESULTS: Compared to controls, the DMPA group exhibited a significantly thinner apical ectocervical epithelial layer and a higher proportion of CD4+CCR5+ cells with a more superficial location. This localization corresponded to an area with a non-intact E-cadherin net structure. CD4+Langerin+ cells were also more superficially located in the DMPA group, while fewer in number compared to the controls. Natural plasma progesterone levels did not correlate with any of these parameters, whereas estradiol levels were positively correlated with E-cadherin expression and a more basal location for HIV target cells of the control group.

CONCLUSIONS: DMPA users have a less robust epithelial layer and a more apical distribution of HIV target cells in the human ectocervix, which could confer a higher risk of HIV infection. Our results highlight the importance of assessing intact genital tissue samples to gain insights into HIV susceptibility factors.

© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.

Keywords: in situ staining; DMPA; HIV; HIV target cells; digital image analysis; epithelial integrity; estradiol; female genital mucosa; hormonal contraception; progesterone

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