Skip to main content
Log in

Review on the Biological Mechanisms Associated with Depo-Provera and HIV-1 Risk Acquisition in Women

  • Review Paper
  • Published:
Cell Biochemistry and Biophysics Aims and scope Submit manuscript

Abstract

Women constitute more than 50% out of millions of individuals infected with HIV-1, the major causative agent of acquired immune deficiency syndrome. About 40% of HIV-1 infections have been reported to initiate in the female reproductive tract. However, the mechanisms through which these infections are spread are poorly understood; hence, there is now a major concern in women who use long acting injectable hormonal contraceptives, particularly Depo-Provera and an increase of HIV-1 risk acquisition. Based on literature, Depo-Provera has an affinity for both the glucocorticoid receptor and the progesterone receptor in the female reproductive tract. Therefore, investigating HIV-1 pathogenesis in the female reproductive tract via the glucocorticoid receptor and the progesterone receptor mechanisms in response to the effect of Depo-Provera is of great importance.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Moonsamy, S., Bhakat, S., & Soliman, M. E. S. (2014). Dynamic features of apo and bound HIV-Nef protein reveal the anti-HIV dimerization inhibition mechanism. Journal of Receptors and Signal Transduction, 9893, 1–11.

    Google Scholar 

  2. Sharp, P. M., & Hahn, B. H. (2011). Origins of HIV and the AIDS pandemic. Cold Spring Harbor Perspectives in Medicine, 1, 1–22.

    Article  Google Scholar 

  3. Herrera-Carrillo, E., & Berkhout, B. (2015). Bone marrow gene therapy for HIV/AIDS. Viruses, 7, 3910–3936.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Tomasicchio, M., Avenant, C., Du Toit, A., Ray, R. M., & Hapgood, J. P. (2013). The progestin-only contraceptive medroxyprogesterone acetate, but not norethisterone acetate, enhances HIV-1 Vpr-mediated apoptosis in human CD4+T cells through the glucocorticoid receptor. PLoS ONE, 8(5), 1–15.

    Article  Google Scholar 

  5. Palmisano, L., & Vella, S. (2011). A brief history of antiretroviral therapy of HIV infection: Success and challenges. Annali dell’Istituto Superiore di Sanità, 47(1), 44–48.

    CAS  PubMed  Google Scholar 

  6. Polis, C. B., Phillips, S. J., Curtis, K. M., Westreich, D. J., Steyn, P. S., & Raymond, E., et al. (2014). Hormonal contraceptive methods and risk of HIV acquisition in women: A systematic review of epidemiological evidence. Contraception, 90, 360–390.

    Article  CAS  PubMed  Google Scholar 

  7. Ralph, L. J., McCoy, S. I., Shiu, K., & Padian, N. S. (2015). Hormonal contraceptive use and women’s risk of HIV acquisition: A meta-analysis of observational studies. The Lancet Infectious Diseases, 3099(14), 1–11.

    Google Scholar 

  8. Schindler, A. E., Campagnoli, C., Druckmann, R., Huber, J., Pasqualini, J. R., & Schweppe, K. W., et al. (2003). Classification and pharmacology of progestins. Maturitas, 46, 7–16.

    Article  Google Scholar 

  9. National Institute of Allergy and Infectious Diseases (NIAID) (2005). The HIV life cycle. http://aidsinfo.nih.gov. Accessed 21 June 2016.

  10. Engelman, A., & Cherepanov, P. (2013). The structural biology of HIV-1: Mechanistic and therapeutic insights. Nature Reviews Microbiology, 10(4), 279–290.

    Article  Google Scholar 

  11. Does, A. (2007). HIV and AIDS. Available online at the following website: http://www.learner.org/courses/biology/support/textbook_full.pdf. Accessed 2 June 2017.

  12. Mostad, S. B., Overbaugh, J., DeVange, D. M., Welch, M. J., Chohan, B., & Mandaliya, K., et al. (1997). Hormonal contraception, vitamin a deficiency, and other risk factors for shedding of HIV-1 infected cells from the cervix and vagina. Lancet, 350, 922–927.

    Article  CAS  PubMed  Google Scholar 

  13. Mmbaga, E. J. (2013). HIV prevalence and associated risk factors: Analysis of change over time in mainland Tanzania. DHS working papers 85, 1–38.

  14. Bruland, T. (2003). Studies of early retrovi rus-host interactions. Norwegian University of Science and Technology. Det medisinske fakullet.

  15. Nguyen, P. V., Kafka, J. K., Ferreira, V. H., Roth, K., & Kaushic, C. (2014). Innate and adaptive immune responses in male and female reproductive tracts in homeostasis and following HIV infection. Cellular & Molecular Immunology, 11, 410–427.

    Article  CAS  Google Scholar 

  16. Hills-Nieminen, C., Foisy, M., & Tseng, A. (2015). Interaction between antiretrovirals (ARVs) and hormonal contraceptives. http://www.hivclinic.ca. Accessed 21 June 2016.

  17. UNAIDS (2013). Access to antiretroviral therapy in Africa: Status report on progress towards the 2015 targets. http://www.unaids.org/sites/default/files/media_asset/20131219_AccessARTAfricaStatusReportProgresstowards2015Targets. Accessed 21 June 2016.

  18. Lundgren, J. D., Babiker, A. G., Gordin, F., Emery, S., Grund, B., & Sharma, S., et al. (2015). Initiation of antiretroviral therapy in early asympyomatic HIV infection. The New England Journal of Medicine, 373(9), 795–807.

    Article  CAS  PubMed  Google Scholar 

  19. Hicks, C., & Gulick, R. M. (2009). Raltegravir: The first HIV type 1 integrase inhibitor. Clinical Infectious Diseases, 48, 931–939.

    Article  CAS  PubMed  Google Scholar 

  20. Watts, D. H., Park, J. G., Cohn, S. E., Yu, S., Hitti, J., & Stek, A., et al. (2008). Safety and tolerability of depot medroxyprogesterone acetate among HIV-infected women on antiretroviral therapy: ACTG A5093. Contraception, 77, 84–90.

    Article  CAS  PubMed  Google Scholar 

  21. Bonny, A. E., Ziegler, J., Harvey, R., Debanne, S. M., Sesic, M., & Cromer, B. A. (2006). Weight gain in obese and nonobese adolescent girls initiating depot medroxyprogesterone, oral contraceptive pills, or no hormonal contraceptive method. Archives of Pediatrics & Adolescent Medicine, 160, 40–45.

    Article  Google Scholar 

  22. McKay, L. I., & Cidlowski, J. A. (1999). Molecular control of immune/inflammatory responses: Interactions between nuclear factor-kB and steroid receptor-signaling pathways. Endocrine Reviews, 20(4), 435–459.

    CAS  PubMed  Google Scholar 

  23. Bledsoe, R. K., Montana, V. G., Stanley, T. B., Delves, C. J., Apolito, C. J., & McKee, D. D., et al. (2002). Crystal structure of the glucocorticoid receptor ligand binding domain reveals a novel mode of receptor dimerization and coactivator recognition. Cell, 110, 93–105.

    Article  CAS  PubMed  Google Scholar 

  24. Africander, D., Verhoog, N., & Hapgood, J. P. (2011). Molecular mechanisms of steroid receptor-mediated actions by synthetic progestins used in HRT and contraception. Steroids, 76, 636–652.

    Article  CAS  PubMed  Google Scholar 

  25. Aranda, A., & Pascual, A. (2001). Nuclear hormone receptors and gene expression. Physiological Reviews, 81, 1269–1304.

    Article  CAS  PubMed  Google Scholar 

  26. De Bosscher, K., Van Craenenbroeck, K., Meijer, O. C., & Haegeman, G. (2008). Selective transrepression versus transactivation mechanisms by glucocorticoid receptor modulators in stress and immune systems. European Journal of Pharmacology, 583, 290–302.

    Article  PubMed  Google Scholar 

  27. Sedwick, C. (2014). Wanted: A new model for glucocorticoid receptor transactivation and transrepression. PLoS Biology, 12(3), 1–2.

    Article  Google Scholar 

  28. Zhong, H., Voll, R. E., & Ghosh, S. (1998). Phosphorylation of NF-kappa B p65 by PKA stimulates transcriptional activity by promoting a novel bivalent interaction with the coactivator CBP/p300. Molecular Cell, 1, 661–671.

    Article  CAS  PubMed  Google Scholar 

  29. Oeckinghaus, A., & Ghosh, S. (2009). The NF-kappaB family of transcription factors and its regulation. Cold Spring Harbor Perspectives in Biology, 1, 1–14.

    Article  Google Scholar 

  30. Barnes, P. J., Adcock, I. M., & Ito, K. (2005). Histone acetylation and deacetylation: Importance in inflammatory lung diseases. The European Respiratory Journal, 25(3), 552–563.

    Article  CAS  PubMed  Google Scholar 

  31. Louw-du Toit, R., Hapgood, J. P., & Africander, D. (2014). Medroxyprogesterone acetate differentially regulates interleukin (IL)-12 and IL-10 in a human ectocervical epithelial cell line in a glucocorticoid receptor (GR)-dependent manner. The Journal of Biological Chemistry, 289, 31136–31149.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Felzien, L. K., Woffendin, C., Hottiger, M. O., Subbramanian, R. A., Cohen, E. A., & Nabel, G. J. (1998). HIV transcriptional activation by the accessory protein, VPR, is mediated by the p300 co-activator. Proceedings of the National Academy of Sciences USA, 95, 5281–5286.

    Article  CAS  Google Scholar 

  33. Guenzel, C., Herate, C., & Benichou, S. (2014). HIV-1 Vpr-a still “enigmatic multitasker”. Frontiers in Microbiology, 5, 1–13.

    Article  Google Scholar 

  34. Wu, Y., Zhou, X., Barnes, C. O., Delucia, M., Cohen, A. E., Gronenborn, A. M., Ahn, J., & Calero, G. (2016). The DDB1-DCAF1-Vpr-UNG2 crystal structure reveals how HIV-1 Vpr steers human UNG2 toward destruction. Nature Structural & Molecular Biology, 23, 933–940.

    Article  CAS  Google Scholar 

  35. Zahoor, M. A., Xue, G., Sato, H., Murakami, T., Takeshima, S. N., & Aida, Y. (2014). HIV-1 Vpr induces interferon-stimulated genes in human monocyte-derived macrophages. PLoS ONE, 9(8), 1–13.

    Article  Google Scholar 

  36. Williams S. P., & Sigler P. B. (1998) Atomic structure of progesterone complexed with its receptor. Nature, 393, 392–396.

    Article  CAS  PubMed  Google Scholar 

  37. Irwin J. J., & Shoichet B. K. (2005) Zinc- A free database of commercially available compounds for Virtual Screening. Journal of Chemical Information and Modeling, 45(1), 177–182.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Trott O., & Olson A. J. (2010) AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization and multithreading. Journal of Computational Chemistry, 31(2), 455–461.

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors would like to acknowledge the University of KwaZulu-Natal, College of Health Sciences for funding, and the Centre for High Performance Computing for computational resources.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Mahmoud E. S. Soliman.

Ethics declarations

Conflict of Interest

The authors declare that they have no competing interests.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Takalani, F., Mhlongo, N.N., Moonsamy, S. et al. Review on the Biological Mechanisms Associated with Depo-Provera and HIV-1 Risk Acquisition in Women. Cell Biochem Biophys 76, 73–82 (2018). https://doi.org/10.1007/s12013-017-0806-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12013-017-0806-5

Keywords

Navigation