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Interactions Between Hormonal Contraception and Anti-Retroviral Therapy: an Updated Review

  • Family Planning (A Burke, Section Editor)
  • Published:
Current Obstetrics and Gynecology Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Hormonal contraception provides women living with HIV the ability to control their fertility and avoid pregnancy-related morbidity. Due to shared metabolic pathways, there has been concern over drug-drug interactions between hormonal contraception and anti-retroviral therapy, which may affect the drugs’ safety and efficacy. This article aims to provide an updated review of the most recent data around hormonal contraceptives and anti-retroviral therapy.

Recent Findings

Prior data have suggested possible pharmacologic interactions between certain hormonal contraceptives and anti-retroviral therapy. The most significant interactions implicated include those between progestin-based contraceptive implants and efavirenz as well as between combined hormonal contraceptives and protease inhibitors. Most past studies, however, feature small sample sizes with few clinical outcomes reported.

Summary

Recent data since 2017 have largely affirmed prior studies on this topic, showing possible pharmacokinetic relationships between certain contraceptives and anti-retrovirals. Notably, while the effectiveness of progestin-based contraceptives, specifically the implant, appears reduced with efavirenz use, the overall effectiveness may remain higher than most other contraceptive methods. Larger studies are needed to provide further guidance before contraceptive-prescribing recommendations can be changed.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. UNAIDS. Global HIV & AIDS Statistics 2019 Fact sheet. UN AIDS 2019. http://www.unaids.org/en/resources/fact-sheet. Accessed 02 Jan 2020.

  2. UN Women. Facts and figures: HIV and AIDS. 2018. http://www.unwomen.org/en/what-we-do/hiv-and-aids/fact-and-figures. Accessed 03 Jan 2020.

  3. Sutton MY, Zhou W, Frazier EL. Unplanned pregnancies and contraceptive use among HIV- positive women in care. PLoS One. 2018;13(5):e0197216.

    Article  Google Scholar 

  4. Shah PS, Balkhair T, Ohlsson A, Beyene J, Scott F, Frick C. Intention to become pregnant and low birth weight and preterm birth: a systematic review. Matern Child Health J. 2011 Feb;15(2):205–16.

    Article  Google Scholar 

  5. Brittain K, Phillips TK, Zerbe A, Abrams EJ, Myer L. Long-term effects of unintended pregnancy on antiretroviral therapy outcomes among south African women living with HIV. AIDS. 2019 Apr 1;33(5):885–93.

    Article  CAS  Google Scholar 

  6. Reynolds HW, Janowitz B, Wilcher R, et al. Contraception to prevent HIV-positive births: current contribution and potential cost-savings in PEPFAR countries. Sex Transm Infect. 2008;84(Suppl 2):ii49–53.

    Article  Google Scholar 

  7. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in adults and adolescents with HIV. Department of Health and Human Services. Available at http://www.aidsinfo.nih.gov/ContentFiles/ AdultandAdolescentGL.pdf. Accessed 03 Jan 2020.

  8. Scarsi KK, Darin KM, Chappell CA, Nitz SM, Lamorde M. Drug-drug interactions, effectiveness, and safety of hormonal contraceptives in women living with HIV. Drug Saf. 2016;39(11):1053–72.

    Article  CAS  Google Scholar 

  9. •• Nanda K, et al. Drug interactions between hormonal contraceptives and antiretrovirals. AIDS. 2017;31(7):917–52 This study is the most recent systematic literature review investigating data around pharmacologic and clinical implications of drug-drug interactions between hormonal contraception and anti-retrovirals.

    Article  Google Scholar 

  10. Scarsi KK, Cramer YS, Rosenkranz SL, Aweeka F, Berzins B, Coombs RW, et al. Antiretroviral therapy and vaginally administered contraceptive hormones: a three-arm, pharmacokinetic study. Lancet HIV. 2019;6(9):e601–12.

    Article  Google Scholar 

  11. Scarsi KK, Darin KM, Nakalema S, Back DJ, Byakika-Kibwika P, Else LJ, et al. Unintended pregnancies observed with combined use of the levonorgestrel contraceptive implant and efavirenz-based antiretroviral therapy: a three-arm pharmacokinetic evaluation over 48 weeks. Clin Infect Dis. 2016 Mar 15;62(6):675–82.

    Article  CAS  Google Scholar 

  12. Patel RC, Stalter RM, Thomas KK, Tamraz B, Blue SW, Erikson DW, et al. A pharmacokinetic and pharmacogenetic evaluation of contraceptive implants and antiretroviral therapy among women in Kenya and Uganda. AIDS. 2019;33(13):1995–2004.

    Article  CAS  Google Scholar 

  13. Chappell CA, Lamorde M, Nakalema S, Chen BA, Mackline H, Riddler SA, et al. Efavirenz decreases etonogestrel exposure: a pharmacokinetic evaluation of implantable contraception with antiretroviral therapy. AIDS. 2017 Sep 10;31(14):1965–72.

    Article  CAS  Google Scholar 

  14. Neary M, Lamorde M, Olagunju A, Darin K, Merry C, Byakika-Kibwika P, et al. The effect of gene variants on levonorgestrel pharmacokinetics when combined with antiretroviral therapy containing efavirenz or nevirapine. Clin Pharmacol Ther. 2017;102:529–36.

    Article  CAS  Google Scholar 

  15. •• Patel RC, Onono M, Gandhi M, et al. Pregnancy rates in HIV-positive women using contraceptives and efavirenz-based or nevirapine-based antiretroviral therapy in Kenya: a retrospective cohort study. Lancet HIV. 2015;2(11):e474–82 This retrospective cohort study followed nearly 25,000 patients and is among the largest studies investigating clinical outcomes in HIV-positive women taking hormonal contraceptives. It also provides evidence of possible clinical implications in the interactions between efavirenz and progestin-based implants.

    Article  Google Scholar 

  16. Okoboi S, Eunice A, Oceng R, Etukoit B. Correlation between co-therapy of efavirenz-based ART and pregnancy among HIV-positive women on hormonal contraceptive implants at TASO Tororo-Uganda: A Retrospective Review. J AIDS Clin. 2018;Res 9:759.

    Google Scholar 

  17. Zia, Y., Tang J.H., Chinula L., Tegha G., Stanczyk F.Z., Kourtis A.P. Medroxyprogesterone acetate concentrations among HIV-infected depot-medroxyprogesterone acetate users receiving antiretroviral therapy in Lilongwe, Malawi. Contraception 2019;100(5): 402–405.

  18. Carten ML, Kiser JJ, Kwara A, Mawhinney S, Cu-Uvin S. Pharmacokinetic interactions between the hormonal emergency contraception, levonorgestrel (Plan B), and Efavirenz. Infect Dis Obstet Gynecol. 2012;2012:137192.

    Article  Google Scholar 

  19. Barcellos T, Natavio M, Stanczyk FZ, Luo D, Jusko WJ, Bender NM. Effects of ritonavir-boosted protease inhibitors on combined oral contraceptive pharmacokinetics and pharmacodynamics in HIV-positive women. Contraception. 2019;100(4):283–7.

    Article  CAS  Google Scholar 

  20. Vogler MA, Patterson K, Kamemoto L, Park JG, Watts H, Aweeka F, et al. Contraceptive efficacy of oral and transdermal hormones when co-administered with protease inhibitors in HIV-1-infected women: pharmacokinetic results of ACTG trial A5188. J Acquir Immune Defic Syndr. 2010;55(4):473–82.

    Article  CAS  Google Scholar 

  21. DuBois BN, Atrio J, Stanczyk FZ, Cherala G. Increased exposure of norethindrone in HIV+ women treated with ritonavir-boosted atazanavir therapy. Contraception. 2015;91(1):71–5.

    Article  CAS  Google Scholar 

  22. Robinson JA, et al. Contraception for the HIV-positive woman: a review of interactions between hormonal contraception and antiretroviral therapy. Infect Dis Obstet Gynecol. 2012;890160.

  23. Curtis KM, Tepper NK, Jatlaoui TC, et al. U.S. medical eligibility criteria for contraceptive use, 2016. MMWR Recomm Rep. 2016;65(RR-3):1–104.

    PubMed  Google Scholar 

  24. El-Ibiary SY, Cocohoba JM. Effects of HIV antiretrovirals on the pharmacokinetics of hormonal contraceptives. The European Journal of Contraception & Reproductive Health Care. 2008;13(2):123–32.

    Article  CAS  Google Scholar 

  25. Stuart GS, Moses A, Corbett A, Phiri G, Kumwenda W, Mkandawire N, et al. Pharmacokinetics and pharmacodynamics of a combined oral contraceptive and a generic combined formulation antiretroviral in Malawi. J Acquir Immune Defic Syndr. 2011;58:e40–3.

    Article  Google Scholar 

  26. Patel RC, Baeten JM, Heffron R, Hong T, Davis NL, Nanda K, et al. Brief report: hormonal contraception is not associated with reduced ART effectiveness among women initiating ART: evidence from longitudinal data. J Acquir Immune Defic Syndr. 2017;75(1):91–6.

    Article  Google Scholar 

  27. Chinula L, Nelson JAE, Wiener J, Tang JH, Hurst S, Tegha G, et al. Effect of the depot medroxyprogesterone acetate injectable and levonorgestrel implant on HIV genital shedding: a randomized trial. Contraception. 2018;98(3):193–8.

    Article  CAS  Google Scholar 

  28. Atrio J, Stek A, Vora H, Sanchez-Keeland L, Zannat F, Natavio M. The effect of protease inhibitors on the cervical mucus of HIV-positive women taking norethindrone contraception. Eur J Contracept Reprod Health Care. 2015;20(2):149–53.

    Article  CAS  Google Scholar 

  29. Low AJ, Konate I, Nagot N, Weiss HA, Kania D, Vickerman P, et al. Cervicovaginal HIV-1 shedding in women taking antiretroviral therapy in Burkina Faso: a longitudinal study. J Acquir Immune Defic Syndr. 2014;65(2):237–45.

    Article  CAS  Google Scholar 

  30. Day S, Graham SM, Masese LN, Richardson BA, Kiarie JN, Jaoko W. A prospective cohort study of the effect of depot medroxyprogesterone acetate on detection of plasma and cervical HIV-1 in women initiating and continuing antiretroviral therapy. J Acquir Immune Defic Syndr. 2014;66:452–6.

    Article  CAS  Google Scholar 

  31. •• Roberts O, Rajoli R, et al. Physiologically based pharmacokinetic modelling prediction of the effects of dose adjustment in drug–drug interactions between levonorgestrel contraceptive implants and efavirenz-based ART. Journal of Antimicrobial Chemotherapy. 2018;73(4):1004–12 This study provides a model for drug dose adjustment for patients taking both hormonal contraception and anti-retrovirals with potential interactions.

    Article  CAS  Google Scholar 

  32. Tweya H, Feldacker C, Gugsa S, Phiri S. Contraceptive use and pregnancy rates among women receiving antiretroviral therapy in Malawi: a retrospective cohort study. Reprod Health. 2018;15(1):25.

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Gynecology and Obstetrics, Emory University School of Medicine, 49 Jesse Hill Jr. Drive SE, Faculty Office Building, Atlanta, GA, 30303, USA

    Gopika R. Krishna & Lisa B. Haddad

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  1. Gopika R. Krishna
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Correspondence to Lisa B. Haddad.

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This article is part of the Topical Collection on Family Planning

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Krishna, G.R., Haddad, L.B. Interactions Between Hormonal Contraception and Anti-Retroviral Therapy: an Updated Review. Curr Obstet Gynecol Rep 9, 98–104 (2020). https://doi.org/10.1007/s13669-020-00289-7

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