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Open Access 21-06-2023 | Human Immunodeficiency Virus

Update on the Impact of Depot Medroxyprogesterone Acetate on Vaginal Mucosal Endpoints and Relevance to Sexually Transmitted Infections

Authors: Smritee Dabee, Christina Balle, Maricianah Onono, Steve Innes, Gonasagrie Nair, Thesla Palanee-Phillips, Adam D. Burgener, Steven E. Bosinger, Jo-Ann S. Passmore, Renee Heffron, Heather Jaspan, Anna-Ursula Happel

Published in: Current HIV/AIDS Reports | Issue 4/2023

Abstract

Purpose of Review

The long-acting reversible intramuscularly-injected contraceptive depot medroxyprogesterone acetate (DMPA-IM) is widely used by cisgender women in Africa. Although DMPA-IM provides reliable contraception, potential effects on the female genital tract (FGT) mucosa have raised concern, including risk of HIV infection. This review summarises and compares evidence from observational cohort studies and the randomised Evidence for Contraceptive Options in HIV Outcomes (ECHO) Trial.

Recent Findings

Although previous observational studies found women using DMPA-IM had higher abundance of bacterial vaginosis (BV)-associated bacteria, increased inflammation, increased cervicovaginal HIV target cell density, and epithelial barrier damage, sub-studies of the ECHO Trial found no adverse changes in vaginal microbiome, inflammation, proteome, transcriptome, and risk of viral and bacterial STIs, other than an increase in Th17-like cells.

Summary

Randomised data suggest that DMPA-IM use does not adversely change mucosal endpoints associated with acquisition of infections. These findings support the safe use of DMPA-IM in women at high risk of acquiring STIs, including HIV.

Graphical Abstract

Alkema L, Kantorova V, Menozzi C, Biddlecom A. National, regional, and global rates and trends in contraceptive prevalence and unmet need for family planning between 1990 and 2015: a systematic and comprehensive analysis. Lancet [Internet]. 2013;381:1642–52. Available from: https://www.sciencedirect.com/science/article/pii/S0140673612622041. Accessed 28 Nov 2022

Tsui AO, Brown W, Li Q. Contraceptive practice in sub-Saharan Africa. Popul Dev Rev [Internet]. 2017;43:166–91. Available from: https://doi.org/10.1111/padr.12051.

Smith JA, Heffron R, Butler AR, Celum C, Baeten JM, Hallett TB. Could misreporting of condom use explain the observed association between injectable hormonal contraceptives and HIV acquisition risk? Contraception. 2017;95:424–30.CrossRefPubMedPubMedCentral

Baeten JM, Heffron R. Contraception and sexually transmitted infections: risks and benefits, hypotheses and evidence. Lancet Glob Health. 2015;3:e430–1.CrossRefPubMed

Polis CB, Curtis KM, Hannaford PC, Phillips SJ, Chipato T, Kiarie JN, Westreich DJ, Steyn PS. An updated systematic review of epidemiological evidence on hormonal contraceptive methods and HIV acquisition in women. AIDS. 2016;30(17):2665–83. https://doi.org/10.1097/QAD.0000000000001228.

Morrison CS, Chen P-L, Kwok C, Baeten JM, Brown J, Crook AM, et al. Hormonal contraception and the risk of HIV acquisition: an individual participant data meta-analysis. PLoS Med [Internet].; 2015;12:e1001778-. Available from: https://doi.org/10.1371/journal.pmed.1001778.

Ahmed K, Baeten JM, Beksinska M, Bekker L-G, Bukusi EA, Donnell D, et al. HIV incidence among women using intramuscular depot medroxyprogesterone acetate, a copper intrauterine device, or a levonorgestrel implant for contraception: a randomised, multicentre, open-label trial. The Lancet [Internet]. 2019;394:303–13. Available from: https://doi.org/10.1016/S0140-6736(19)31288-7.

•• Curtis KM, Hannaford PC, Rodriguez MI, Chipato T, Steyn PS, Kiarie JN. Hormonal contraception and HIV acquisition among women: an updated systematic review. BMJ Sex Reprod Health [Internet]. 2020;46:8. Available from: http://jfprhc.bmj.com/content/46/1/8.abstract. This is an updated systematic review on hormonal contraception and HIV acquisition. Accessed 15 Nov 2022

•• Tanko RF, Bunjun R, Dabee S, Jaumdally SZ, Onono M, Nair G, et al. The effect of contraception on genital cytokines in women randomized to copper intrauterine device, depot medroxyprogesterone acetate, or levonorgestrel implant . J Infect Dis [Internet]. 2022;226:907–19. Available from: https://doi.org/10.1093/infdis/jiac084. This biomedical ECHO sub-study showed that DMPA-IM use does not increase cervico-vaginal cytokines levels at 1- and 6-month post-contraceptive initiation compared to pre-initiation.

10.

•• Bunjun R, Ramla TF, Jaumdally SZ, Noël-Romas L, Ayele H, Brown BP, et al. Initiating Intramuscular Depot Medroxyprogesterone Acetate (DMPA-IM) Increases frequencies of Th17-like human immunodeficiency virus (HIV) target cells in the genital tract of women in South Africa: a randomized trial. Clin Infect Dis [Internet]. 2022;ciac284. Available from: https://doi.org/10.1093/cid/ciac284. This biomedical ECHO sub-study showed that DMPA-IM use was associated with higher frequencies of cervical Th17-like cells at 1-month post-initiation, which as accompanied by enhanced mucosal barrier function as measured by proteomics.

11.

•• Mugo NR, Stalter RM, Heffron R, Rees H, Scoville CW, Morrison C, et al. Incidence of herpes simplex virus type 2 infection among African women using depot medroxyprogesterone acetate, a copper intrauterine device, or a levonorgestrel implant for contraception: a nested randomized trial . Clin Infect Dis [Internet]. 2022;75:586–95. Available from: https://doi.org/10.1093/cid/ciab1027. This ECHO sub-study showed that DMPA-IM use was not associated with increased risk of HSV-2 acquisition.

12.

•• Deese J, Philip N, Lind M, Ahmed K, Batting J, Beksinska M, et al. Sexually transmitted infections among women randomised to depot medroxyprogesterone acetate, a copper intrauterine device or a levonorgestrel implant. Sex Transm Infect [Internet]. 2021;97:249–55. Available from: https://sti.bmj.com/content/97/4/249. This ECHO sub-study showed that DMPA-IM use was associated with lower chlamydia and gonorrhoea risk compared to implant and copper-IUD use, respectively.

13.

•• Brown BP, Feng C, Tanko RF, Jaumdally SZ, Bunjun R, Dabee S, et al. Copper intrauterine device increases vaginal concentrations of inflammatory anaerobes and depletes lactobacilli compared to hormonal options in a randomized trial. Nat Commun [Internet]. 2023;14:499. Available from: https://doi.org/10.1038/s41467-023-36002-4. This biomedical ECHO sub-study showed that DMPA-IM use was not associated with shifts in bacterial diversity at 1- and 6-months post-contraceptive initiation, and that a shift from L. iners to L. crispatus dominated microbiotas at 6-months post-contraceptive initiation was common amongst DMPA-IM users.

14.

Ayele H, Romas LN, Birse K, Horne S, Onono M, Nair G, Palanee-Phillips T, Tanko R, Bunjun R, Arnold KB, McCorrister S. The impact of progestin-based contraceptive initiation on the cervicovaginal proteome in participants from the ECHO trial. In: Journal of the international aids society. The atrium, southern gate, chichester. England: John Wiley & Sons Ltd; 2021. p. 54.

15.

McKinnon LR, Achilles SL, Bradshaw CS, Burgener A, Crucitti T, Fredricks DN, et al. The evolving facets of bacterial vaginosis: implications for HIV transmission. AIDS Res Hum Retroviruses [Internet]. 2019;35:219–28. Available from: https://www.ncbi.nlm.nih.gov/pubmed/30638028. Accessed 06 Dec 2019

16.

Atashili J, Poole C, Ndumbe PM, Adimora A, a, Jennifer S. Bacterial vaginosis and HIV acquisition: a meta-analysis of published studies. AIDS. 2008;22:1493–501.CrossRefPubMed

17.

Cohen CR, Lingappa JR, Baeten JM, Ngayo MO, Spiegel CA, Hong T, et al. Bacterial vaginosis associated with increased risk of female-to-male HIV-1 transmission: a prospective cohort analysis among African couples. PLoS Med [Internet]. 2012;9:e1001251. Available from: https://doi.org/10.1371/journal.pmed.1001251.

18.

Gosmann C, Anahtar MN, Handley SA, Farcasanu M, Abu-Ali G, Bowman BA, et al. Lactobacillus-deficient cervicovaginal bacterial communities are associated with increased HIV acquisition in young South African women. Immunity [Internet]. 2017;46:29–37. Available from: https://www.ncbi.nlm.nih.gov/pubmed/28087240. Accessed 06 Dec 2019

19.

McClelland RS, Lingappa JR, Srinivasan S, Kinuthia J, John-Stewart GC, Jaoko W, et al. Evaluation of the association between the concentrations of key vaginal bacteria and the increased risk of HIV acquisition in African women from five cohorts: a nested case-control study. Lancet Infect Dis [Internet]. 2018;18:554–64. Available from: https://doi.org/10.1016/S1473-3099(18)30058-6.

20.

Thurman A, Chandra N, Schwartz JL, Brache V, Chen BA, Asin S, et al. The effect of hormonal contraception on cervicovaginal mucosal end points associated with HIV acquisition. AIDS Res Hum Retroviruses [Internet]. 2019;35:853–64. Available from: https://doi.org/10.1089/aid.2018.0298.

21.

Jespers V, Crucitti T, Menten J, Verhelst R, Mwaura M, Mandaliya K, et al. Prevalence and correlates of bacterial vaginosis in different sub-populations of women in Sub-Saharan Africa: a cross-sectional study. PLoS One [Internet]. 2014;9:e109670-. Available from: https://doi.org/10.1371/journal.pone.0109670.

22.

Haddad LB, Wall KM, Tote K, Kilembe W, Vwailika B, Sharkey T, et al. Hormonal contraception and vaginal infections among couples who are human immunodeficiency virus serodiscordant in Lusaka, Zambia. Obstet Gynecol [Internet]. 2019;134. Available from: https://journals.lww.com/greenjournal/Fulltext/2019/09000/Hormonal_Contraception_and_Vaginal_Infections.20.aspx. Accessed 18 Nov 2022

23.

Bradshaw CS, Vodstrcil LA, Hocking JS, Law M, Pirotta M, Garland SM, et al. Recurrence of bacterial vaginosis is significantly associated with posttreatment sexual activities and hormonal contraceptive use. Clin Infect Dis [Internet]. 2013;56:777–86. Available from: https://doi.org/10.1093/cid/cis1030.

24.

van de Wijgert JHHM, Verwijs MC, Turner AN, Morrison CS. Hormonal contraception decreases bacterial vaginosis but oral contraception may increase candidiasis: implications for HIV transmission. AIDS [Internet]. 2013;27. Available from: https://journals.lww.com/aidsonline/Fulltext/2013/08240/Hormonal_contraception_decreases_bacterial.14.aspx. Accessed 18 Nov 2022

25.

Vodstrcil LA, Hocking JS, Law M, Walker S, Tabrizi SN, Fairley CK, et al. Hormonal contraception is associated with a reduced risk of bacterial vaginosis: a systematic review and meta-analysis. PLoS One [Internet]. 2013;8:e73055-. Available from: https://doi.org/10.1371/journal.pone.0073055.

26.

Roxby AC, Fredricks DN, Odem-Davis K, Ásbjörnsdóttir K, Masese L, Fiedler TL, et al. Changes in vaginal microbiota and immune mediators in HIV-1-seronegative Kenyan women initiating depot medroxyprogesterone acetate. J Acquir Immune Defic Syndr. 2016;71:359–66.CrossRefPubMedPubMedCentral

27.

Whitney BM, Guthrie BL, Srinivasan S, Tapia K, Muriuki EM, Chohan BH, et al. Changes in key vaginal bacteria among postpartum African women initiating intramuscular depot-medroxyprogesterone acetate. PLoS One [Internet]. 2020;15:e0229586-. Available from: https://doi.org/10.1371/journal.pone.0229586.

28.

Borgdorff H, Verwijs MC, Wit FWNM, Tsivtsivadze E, Ndayisaba GF, Verhelst R, et al. The impact of hormonal contraception and pregnancy on sexually transmitted infections and on cervicovaginal microbiota in African sex workers. Sex Transm Dis [Internet]. 2015;42:143–52. Available from: https://www.jstor.org/stable/48511882. Accessed 18 Nov 2022

29.

Kazi YF, Saleem S, Kazi N. Investigation of vaginal microbiota in sexually active women using hormonal contraceptives in Pakistan. BMC Urol [Internet]. 2012;12:22. Available from: https://doi.org/10.1186/1471-2490-12-22.

30.

Achilles SL, Austin MN, Meyn LA, Mhlanga F, Chirenje ZM, Hillier SL. Impact of contraceptive initiation on vaginal microbiota. Am J Obstet Gynecol. 2018;218:622.e1–622.e10.CrossRefPubMed

31.

Brooks JP, Edwards DJ, Blithe DL, Fettweis JM, Serrano MG, Sheth NU, et al. Effects of combined oral contraceptives, depot medroxyprogesterone acetate and the levonorgestrel-releasing intrauterine system on the vaginal microbiome. Contraception. 2017;95:405–13.CrossRefPubMed

32.

Jespers V, Kyongo J, Joseph S, Hardy L, Cools P, Crucitti T, et al. A longitudinal analysis of the vaginal microbiota and vaginal immune mediators in women from sub-Saharan Africa. Sci Rep. 2017;7:11974.CrossRefPubMedPubMedCentral

33.

Song S, Acharya K, Zhu J, Deveney C, Walther-Antonio MR, Tetel M, et al. Daily vaginal microbiota fluctuations associated with natural hormonal cycle, contraceptives, diet, and exercise. mSphere [Internet]. 2020;5:e00593-20. Available from: https://doi.org/10.1128/mSphere.00593-20.

34.

Mitchell CM, McLemore L, Westerberg K, Astronomo R, Smythe K, Gardella C, et al. Long-term effect of depot medroxyprogesterone acetate on vaginal microbiota, epithelial thickness and HIV target cells. J Infect Dis [Internet]. 2014;210:651–5. Available from: https://doi.org/10.1093/infdis/jiu176.

35.

Wessels JM, Lajoie J, Cooper MIJH, Omollo K, Felker AM, Vitali D, et al. Medroxyprogesterone acetate alters the vaginal microbiota and microenvironment in women and increases susceptibility to HIV-1 in humanized mice. Dis Model Mech [Internet]. 2019;12:dmm039669. Available from: https://doi.org/10.1242/dmm.039669.

36.

Lisa B Haddad, Jennifer H Tang, Nicole L Davis, Athena P Kourtis, Lameck Chinula, Albans Msika, et al. Influence of hormonal contraceptive use and HIV on cervicovaginal cytokines and microbiota in Malawi. mSphere [Internet]. 2023;0:e00585-22. Available from: https://doi.org/10.1128/msphere.00585-22.

37.

Passmore J-AS, Jaspan HB, Masson L. Genital inflammation, immune activation and risk of sexual HIV acquisition. Curr Opin HIV AIDS [Internet]. 2016;11:156–62. Available from: https://pubmed.ncbi.nlm.nih.gov/26628324. Accessed 18 Dec 2020

38.

Liebenberg LJP, Masson L, Arnold KB, Mckinnon LR, Werner L, Proctor E, et al. Genital — systemic chemokine gradients and the risk of HIV acquisition in women. J Acquir Immune Defic Syndr. 2017;74:318–25.CrossRefPubMedPubMedCentral

39.

Masson L, Passmore J-AS, Liebenberg LJ, Werner L, Baxter C, Arnold KB, Williamson C, Little F, Mansoor LE, Naranbhai V, Lauffenburger DA, Ronacher K, Walzl G, Garrett NJ, Williams BL, Couto-Rodriguez M, Hornig M, Lipkin WI, Grobler A, Abdool Karim SS. Genital inflammation and the risk of HIV acquisition in women. Clinical Infectious Diseases. 2015;61(2):260–9. https://doi.org/10.1093/cid/civ298.

40.

McKinnon LR, Liebenberg LJ, Yende-Zuma N, Archary D, Ngcapu S, Sivro A, et al. Genital inflammation undermines the effectiveness of tenofovir gel in preventing HIV acquisition in women. Nat Med. 2018;24:491–6.CrossRefPubMedPubMedCentral

41.

Mlisana K, Naicker N, Werner L, Roberts L, van Loggerenberg F, Baxter C, et al. Symptomatic vaginal discharge is a poor predictor of sexually transmitted infections and genital tract inflammation in high-risk women in South Africa. J Infect Dis. 2012;206:6–14.CrossRefPubMedPubMedCentral

42.

Happel A-U, Sivro A, Liebenberg L, Passmore JA, Mitchell CM. Considerations for choosing soluble immune markers to determine safety of novel vaginal products. Front Reprod Health [Internet]. 2022;4. Available from: https://www.frontiersin.org/articles/10.3389/frph.2022.899277. Accessed 18 Nov 2022

43.

Dabee S, Barnabas SL, Lennard KS, Jaumdally SZ, Gamieldien H, Balle C, et al. Defining characteristics of genital health in South African adolescent girls and young women at high risk for HIV infection. PLoS One [Internet]. 2019;14:e0213975–e0213975. Available from: https://www.ncbi.nlm.nih.gov/pubmed/30947260. Accessed 06 Dec 2019

44.

Deese J, Masson L, Miller W, Cohen M, Morrison C, Wang M, et al. Injectable progestin-only contraception is associated with increased levels of pro-inflammatory cytokines in the female genital tract. Am J Reprod Immunol. 2015;2015(74):357–67.CrossRef

45.

Francis SC, Hou Y, Baisley K, van de Wijgert J, Watson-Jones D, Ao TT, Herrera C, Maganja K, Andreasen A, Kapiga S, Coulton GR. Immune activation in the female genital tract: expression profiles of soluble proteins in women at high risk for HIV infection. PloS one. 2016;11(1):e0143109.

46.

Morrison CS, Fichorova R, Chen P-L, Kwok C, Deese J, Yamamoto H, et al. A longitudinal assessment of cervical inflammation and immunity associated with HIV-1 infection, hormonal contraception, and pregnancy. AIDS Res Hum Retroviruses. 2018;34:889–99.CrossRefPubMedPubMedCentral

47.

Huijbregts RPH, Helton ES, Michel KG, Sabbaj S, Richter HE, Goepfert PA, et al. Hormonal contraception and HIV-1 infection: medroxyprogesterone acetate suppresses innate and adaptive immune mechanisms. Endocrinology. 2013;154:1282–95.CrossRefPubMedPubMedCentral

48.

Ngcapu S, Masson L, Sibeko S, Werner L, McKinnon LR, Mlisana K, et al. Lower concentrations of chemotactic cytokines and soluble innate factors in the lower female genital tract associated with the use of injectable hormonal contraceptive. J Reprod Immunol. 2015;110:14–21.CrossRefPubMedPubMedCentral

49.

Michel KG, Huijbregts RPH, Gleason JL, Richter HE, Hel Z. Effect of hormonal contraception on the function of plasmacytoid dendritic cells and distribution of immune cell populations in the female reproductive tract. J Acquir Immune Defic Syndr. 2015;68:511–8.CrossRefPubMedPubMedCentral

50.

Tasker C, Pizutelli V, Lo Y, Ramratnam B, Roche NE, Chang TL. Depot medroxyprogesterone acetate administration increases cervical CCR5+CD4+ T cells and induces immunosuppressive milieu at the cervicovaginal mucosa. AIDS [Internet]. 2020;34. Available from: https://journals.lww.com/aidsonline/Fulltext/2020/04010/Depot_medroxyprogesterone_acetate_administration.9.aspx. Accessed 18 Nov 2022

51.

Smith-McCune KK, Hilton JF, Shanmugasundaram U, Critchfield JW, Greenblatt RM, Seidman D, et al. Effects of depot-medroxyprogesterone acetate on the immune microenvironment of the human cervix and endometrium: implications for HIV susceptibility. Mucosal Immunol [Internet]. 2017;10:1270–8. Available from: https://doi.org/10.1038/mi.2016.121.

52.

Achilles SL, Meyn LA, Mhlanga FG, Matubu AT, Stoner KA, Beamer MA, et al. Zim CHIC: a cohort study of immune changes in the female genital tract associated with initiation and use of contraceptives. Am J Reprod Immunol [Internet]. 2020;84:e13287. Available from: https://doi.org/10.1111/aji.13287.

53.

Omollo K, Lajoie J, Oyugi J, Wessels JM, Mwaengo D, Kimani J, et al. Differential elevation of inflammation and CD4+ T cell activation in Kenyan female sex workers and non-sex workers using depot-medroxyprogesterone acetate. Front Immunol [Internet]. 2021;11. Available from: https://www.frontiersin.org/articles/10.3389/fimmu.2020.598307. Accessed 15 Nov 2022

54.

Molatlhegi RP, Liebenberg LJ, Leslie A, Noel-Romas L, Mabhula A, Mchunu N, et al. Plasma concentration of injectable contraceptive correlates with reduced cervicovaginal growth factor expression in South African women. Mucosal Immunol [Internet]. 2020;13:449–59. Available from: https://doi.org/10.1038/s41385-019-0249-y.

55.

Byrne EH, Anahtar MN, Cohen KE, Moodley A, Padavattan N, Ismail N, et al. Association between injectable progestin-only contraceptives and HIV acquisition and HIV target cell frequency in the female genital tract in South African women: a prospective cohort study. Lancet Infect Dis [Internet]. 2016;16:441–8. Available from: https://doi.org/10.1016/S1473-3099(15)00429-6.

56.

•• Radzey N, Harryparsad R, Meyer B, Chen PL, Gao X, Morrison C, et al. Genital inflammatory status and the innate immune response to contraceptive initiation. Am J Reprod Immunol [Internet]. 2022;88:e13542. Available from: https://doi.org/10.1111/aji.13542. This biomedical ECHO sub-study showed that DMPA-IM use does not increase cervico-vaginal cytokines levels at 1- and 3-month post-contraceptive initiation compared to pre-initiation.

57.

Monin L, Whettlock EM, Male V. Immune responses in the human female reproductive tract. Immunology [Internet]. 2020;160:106–15. Available from: https://doi.org/10.1111/imm.13136.

58.

Alvarez Y, Tuen M, Shen G, Nawaz F, Arthos J, Wolff MJ, et al. Preferential HIV infection of CCR6+ Th17 cells is associated with higher levels of virus receptor expression and lack of CCR5 ligands. J Virol. 2013;87:10843–54.CrossRefPubMedPubMedCentral

59.

Sun H, Kim D, Li X, Kiselinova M, Ouyang Z, Vandekerckhove L, et al. Th1/17 polarization of CD4 T cells supports HIV-1 persistence during antiretroviral therapy. J Virol. 2015;89:11284–93.CrossRefPubMedPubMedCentral

60.

Lajoie J, Tjernlund A, Omollo K, Edfeldt G, Röhl M, Boily-Larouche G, et al. Increased cervical CD4+CCR5+ T cells among Kenyan sex working women using depot medroxyprogesterone acetate. AIDS Res Hum Retroviruses [Internet]. 2018;35:236–46. Available from: https://doi.org/10.1089/aid.2018.0188. Accessed 18 Nov 2022

61.

Ildgruben AK, Sjöberg IM, Hammarström M-LKC. Influence of hormonal contraceptives on the immune cells and thickness of human vaginal epithelium. Obstet Gynecol [Internet]. 2003;102:571–82. Available from: https://www.sciencedirect.com/science/article/pii/S0029784403006185. Accessed 18 Nov 2022.

62.

Edfeldt G, Lajoie J, Röhl M, Oyugi J, Åhlberg A, Khalilzadeh-Binicy B, et al. Regular use of depot medroxyprogesterone acetate causes thinning of the superficial lining and apical distribution of human immunodeficiency virus target cells in the human ectocervix. J Infect Dis [Internet]. 2022;225:1151–61. Available from: https://doi.org/10.1093/infdis/jiaa514.

63.

Chandra N, Thurman AR, Anderson S, Cunningham TD, Yousefieh N, Mauck C, et al. Depot medroxyprogesterone acetate increases immune cell numbers and activation markers in human vaginal mucosal tissues. AIDS Res Hum Retroviruses [Internet]. 2012;29:592–601. Available from: https://doi.org/10.1089/aid.2012.0271.

64.

Li L, Zhou J, Wang W, Huang L, Tu J, Baiamonte L, et al. Effects of three long-acting reversible contraceptive methods on HIV target cells in the human uterine cervix and peripheral blood. Reprod Biol Endocrinol [Internet]. 2019;17:26. Available from: https://doi.org/10.1186/s12958-019-0469-8.

65.

Carias A, Hope T. Barriers of mucosal entry of HIV/SIV. Curr Immunol Rev. 2019;5:4–13.CrossRef

66.

67.

Keller MJ, Guzman E, Hazrati E, Kasowitz A, Cheshenko N, Wallenstein S, et al. PRO 2000 elicits a decline in genital tract immune mediators without compromising intrinsic antimicrobial activity. AIDS. 2007;21:467–76.CrossRefPubMed

68.

Haddad LB, Swaims-Kohlmeier A, Mehta CC, Haaland RE, Brown NL, Sheth AN, et al. Impact of etonogestrel implant use on T-cell and cytokine profiles in the female genital tract and blood. PLoS One. 2020;15:e0230473.CrossRefPubMedPubMedCentral

69.

Birse KD, Romas LM, Guthrie BL, Nilsson P, Bosire R, Kiarie J, et al. Genital injury signatures and microbiome alterations associated with depot medroxyprogesterone acetate usage and intravaginal drying practices. J Infect Dis. 2017;215:590–8.PubMed

70.

Vincent AJ, Zhang J, Ostör A, Rogers PAW, Affandi B, Kovacs G, et al. Decreased tissue inhibitor of metalloproteinase in the endometrium of women using depot medroxyprogesterone acetate: a role for altered endometrial matrix metalloproteinase/tissue inhibitor of metalloproteinase balance in the pathogenesis of abnormal ute. Hum Reprod. 2002;17:1189–98.CrossRefPubMed

71.

Zalenskaya IA, Chandra N, Yousefieh N, Fang X, Adedipe OE, Jackson SS, et al. Use of contraceptive depot medroxyprogesterone acetate is associated with impaired cervicovaginal mucosal integrity. J Clin Invest. 2018;128:4622–38.CrossRefPubMedPubMedCentral

72.

Calla NEQ, Miguel RDV, Boyaka PN, Hall-stoodley L, Kaur B, Trout W, et al. Medroxyprogesterone acetate and levonorgestrel increase genital mucosal permeability and enhance susceptibility to genital herpes simplex virus type 2 infection. Mucosal Immunol. 2016;9:1571–83.CrossRefPubMedCentral

73.

Goldfien GA, Barragan F, Chen J, Takeda M, Irwin JC, Perry J, et al. Progestin-containing contraceptives alter expression of host defense-related genes of the endometrium and cervix. Reprod Sci [Internet]. 2015;22:814–28. Available from: https://doi.org/10.1177/1933719114565035.

74.

Edfeldt G, Lajoie J, Röhl M, Oyugi J, Åhlberg A, Khalilzadeh-Binicy B, Bradley F, Mack M, Kimani J, Omollo K, Wählby C. Regular use of depot medroxyprogesterone acetate causes thinning of the superficial lining and apical distribution of human immunodeficiency virus target cells in the human ectocervix. The Journal of Infectious Diseases. 2022;225(7):1151–61.

75.

Bahamondes L, Trevisan M, Andrade L, Marchi NM, Castro S, Dı́az J, et al. The effect upon the human vaginal histology of the long-term use of the injectable contraceptive Depo-Provera. Contraception [Internet]. 2000;62:23–7. Available from: https://doi.org/10.1016/S0010-7824(00)00132-3.

76.

Slifer ZM, Blikslager AT. The integral role of tight junction proteins in the repair of injured intestinal epithelium. Int J Mol Sci [Internet]. 2020;21. Available from: https://www.mdpi.com/1422-0067/21/3/972. Accessed 16 Feb 2023

77.

Wu G, Grassi P, MacIntyre DA, Molina BG, Sykes L, Kundu S, et al. N-glycosylation of cervicovaginal fluid reflects microbial community, immune activity, and pregnancy status. Sci Rep [Internet]. 2022;12:16948. Available from: https://doi.org/10.1038/s41598-022-20608-7.

78.

Agarwal K, Choudhury B, Robinson LS, Allsworth JE, Lewis AL, Lewis WG. Resident microbes shape the vaginal epithelial glycan landscape. medRxiv [Internet]. 2022;2022.02.23.22271417. Available from: http://medrxiv.org/content/early/2022/02/24/2022.02.23.22271417.abstract. Accessed 16 Feb 2023

79.

Barker EK, Malekinejad M, Merai R, Lyles CM, Sipe TA, DeLuca JB, et al. Risk of human immunodeficiency virus acquisition among high-risk heterosexuals with nonviral sexually transmitted infections: a systematic review and meta-analysis. Sex Transm Dis [Internet]. 2022;49. Available from: https://journals.lww.com/stdjournal/Fulltext/2022/06000/Risk_of_Human_Immunodeficiency_Virus_Acquisition.1.aspx. Accessed 18 Nov 2022

80.

Looker KJ, Rönn MM, Brock PM, Brisson M, Drolet M, Mayaud P, et al. Evidence of synergistic relationships between HIV and human papillomavirus (HPV): systematic reviews and meta-analyses of longitudinal studies of HPV acquisition and clearance by HIV status, and of HIV acquisition by HPV status. J Int AIDS Soc [Internet]. 2018;21:e25110. Available from: https://doi.org/10.1002/jia2.25110.

81.

Looker KJ, Welton NJ, Sabin KM, Dalal S, Vickerman P, Turner KME, et al. Global and regional estimates of the contribution of herpes simplex virus type 2 infection to HIV incidence: a population attributable fraction analysis using published epidemiological data. Lancet Infect Dis [Internet]. 2020;20:240–9. Available from: https://doi.org/10.1016/S1473-3099(19)30470-0.

82.

McCarthy KJ, Gollub EL, Ralph L, van de Wijgert J, Jones HE. Hormonal contraceptives and the acquisition of sexually transmitted infections: an updated systematic review. Sex Transm Dis [Internet]. 2019;46. Available from: https://journals.lww.com/stdjournal/Fulltext/2019/05000/Hormonal_Contraceptives_and_the_Acquisition_of.3.aspx. Accessed 15 Nov 2022

83.

Deese J, Pradhan S, Goetz H, Morrison CS. Contraceptive use and the risk of sexually transmitted infection: systematic review and current perspectives. Open Access J Contracept. 2018;9:91–112.CrossRefPubMedPubMedCentral

Title: Update on the Impact of Depot Medroxyprogesterone Acetate on Vaginal Mucosal Endpoints and Relevance to Sexually Transmitted Infections
Authors: Smritee Dabee
Christina Balle
Maricianah Onono
Steve Innes
Gonasagrie Nair
Thesla Palanee-Phillips
Adam D. Burgener
Steven E. Bosinger
Jo-Ann S. Passmore
Renee Heffron
Heather Jaspan
Anna-Ursula Happel
Publication date: 21-06-2023
Publisher: Springer US
Keywords: Human Immunodeficiency Virus
Respiratory Microbiota
Medroxyprogesterone Acetate
Published in: Current HIV/AIDS Reports / Issue 4/2023
Print ISSN: 1548-3568
Electronic ISSN: 1548-3576
DOI: https://doi.org/10.1007/s11904-023-00662-0

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