Download PDF
Semin Reprod Med 2016; 34(03): 159-167
DOI: 10.1055/s-0036-1571436
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Emerging Technologies to Prevent Pregnancy and Sexually Transmitted Infections in Women

Dominika Seidman
1   Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San Francisco, San Francisco, California
2   Bixby Center for Global Reproductive Health, University of California San Francisco, San Francisco, California
,
Anke Hemmerling
1   Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San Francisco, San Francisco, California
2   Bixby Center for Global Reproductive Health, University of California San Francisco, San Francisco, California
,
Karen Smith-McCune
1   Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San Francisco, San Francisco, California
› Author Affiliations
Further Information

Publication History

Publication Date:
08 March 2016 (online)

    Permissions and Reprints

Abstract

Worldwide, there continues to be a large unmet need for family planning and sexually transmitted infection (STI) prevention methods. Multipurpose prevention technology (MPT) is a general term encompassing any single prevention methodology targeting more than one STI (including HIV) and/or pregnancy. While innovation has been slow over the past several decades, recent scientific advances have resulted in new products entering clinical trials. This review focuses primarily on multipurpose technologies that are designed to prevent pregnancy and HIV. To examine the current state of MPTs, we outline key discoveries of biologic mechanisms that influence susceptibility of the female genital tract to HIV and STIs, and review the effects of hormonal contraception on HIV susceptibility. We discuss the state of currently available HIV prevention strategies for women, and their interactions with hormonal contraceptive products. Finally, we describe MPTs currently in preclinical and clinical trials and propose ongoing questions requiring research to help advance the field.

Keywords

multipurpose prevention technology - contraception - HIV/AIDS - sexually transmitted infection
 

  • References

  • 1 Boonstra H. Multipurpose prevention technologies for the developing world: U.S. investment is critical. Guttmacher Policy Rev 2015; 18 (3) xx
    PubMedGoogle Scholar
  • 2 Sedgh G, Singh S, Hussain R. Intended and unintended pregnancies worldwide in 2012 and recent trends. Stud Fam Plann 2014; 45 (3) 301-314
    CrossrefPubMedGoogle Scholar
  • 3 UNAIDS. Core Epidemiology Slides - July 2015. 2015; http://www.unaids.org/en/resources/documents/2015/20150714_coreepidemiologyslides_ppt . Accessed October 13, 2015
    PubMedGoogle Scholar
  • 4 Schelar E, Polis CB, Essam T , et al. Multipurpose prevention technologies for sexual and reproductive health: mapping global needs for introduction of new preventive products. Contraception 2015; 15: 577-677
    PubMedGoogle Scholar
  • 5 Global Incidence and Prevalence of Selected Curable Sexually Transmitted Infections – 2008. Geneva: World Health Organization; 2012
    Google Scholar
  • 6 USAID. Open Forum on Condom Promotion and Dual Protection. Meeting Report, February 21, 2001, Washington, DC. 2001; Available at: http://www.popline.org/node/178134%5D . Accessed October 13, 2015
    PubMedGoogle Scholar
  • 7 Young Holt B, Romano J, Manning J , et al. Ensuring successful development and introduction of multipurpose prevention technologies through an innovative partnership approach. BJOG 2014; 121 (Suppl. 05) 3-8
    PubMedGoogle Scholar
  • 8 Wira CR, Rodriguez-Garcia M, Patel MV. The role of sex hormones in immune protection of the female reproductive tract. Nat Rev Immunol 2015; 15 (4) 217-230
    CrossrefPubMedGoogle Scholar
  • 9 Wira CR, Fahey JV. A new strategy to understand how HIV infects women: identification of a window of vulnerability during the menstrual cycle. AIDS 2008; 22 (15) 1909-1917
    CrossrefPubMedGoogle Scholar
  • 10 Murphy K, Irvin SC, Herold BC. Research gaps in defining the biological link between HIV risk and hormonal contraception. Am J Reprod Immunol 2014; 72 (2) 228-235
    CrossrefPubMedGoogle Scholar
  • 11 Polis CB, Curtis KM. Use of hormonal contraceptives and HIV acquisition in women: a systematic review of the epidemiological evidence. Lancet Infect Dis 2013; 13 (9) 797-808
    CrossrefPubMedGoogle Scholar
  • 12 Polis CB, Westreich D, Balkus JE, Heffron R ; Participants of the 2013 HC-HIV Observational Analysis Meeting. Assessing the effect of hormonal contraception on HIV acquisition in observational data: challenges and recommended analytic approaches. AIDS 2013; 27 (Suppl. 01) S35-S43
    CrossrefPubMedGoogle Scholar
  • 13 Ralph LJ, McCoy SI, Shiu K, Padian NS. Hormonal contraceptive use and women's risk of HIV acquisition: a meta-analysis of observational studies. Lancet Infect Dis 2015; 15 (2) 181-189
    CrossrefPubMedGoogle Scholar
  • 14 Morrison CS, Chen PL, Kwok C , et al. Hormonal contraception and the risk of HIV acquisition: an individual participant data meta-analysis. PLoS Med 2015; 12 (1) e1001778
    CrossrefPubMedGoogle Scholar
  • 15 Polis CB, Phillips SJ, Curtis KM , et al. Hormonal contraceptive methods and risk of HIV acquisition in women: a systematic review of epidemiological evidence. Contraception 2014; 90 (4) 360-390
    CrossrefPubMedGoogle Scholar
  • 16 Wall KM, Kilembe W, Vwalika B , et al. Hormonal contraception does not increase women's HIV acquisition risk in Zambian discordant couples, 1994-2012. Contraception 2015; 91 (6) 480-487
    CrossrefPubMedGoogle Scholar
  • 17 Grabowski M, Wawer M, Makumbi F. Injectable Hormonal Contraception Use and Women's Risk for HSV-2 Acquisition. CROI; February 23–26, 2015; Seattle, WA
    PubMedGoogle Scholar
  • 18 Huijbregts RP, Helton ES, Michel KG , et al. Hormonal contraception and HIV-1 infection: medroxyprogesterone acetate suppresses innate and adaptive immune mechanisms. Endocrinology 2013; 154 (3) 1282-1295
    CrossrefPubMedGoogle Scholar
  • 19 Chandra N, Thurman AR, Anderson S , et al. Depot medroxyprogesterone acetate increases immune cell numbers and activation markers in human vaginal mucosal tissues. AIDS Res Hum Retroviruses 2013; 29 (3) 592-601
    CrossrefPubMedGoogle Scholar
  • 20 Africander D, Louw R, Verhoog N, Noeth D, Hapgood JP. Differential regulation of endogenous pro-inflammatory cytokine genes by medroxyprogesterone acetate and norethisterone acetate in cell lines of the female genital tract. Contraception 2011; 84 (4) 423-435
    CrossrefPubMedGoogle Scholar
  • 21 Shanmugasundaram U, Critchfield JW, Pannell J , et al. Phenotype and functionality of CD4+ and CD8+ T cells in the upper reproductive tract of healthy premenopausal women. Am J Reprod Immunol 2014; 71 (2) 95-108
    CrossrefPubMedGoogle Scholar
  • 22 Myer L, Wright Jr TC, Denny L, Kuhn L. Nested case-control study of cervical mucosal lesions, ectopy, and incident HIV infection among women in Cape Town, South Africa. Sex Transm Dis 2006; 33 (11) 683-687
    CrossrefPubMedGoogle Scholar
  • 23 World Health Organization. Hormonal Contraceptive Methods for Women at High Risk of HIV and Living with HIV. Geneva: 2014
    Google Scholar
  • 24 Colvin CJ, Harrison A. Broadening the debate over HIV and hormonal contraception. Lancet Infect Dis 2015; 15 (2) 135-136
    CrossrefPubMedGoogle Scholar
  • 25 Ralph LJ, McCoy SI, Hallett T, Padian N. Next steps for research on hormonal contraception and HIV. Lancet 2013; 382 (9903) 1467-1469
    CrossrefPubMedGoogle Scholar
  • 26 Lavreys L, Baeten JM, Martin Jr HL , et al. Hormonal contraception and risk of HIV-1 acquisition: results of a 10-year prospective study. AIDS 2004; 18 (4) 695-697
    CrossrefPubMedGoogle Scholar
  • 27 Morrison CS, Turner AN, Jones LB. Highly effective contraception and acquisition of HIV and other sexually transmitted infections. Best Pract Res Clin Obstet Gynaecol 2009; 23 (2) 263-284
    CrossrefPubMedGoogle Scholar
  • 28 Achilles SL, Creinin MD, Stoner KA, Chen BA, Meyn L, Hillier SL. Changes in genital tract immune cell populations after initiation of intrauterine contraception. Am J Obstet Gynecol 2014; 211 (5) 489.e1-489.e9
    CrossrefPubMedGoogle Scholar
  • 29 Sciaranghella G, Wang C, Hu H , et al. CCR5 expression levels in HIV-uninfected women receiving hormonal contraception. J Infect Dis 2015; 212 (9) 1397-1401
    CrossrefPubMedGoogle Scholar
  • 30 Goldfien GA, Barragan F, Chen J , et al. Progestin-containing contraceptives alter expression of host defense-related genes of the endometrium and cervix. Reprod Sci 2015; 22 (7) 814-828
    CrossrefPubMedGoogle Scholar
  • 31 Sheffield JS, Wendel Jr GD, McIntire DD, Norgard MV. The effect of progesterone levels and pregnancy on HIV-1 coreceptor expression. Reprod Sci 2009; 16 (1) 20-31
    CrossrefPubMedGoogle Scholar
  • 32 Mugo NR, Heffron R, Donnell D , et al; Partners in Prevention HSV/HIV Transmission Study Team. Increased risk of HIV-1 transmission in pregnancy: a prospective study among African HIV-1-serodiscordant couples. AIDS 2011; 25 (15) 1887-1895
    CrossrefPubMedGoogle Scholar
  • 33 Gray RH, Li X, Kigozi G , et al. Increased risk of incident HIV during pregnancy in Rakai, Uganda: a prospective study. Lancet 2005; 366 (9492) 1182-1188
    CrossrefPubMedGoogle Scholar
  • 34 Morrison CS, Wang J, Van Der Pol B, Padian N, Salata RA, Richardson BA. Pregnancy and the risk of HIV-1 acquisition among women in Uganda and Zimbabwe. AIDS 2007; 21 (8) 1027-1034
    CrossrefPubMedGoogle Scholar
  • 35 Baeten JM, Donnell D, Ndase P , et al; Partners PrEP Study Team. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. N Engl J Med 2012; 367 (5) 399-410
    CrossrefPubMedGoogle Scholar
  • 36 Thigpen MC, Kebaabetswe PM, Paxton LA , et al; TDF2 Study Group. Antiretroviral preexposure prophylaxis for heterosexual HIV transmission in Botswana. N Engl J Med 2012; 367 (5) 423-434
    CrossrefPubMedGoogle Scholar
  • 37 Saag MS. Preventing HIV in women—still trying to find their VOICE. N Engl J Med 2015; 372 (6) 564-566
    CrossrefPubMedGoogle Scholar
  • 38 Trezza CR, Kashuba AD. Pharmacokinetics of antiretrovirals in genital secretions and anatomic sites of HIV transmission: implications for HIV prevention. Clin Pharmacokinet 2014; 53 (7) 611-624
    CrossrefPubMedGoogle Scholar
  • 39 Center for Disease Control and Prevention. Pre-Exposure Prophylaxis for the Prevention of HIV Infection in the United States—2014: A Clinical Practice Guideline. Atlanta, GA: 2014
    Google Scholar
  • 40 Grant RM, Liegler T, Defechereux P , et al. Drug resistance and plasma viral RNA level after ineffective use of oral pre-exposure prophylaxis in women. AIDS 2015; 29 (3) 331-337
    CrossrefPubMedGoogle Scholar
  • 41 Reliquet V, Winer N, Chereau N , et al. The spectrum of HIV mother-to-child transmission risk. J Int AIDS Soc 2014; 17 (4) (Suppl. 03) 19703
    PubMedGoogle Scholar
  • 42 World Health Organization. Guideline on When to Start Antiretroviral Therapy and on Pre-exposure Prophylaxis for HIV. Geneva; 2015; Available at http://www.who.int/hiv/pub/guidelines/earlyrelease-arv/en/ . Accessed October 13, 2015
    PubMedGoogle Scholar
  • 43 Perry SH, Swamy P, Preidis GA, Mwanyumba A, Motsa N, Sarero HN. Implementing the Jadelle implant for women living with HIV in a resource-limited setting: concerns for drug interactions leading to unintended pregnancies. AIDS 2014; 28 (5) 791-793
    CrossrefPubMedGoogle Scholar
  • 44 Leticee N, Viard JP, Yamgnane A, Karmochkine M, Benachi A. Contraceptive failure of etonogestrel implant in patients treated with antiretrovirals including efavirenz. Contraception 2012; 85 (4) 425-427
    CrossrefPubMedGoogle Scholar
  • 45 Landolt NK, Phanuphak N, Ubolyam S , et al. Significant decrease of ethinylestradiol with nevirapine, and of etonogestrel with efavirenz in HIV-positive women. J Acquir Immune Defic Syndr 2014; 66 (2) e50-e52
    PubMedGoogle Scholar
  • 46 Matiluko AA, Soundararjan L, Hogston P. Early contraceptive failure of Implanon in an HIV-seropositive patient on triple antiretroviral therapy with zidovudine, lamivudine and efavirenz. J Fam Plann Reprod Health Care 2007; 33 (4) 277-278
    CrossrefPubMedGoogle Scholar
  • 47 McCarty EJ, Keane H, Quinn K, Quah S. Implanon® failure in an HIV-positive woman on antiretroviral therapy resulting in two ectopic pregnancies. Int J STD AIDS 2011; 22 (7) 413-414
    CrossrefPubMedGoogle Scholar
  • 48 Murnane PM, Heffron R, Ronald A , et al; Partners PrEP Study Team. Pre-exposure prophylaxis for HIV-1 prevention does not diminish the pregnancy prevention effectiveness of hormonal contraception. AIDS 2014; 28 (12) 1825-1830
    CrossrefPubMedGoogle Scholar
  • 49 Todd CS, Deese J, Wang M , et al; FEM-PrEP Study Group. Sino-implant (II)® continuation and effect of concomitant tenofovir disoproxil fumarate-emtricitabine use on plasma levonorgestrel concentrations among women in Bondo, Kenya. Contraception 2015; 91 (3) 248-252
    CrossrefPubMedGoogle Scholar
  • 50 Heffron R, Mugo N, Were E , et al; Partners PrEP Study Team. Preexposure prophylaxis is efficacious for HIV-1 prevention among women using depot medroxyprogesterone acetate for contraception. AIDS 2014; 28 (18) 2771-2776
    CrossrefPubMedGoogle Scholar
  • 51 Abdool Karim Q, Abdool Karim SS, Frohlich JA , et al; CAPRISA 004 Trial Group. Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women. Science 2010; 329 (5996) 1168-1174
    CrossrefPubMedGoogle Scholar
  • 52 Abdool Karim SS, Abdool Karim Q, Kharsany AB , et al; CAPRISA 004 Trial Group. Tenofovir gel for the prevention of herpes simplex virus type 2 infection. N Engl J Med 2015; 373 (6) 530-539
    CrossrefPubMedGoogle Scholar
  • 53 The Lancet HIV. Antiretroviral gels: facing the FACTS. Lancet HIV 2015; 2 (4) e115
    PubMedGoogle Scholar
  • 54 Seidman D, Weber S, Aaron E, Cohan D, Grant R. The FACTS about women and pre-exposure prophylaxis. Lancet HIV 2015; 2 (6) e228
    PubMedGoogle Scholar
  • 55 Clinicaltrials Gov. National Institute of Health. Clinicaltrials Gov 2015
    PubMedGoogle Scholar
  • 56 The MPT Pipeline by Indication Combination . 2015; Available at: http://www.cami-health.org/documents/MPT-Pipeline-Table.pdf . Accessed September 30, 2015
    PubMed
  • 57 Manning J, Brown G, Vogelsong K, Kildebeck M, Zwerski S, Blithe D. Challenges and opportunities in funding the development and introduction of multipurpose prevention technologies. BJOG 2014; 121 (Suppl. 05) 12-14
    PubMedGoogle Scholar
  • 58 Rees H, Forbes A. Policy implications for multipurpose prevention technologies service delivery. BJOG 2014; 121 (Suppl. 05) 19-22
    PubMedGoogle Scholar
  • 59 Romano JW, Van Damme L, Hillier S. The future of multipurpose prevention technology product strategies: understanding the market in parallel with product development. BJOG 2014; 121 (Suppl. 05) 15-18
    PubMedGoogle Scholar
  • 60 MPT Product Development Database . Available at: http://mpts101.org/mpt-database . Accessed October 5, 2015
    PubMed
  • 61 Warren M. Condoms: the multipurpose prevention technologies that already exist. BJOG 2014; 121 (Suppl. 05) 9-11
    PubMedGoogle Scholar
  • 62 Eaton EF, Hoesley CJ. Barrier methods for human immunodeficiency virus prevention. Infect Dis Clin North Am 2014; 28 (4) 585-599
    CrossrefPubMedGoogle Scholar
  • 63 Origami Condoms Reinvented . Available at: http://www.origamicondoms.com/-!female-condom/cxt7 . Accessed October 4, 2015
    PubMed
  • 64 Schwartz JL, Weiner DH, Lai JJ , et al. Contraceptive efficacy, safety, fit, and acceptability of a single-size diaphragm developed with end-user input. Obstet Gynecol 2015; 125 (4) 895-903
    CrossrefPubMedGoogle Scholar
  • 65 Major I, Boyd P, Kilbourne-Brook M, Saxon G, Cohen J, Malcolm RK. A modified SILCS contraceptive diaphragm for long-term controlled release of the HIV microbicide dapivirine. Contraception 2013; 88 (1) 58-66
    CrossrefPubMedGoogle Scholar
  • 66 Smith-McCune K, Chen JC, Greenblatt RM , et al. Unexpected inflammatory effects of intravaginal gels (Universal Placebo Gel and Nonoxynol-9) on the upper female reproductive tract: a randomized crossover study. PLoS ONE 2015; 10 (7) e0129769
    CrossrefPubMedGoogle Scholar
  • 67 Fichorova RN, Tucker LD, Anderson DJ. The molecular basis of nonoxynol-9-induced vaginal inflammation and its possible relevance to human immunodeficiency virus type 1 transmission. J Infect Dis 2001; 184 (4) 418-428
    CrossrefPubMedGoogle Scholar
  • 68 Van Damme L, Ramjee G, Alary M , et al; COL-1492 Study Group. Effectiveness of COL-1492, a nonoxynol-9 vaginal gel, on HIV-1 transmission in female sex workers: a randomised controlled trial. Lancet 2002; 360 (9338) 971-977
    CrossrefPubMedGoogle Scholar
  • 69 Mesquita PM, Wilson SS, Manlow P , et al. Candidate microbicide PPCM blocks human immunodeficiency virus type 1 infection in cell and tissue cultures and prevents genital herpes in a murine model. J Virol 2008; 82 (13) 6576-6584
    CrossrefPubMedGoogle Scholar
  • 70 Bayer LL, Jensen JT. ACIDFORM: a review of the evidence. Contraception 2014; 90 (1) 11-18
    CrossrefPubMedGoogle Scholar
  • 71 Stone A. Multipurpose prevention technologies for reproductive and sexual health. Reprod Health Matters 2014; 22 (44) 213-217
    CrossrefPubMedGoogle Scholar
  • 72 Thurman AR, Clark MR, Hurlburt JA, Doncel GF. Intravaginal rings as delivery systems for microbicides and multipurpose prevention technologies. Int J Womens Health 2013; 5: 695-708
    PubMedGoogle Scholar
  • 73 Clark JT, Clark MR, Shelke NB , et al. Engineering a segmented dual-reservoir polyurethane intravaginal ring for simultaneous prevention of HIV transmission and unwanted pregnancy. PLoS ONE 2014; 9 (3) e88509
    CrossrefPubMedGoogle Scholar
  • 74 Ugaonkar SR, Wesenberg A, Wilk J , et al. A novel intravaginal ring to prevent HIV-1, HSV-2, HPV, and unintended pregnancy. J Control Release 2015; 213: 57-68
    CrossrefPubMedGoogle Scholar
  • 75 Woodsong C, Musara P, Chandipwisa A , et al. Interest in multipurpose prevention of HIV and pregnancy: perspectives of women, men, health professionals and community stakeholders in two vaginal gel studies in southern Africa. BJOG 2014; 121 (Suppl. 05) 45-52
    PubMedGoogle Scholar
  • 76 Ross J, Stover J. Use of modern contraception increases when more methods become available: analysis of evidence from 1982-2009. Glob Health Sci Pract 2013; 1 (2) 203-212
    PubMedGoogle Scholar
  • 77 Patel P, Borkowf CB, Brooks JT, Lasry A, Lansky A, Mermin J. Estimating per-act HIV transmission risk: a systematic review. AIDS 2014; 28 (10) 1509-1519
    CrossrefPubMedGoogle Scholar
  • 78 Supervie V, Viard JP, Costagliola D, Breban R. Heterosexual risk of HIV transmission per sexual act under combined antiretroviral therapy: systematic review and bayesian modeling. Clin Infect Dis 2014; 59 (1) 115-122
    CrossrefPubMedGoogle Scholar
  • 79 Cardo DM, Culver DH, Ciesielski CA , et al; Centers for Disease Control and Prevention Needlestick Surveillance Group. A case-control study of HIV seroconversion in health care workers after percutaneous exposure. N Engl J Med 1997; 337 (21) 1485-1490
    CrossrefPubMedGoogle Scholar
  • 80 Smith DK, Grohskopf LA, Black RJ , et al; U.S. Department of Health and Human Services. Antiretroviral postexposure prophylaxis after sexual, injection-drug use, or other nonoccupational exposure to HIV in the United States: recommendations from the U.S. Department of Health and Human Services. MMWR Recomm Rep 2005; 54 (RR-2): 1-20
    PubMedGoogle Scholar