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Current Obstetrics and Gynecology Reports

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01-03-2015 | Family Planning (A Burke, Section Editor)

Current Status of Multipurpose Prevention Technology (MPT) Development

Authors: Cynthia Woodsong, Jonathon Holt, Brid Devlin, Zeda Rosenberg

Published in: Current Obstetrics and Gynecology Reports | Issue 1/2015

Abstract

Multipurpose prevention technologies (MPTs) are pharmaceutical products being developed for multiple indications, primarily prevention of HIV, pregnancy, and/or sexually transmitted infections. MPT products could be a combination of multiple drugs co-formulated for separate indications, or a single product with multiple indications. This paper reviews MPT work published since 2013, including technical papers on aspects of product development, papers focused on issues that will be critical to future MPT clinical research and introduction, and selected papers concerning products for prevention of pregnancy or HIV/STIs. Collaborative efforts between researchers and funders aim to provide efficiencies in the product development process, building on experiences from both the contraceptive and vaginal microbicide fields.

1.•

Higgins JA, Smith NK, Sanders SA, Schick V, Herbenick D, Reece M, et al. Dual method use at last sexual encounter: a nationally representative, episode-level analysis of US men and women. Contracept. 2014;90(4):399–406. doi:10.1016/j.contraception.2014.06.003. For some time, use of two methods for prevention of pregnancy and HIV (e.g., condoms and contraceptives), or one method (condom) for both indications, has been reported as difficult to achieve, and this article presents new data from the US providing additional insights into the nature of these problems. The main problems observed were correct and consistent condom use, and the authors call for greater involvement of the male partner when condoms are used as a contraceptive method.CrossRef

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3.••

Harrison PF, Hemmerling A, Romano J, Whaley KJ, Holt BY. Developing multipurpose reproductive health technologies: an integrated strategy. AIDS Res Treat. 2013;2013:790154. doi:10.1155/2013/790154. Harrison et al. provided a succinct summary of MPT development efforts. This paper is an essential “go-to” for anyone interested in MPTs. The paper includes a number of tables with important details about MPT development, including a table summarizing the regional needs and priorities for MPTs.

4.••

Lusti-Narasimhan M, ed. Multipurpose Prevention Technologies: Maximising Positive Synergies Br J Obstet Gynaec. 2014;121, Suppl. 5. This special issue of BJOG includes “editorials, commentaries, review articles and original research focussing on the current progress in developing and promoting multipurpose prevention technologies.” There are 16 articles in the issue, which together provide a comprehensive overview of MPT development efforts.

5.•

Holt BY, Manning J, Hemmerling A, Shields W, Vyda L, Lusti-Narasimhang M. Ensuring successful development and introduction of multipurpose prevention technologies through an innovative partnership approach. Br J Obstet Gynaec. 2014;S5:3–8. Holt et al. , provided a summary of the collaborative efforts to promote MPT development. In addition to providing useful information on the MPT field, the paper provided a case example of how research and development partnerships could contribute to public health.CrossRef

Friend DR, Clark JT, Kiser PF, Clark MR. Multipurpose prevention technologies: Products in development. Antiviral Res. 2013;100(Suppl):S39–47. doi:10.1016/j.antiviral.2013.09.030.CrossRefPubMed

Brady M, Manning J. Lessons from reproductive health to inform multipurpose prevention technologies: don't reinvent the wheel. Antiviral Res. 2013;100(Suppl):S25–31. doi:10.1016/j.antiviral.2013.09.019.CrossRefPubMed

Lusti-Narasimhan M, Merialdi M, Holt BY. Advancing the sexual and reproductive health and human rights of women beyond 2015. Br J Obstet Gynaec. 2014;121(3):251. doi:10.1111/1471-0528.12606.CrossRef

Malcolm RK, Fetherston SM. Delivering on MPTs: addressing the needs, rising to the challenges and making the opportunities. Contracept. 2013;88(3):321–5. doi:10.1016/j.contraception.2013.06.009.CrossRef

10.

Manning JBG, Vodelsong K, et al. Challenges and opportunities in funding multipurpose prevention technologies: development and introduction. Brit J Obstet Gynaec. 2014;S5:12–4.CrossRef

11.

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14.

Woodsong C, McGrory E, Farley T. Preparing for microbicide introduction, rollout, and sustained access. In: Nuttall J, editor. Microbicides for Prevention of HIV Infection. Curr Top Microbiol Immun. Berlin: Springer; 2014. p. p. 153–75.CrossRef

15.•

Woodsong C, Musara P, Chandipwisa A, Montgomery E, Alleman P, Chirenje M, 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. Br J Obstet Gynaec. 2014;S5:45–52. This article presented primary data on MPT acceptability and assumptions of potential users, health professionals, and community leaders in two African countries. These data, collected in two HIV-prevention microbicide gel studies, indicated strong interest in MPTs.CrossRef

16.•

Whaley KJ, Zeitlin L. Antibody-based concepts for multipurpose prevention technologies. Antiviral Res. 2013;100:S48–53. doi:10.1016/j.antiviral.2013.09.027. Whaley and Zeitlin provided an overview of studies investigating the potential for antibody- based MPTs, and discussed related issues of antibody evasion and resistance. The article also included a discussion of manufacturing and regulatory considerations for antibody-based MPTs.CrossRefPubMedCentralPubMed

17.•

Tolley EE, Morrow KM, Owen DH. Designing a multipurpose technology for acceptability and adherence. Antiviral Res. 2013;100:S54–9. doi:10.1016/j.antiviral.2013.09.029. Tolley et al., summarized approaches to conduct social and behavioral science research to provide results relevant to MPT product development, including sensory perception research and methodologies to determine preferences for specific product attributes.CrossRefPubMed

18.

Gengiah TN, Mansoor LE, Upfold M, Naidoo A, Yende-Zuma N, Kashuba AD, et al. Measuring adherence by visual inspection of returned empty gel applicators in the CAPRISA 004 microbicide trial. AIDS Behav. 2014;18(5):820–5. doi:10.1007/s10461-014-0749-4.CrossRefPubMed

19.

Morey TE, Wasdo S, Wishin J, Quinn B, van der Straten A, Booth M, et al. Feasibility of a breath test for monitoring adherence to vaginal administration of antiretroviral microbicide gels. J Clin Pharmacol. 2013;53(1):103–11. doi:10.1177/0091270011434157.CrossRefPubMed

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Guttmacher Institute. Unplanned pregnancy common worldwide - neither legal status of abortion or health risks deters women from terminating pregnancies. Press Release: The Alan Guttmacher Institute 2014

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Darroch JE, Singh S. Trends in contraceptive need and use in developing countries in 2003, 2008, and 2012: an analysis of national surveys. Lancet. 2013;381(9879):1756–62. doi:10.1016/S0140-6736(13)60597-8.CrossRefPubMed

23.

Calvert C, Ronsmans C. The contribution of HIV to pregnancy-related mortality: a systematic review and meta-analysis. AIDS. 2013. doi:10.1097/QAD.0b013e32835fd940.PubMedCentralPubMed

24.•

ESHRE Capri Workshop Group. Simultaneous prevention of unintended pregnancy and STIs: a challenging compromise. Hum Reprod Update. 2014;20(6):952–63. This paper reviewed epidemiological data from the European region that demonstrated the need for MPTs. The authors noted that sources for relevant data are more readily available for developing countries, yet the European data indicated a strong need for MPTs in this region. The methodology and types of data sources could be applied to assessment of need in other regions.

25.

Egarter C, Tirri BF, Bitzer J, Kaminskyy V, Oddens BJ, Prilepskaya V, et al. Women’s perceptions and reasons for choosing the pill, patch, or ring in the CHOICE study: a cross-sectional survey of contraceptive method selection after counseling. BMC Women's Health. 2013;13(1):9.CrossRefPubMedCentralPubMed

26.

Jones HE. Time to focus on improving the contraceptive method mix in high HIV prevalence settings and let go of unanswerable questions. Contracept. 2014;90(4):357–9. doi:10.1016/j.contraception.2014.05.014.CrossRef

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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):203–12.

28.

Smit JA, Beksinska ME. Hormonal contraceptive continuation and switching in South Africa: implications for evaluating the association of injectable hormonal contraceptive use and HIV. J Acquir Immune Defic Syndr. 2013;62(3):363–5. doi:10.1097/QAI.0b013e31827e818a.CrossRefPubMed

29.

Phillips S, Steyn P. Temmerman M. Best Practice Res Clin Obstet Gynaec: Contraceptive options for women living with HIV; 2014.

30.

Romano J, Manning J, Hemmerling A, McGrory E, Holt BY. Prioritizing multipurpose prevention technology development and investments using a target product profile. Antiviral Res. 2013;100(Suppl):S32–8. doi:10.1016/j.antiviral.2013.09.016.CrossRefPubMed

31.•

Polis CB, Westreich D, Balkus JE, Heffron R. Assessing the effect of hormonal contraception on HIV acquisition in observational data: challenges and recommended analytic approaches. AIDS. 2013;27:S35–43. This paper is one of several by Polis and colleagues to consider the evidence linking hormonal contraceptives with HIV acquisition and disease progression. The paper included a careful review of available data, and concluded that although oral contraceptive methods in general do not indicate an increased risk, the evidence for some contraceptive methods was less certain.CrossRefPubMedCentralPubMed

32.

World Health Organization. Hormonal contraception and HIV technical statement. 2012.Geneva, Switzerland: World Health Organization. WHO Reference No.: WHO/RHR/12.08.

33.

Westhoff CL, Winikoff B. DMPA and HIV: do we need a trial? Contracept. 2014;90(4):353. doi:10.1016/j.contraception.2014.08.008.CrossRef

34.

Butler AR, Smith JA, Polis CB, Gregson S, Stanton D, Hallett TB. Modelling the global competing risks of a potential interaction between injectable hormonal contraception and HIV risk. AIDS. 2013;27(1):105–13. doi:10.1097/QAD.0b013e32835a5a52.CrossRefPubMed

35.

Crook AM, Ford D, Gafos M, Hayes R, Kamali A, Kapiga S, et al. Injectable and oral contraceptives and risk of HIV acquisition in women: an analysis of data from the MDP301 trial. Hum Reprod. 2014;29(8):1810–7. doi:10.1093/humrep/deu113.CrossRefPubMedCentralPubMed

36.

Murnane PM, Heffron R, Ronald A, Bukusi EA, Donnell D, Mugo NR, et al. Pre-exposure prophylaxis for HIV-1 prevention does not diminish the pregnancy prevention effectiveness of hormonal contraception. AIDS. 2014;28(12):1825–30. doi:10.1097/QAD.0000000000000290.CrossRefPubMed

37.

Achilles SL, Hillier SL. The complexity of contraceptives: understanding their impact on genital immune cells and vaginal microbiota. AIDS. 2013;27:S5–15.CrossRefPubMedCentralPubMed

38.

van de Wijgert JH, Verwijs MC, Turner AN, Morrison CS. Oral and injectable hormonal contraception decrease risk of bacterial vaginosis but oral contraception may increase risk of vaginal candidiasis: a systematic review of published and unpublished data. Sex Transm Infect. 2013;89 Suppl 1:A217. doi:10.1136/sextrans-2013-051184.0678.CrossRef

39.

Mwaura M, Hardy L, Delany-Moretlwe S, Ndayisaba G, Mandaliya K, Verhelst R, et al. P3.060 There is a need for multipurpose prevention technologies targeting hiv and common reproductive tract infections: data from the microbicide safety biomarkers study team. Sex Transm Infect. 2013;89 Suppl 1:A166–7. doi:10.1136/sextrans-2013-051184.0520.CrossRef

40.•

Brady MM, Tolley E. Aligning product development and user perspectives: social-behavioural dimensions of multipurpose prevention technologies. Br J Obstet Gynaec. 2014;S5:70–8. Work on a Target Product Profile for MPTs has been criticized for giving inadequate attention to social and behavioral science aspects. In this article, the authors provided tables for different types of MPT dosage forms and examples of product considerations that are expected to be of importance to end users.CrossRef

41.•

Merkatz RB, Plagianos M, Hoskin E, Cooney M, Hewett PC, Mensch BS. Acceptability of the nestorone(R)/ethinyl estradiol contraceptive vaginal ring: development of a model; implications for introduction. Contracept. 2014;90(5):514–21. doi:10.1016/j.contraception.2014.05.015. This publication presented a conceptual model linking contraceptive vaginal ring acceptability and adherence. Merkatz et al., presented four key domains associated with product use that were assessed in questionnaires with trial participants in Latin America, US, Europe, and Australia. The model will likely prove useful for future investigations of MPT acceptability, and could inform product design decisions as well as introduction efforts.CrossRef

42.

Abdool Karim Q, Abdool Karim SS, Frohlich JA, Grobler AC, Baxter C, Mansoor LE, et al. Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women. Science. 2010;329(5996):1168–74.CrossRefPubMedCentralPubMed

43.•

FACTS. FACTS 001 Design. http://factsconsortium.wordpress.com/facts-001-study/facts-001-study-design/. Accessed 10 Oct 2014. Results from the FACTS 001 trial of tenofovir gel are not available at the time of this writing. However, these results could demonstrate efficacy of a vaginal gel for prevention of HIV and HSV, and thus, the FACTS website will be an important site to watch for trial results and MPT implications.

44.•

Devlin B, Nuttall J, Wilder S, Woodsong C, Rosenberg Z. Development of dapivirine vaginal ring for HIV prevention. Antiviral Res. 2013;100:S3–8. doi:10.1016/j.antiviral.2013.09.025. Devlin et al., reviewed the range of activities contributing to development of the vaginal ring currently being tested in two Phase III HIV-prevention microbicide trials. Discussion included selection of dapivirine as the API , and development of the platinum-catalyzed silicone elastomer matrix ring configuration.CrossRefPubMed

45.

Ramarao S, Clark H, Merkatz R, Sussman H, Sitruk-Ware R. Progesterone vaginal ring: introducing a contraceptive to meet the needs of breastfeeding women. Contracept. 2013. doi:10.1016/ j.contraception.2013.05.004.

46.•

Kenney J, Rodriguez A, Kizima L, Seidor S, Menon R, Jean-Pierre N, et al. A modified zinc acetate gel, a potential nonantiretroviral microbicide, is safe and effective against simian-human immunodeficiency virus and herpes simplex virus 2 infection in vivo. Antimicrob Agents Chemother. 2013;57(8):4001–9. doi:10.1128/AAC.00796-13. Although the MPT priority indication is prevention of HIV and pregnancy, it is important to bear in mind that products to prevent HIV and herpes are also advancing in the pipeline. This article provided an overview of efforts to develop such a product.CrossRefPubMedCentralPubMed

47.

Malcolm RK, Fetherston SM, McCoy CF, Boyd P, Major I. Vaginal rings for delivery of HIV microbicides. Int J Women’s Health. 2012;4:595–605. doi:10.2147/IJWH.S36282.CrossRef

48.•

Fetherston SM, Boyd P, McCoy CF, McBride MC, Edwards K-L, Ampofo S, et al. A silicone elastomer vaginal ring for HIV prevention containing two microbicides with different mechanisms of action. Eur J Pharm Sci. 2013;48(3):406–15. doi:10.1016/j.ejps.2012.12.002. This article provided information on technical considerations for a silicone elastomer vaginal ring for MPT delivery using a matrix design to deliver dapivirine and miraviroc. Although both of these drugs are intended for HIV prevention, aspects of the matrix ring design described here could be informative for a ring delivering an ARV and contraceptive.CrossRefPubMed

49.

Rohan LC, Devlin B, Yang H. Microbicide Dosage Forms. In: Nuttall J, editor. Microbicides for prevention of HIV infection. Curr Top in Microbiol Immunol. Berlin: Springer; 2014.

50.•

Clark JT, Clark MR, Shelke NB, Johnson TJ, Smith EM, Andreasen AK, 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. doi:10.1371/journal.pone.0088509.CrossRefPubMedCentralPubMed

51.•

Moss JA, Malone AM, Smith TJ, Kennedy S, Nguyen C, Vincent KL, et al. Pharmacokinetics of a multipurpose pod-intravaginal ring simultaneously delivering five drugs in an ovine model. Antimicrob Agents Chemother. 2013;57(8):3994–7. A vaginal ring using a “pod” design was described in this article. Such pods would contain an API, and combinations of pod types could be used for MPTs for various indications. The paper presented results of sheep studies using rings with five pods, and demonstrated “proof of principal” for the design.CrossRefPubMedCentralPubMed

52.

Thurman AR, Clark MR, Doncel GF. Multipurpose prevention technologies: biomedical tools to prevent HIV-1, HSV-2, and unintended pregnancies. Infect Dis Obstet Gynaec. 2011;2011:1–10.CrossRef

53.

Pentlicky S, Rosen M, Coffey PS, Kilbourne-Brook M, Shaunik A, Schreiber CA, et al. An exploratory, randomized, crossover MRI study of microbicide delivery with the SILCS diaphragm compared to a vaginal applicator. Contracept. 2013;87(2):187–92. doi:10.1016/j.contraception.2012.06.016.CrossRef

54.•

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. Contracept. 2013;88(1):58–66. doi:10.1016/j.contraception.2012.10.018. This paper reported on successful efforts to include the ARV dapivirine in a cervical barrier modeled on the SILCS diaphragm. Extensive details on the product design were provided, supporting the potential for this device to serve as an MPT dosage form.CrossRef

55.

Machado RM, Palmeira De Oliveira A, Martinez De Oliveira J, Palmeira De Oliveira R. Vaginal films for drug delivery. J Pharma Sci. 2013;102(7):2069–81.CrossRef

56.•

Blakney AK, Krogstad EA, Jiang YH, Woodrow KA. Delivery of multipurpose prevention drug combinations from electrospun nanofibers using composite microarchitectures. Int J Nanomedicine. 2014;9:2967. Blackney et al., provided an overview of technical considerations for development of electrospun nanofibers for MPT drug delivery. Although this technology is at an early stage of development, adherence problems observed with current delivery modes prompt interest in increasing the options for drug delivery.CrossRefPubMedCentralPubMed

57.

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58.

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60.•

Cohen JA, Mastroianni AC, Macklin R. Ethical issues for late-stage trials of multipurpose prevention technologies for HIV and pregnancy. Int J Gynaec Obstet. 2014. This important publication raised a number of ethics-related issues that have not been widely discussed in MPT development. These include selection of study populations, standard of case and ancillary care offered to participants. The authors pointed out that as MPT efforts advance to testing in clinical trials, the trial protocols must adequately address these issues.

61.

IPM. IPM Annual Report 2013. 2013. Silver Spring, MD: International Partnership for Microbicides. http://www.ipmglobal.org/publications/2013-ipm-annual-report-responding-women%E2%80%99s-needs. Accessed 10 Oct 2014.

Title: Current Status of Multipurpose Prevention Technology (MPT) Development
Authors: Cynthia Woodsong
Jonathon Holt
Brid Devlin
Zeda Rosenberg
Publication date: 01-03-2015
Publisher: Springer US
Published in: Current Obstetrics and Gynecology Reports / Issue 1/2015
Electronic ISSN: 2161-3303
DOI: https://doi.org/10.1007/s13669-014-0107-6

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Current Status of Multipurpose Prevention Technology (MPT) Development

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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