Women worldwide confront two frequently concurrent reproductive health challenges: the need for contraception and for protection from sexually transmitted infections, importantly HIV/AIDS. While conception and infection share the same anatomical site and mode of transmission, there are no reproductive health technologies to date that simultaneously address that reality. Relevant available technologies are either contraceptive or anti-infective, are limited in number, and require different modes of administration and management. These “single-indication” technologies do not therefore fully respond to what is a substantial reproductive health need intimately linked to pivotal events in many women's lives. This paper reviews an integrated attempt to develop multipurpose prevention technologies—“MPTs”—products explicitly designed to simultaneously address the need for both contraception and protection from sexually transmitted infections. It describes an innovative and iterative MPT product development strategy with the following components: identifying different needs for such technologies and global variations in reproductive health priorities, defining “Target Product Profiles” as the framework for a research and development “roadmap,” collating an integrated MPT pipeline and characterizing significant pipeline gaps, exploring anticipated regulatory requirements, prioritizing candidates for problem-solving and resource investments, and implementing an ancillary advocacy agenda to support this breadth of effort. 1. Introduction The combined burden of maternal and infant mortality and morbidity produced by unintended pregnancies and sexually transmitted infections—individually and as a consequence of their multiple interactions—is compelling in its volume, extent, and complexity. For an array of behavioral, biological, physiological, and sociocultural and political reasons, most of that burden falls on women in developing countries. In those countries, of the 80 million unintended pregnancies estimated for 2012, 63 million will occur among the 222 million women defined as having an “unmet need” for modern contraception [1]. Those unintended pregnancies will, in turn, result in 30 million unplanned births; 10 million miscarriages, including stillbirths; and 40 million abortions, of which one-third to one-half will be unsafe. Women aged 15–19 are at particular risk of these events [2]. Sexually transmitted infections (STIs) further compound these burdens, with which they are relentlessly intertwined. The World Health Organization estimates that 448 million
References
[1]
J. E. Darroch and S. Singh, Estimating Unintended Pregnancies Averted by Couple-Years of Protection (CYP), Guttmacher Institute, New York, NY, USA, 2011.
[2]
S. Singh and J. E. Darroch, “Adding It Up: The Costs and Benefits of Investing in Family Planning and Maternal and Newborn Health. Guttmacher Institute and United Nations Population Fund (UNFPA),” 2009, http://www.guttmacher.org/pubs/AIU-2012-estimates.pdf.
[3]
World Health Organization, “Sexually transmitted infections: Fact Sheet No. 110,” 2011, http://www.who.int/mediacentre/factsheets/fs110/en/.
[4]
K. J. Looker, G. P. Garnett, and G. P. Schmid, “An estimate of the global prevalence and incidence of herpes simplex virus type 2 infection,” Bulletin of the World Health Organization, vol. 86, no. 10, pp. 805–812, 2008.
[5]
WHO/ICO Information Centre on HPV and Cervical Cancer (HPV Information Centre), “Human Papillomavirus and Related Cancers in World. Summary Report 2010,” 2010, http://hpv2010.org/main/images/stories/docs/HPVInformationCentre_SummaryReportWorld_Feb2010.pdf.
[6]
D. T. Fleming and J. N. Wasserheit, “From epidemiological synergy to public health policy and practice: the contribution of other sexually transmitted diseases to sexual transmission of HIV infection,” Sexually Transmitted Infections, vol. 75, no. 1, pp. 3–17, 1999.
[7]
Cohen and MS, “Classical sexually transmitted diseases drive the spread of HIV-1: back to the future,” The Journal of Infectious Diseases, vol. 206, no. 1, pp. 1–2, 2012.
[8]
J. Stover, L. Dougherty, and M. Hamilton, “Are Cost Savings Incurred by Offering Family Planning at Emergency Plan HIV/AIDS Care and Treatment Facilities?” Futures Group/POLICY Project, Washington, DC, USA, 2006, http://www.policyproject.com/pubs/generalreport/FP-HIV%20Integration%20Costs%20and%20Savings%20Final.pdf.
[9]
A. Tong, P. Sainsbury, and J. Craig, “Consolidated criteria for reporting qualitative research (COREQ): a 32-item checklist for interviews and focus groups,” International Journal for Quality in Health Care, vol. 19, no. 6, pp. 349–357, 2007.
[10]
Population Council, “Facilitating Regulatory Approval of Multipurpose Prevention Technologies (MPTs) for Reproductive Health Day of Dialogue on Multipurpose Prevention Technologies: Toward Clarity in Nomenclature,” 2011, http://cami-health.org/documents/2011DayOfDialogueNomenclature_Report.pdf.
[11]
Coalition Advancing Multipurpose Innovations (CAMI), “Multipurpose Prevention Technologies for Reproductive Health: Advancing the Scientific and Product Development Agenda Report of a “Think Tank”,” 2011, http://www.cami-health.org/documents/050511-MPT-ThinkTank.pdf.
[12]
Coalition Advancing Multipurpose Innovations (CAMI), “Multipurpose Prevention Technologies for Reproductive Health 2011 Symposium,” 2011, http://cami-health.org/documents/MPT2011-Symposium-Report.pdf.
[13]
Coalition Advancing Multipurpose Innovations (CAMI), “Global Forum on Multipurpose Prevention Technologies for Reproductive Health,” 2011, http://cami-health.org/documents/2012-Global-Forum-Report.pdf.
[14]
K. Rawe, A. Dunford, J. Stewart, J. Espey, and J. Stoeckel, “Every Woman's Right. London: Save the Children UK,” 2012, http://www.savethechildren.org/atf/cf/%7B9def2ebe-10ae-432c-9bd0-df91d2eba74a%7D/EVERY_WOMANS_RIGHT_REPORT_JUNE_2012.PDF.
[15]
Population Reference Bureau, “World Population Data Sheet,” 2011, http://www.prb.org/pdf11/2011population-data-sheet_eng.pdf.
[16]
Guttmacher Institute and International Planned Parenthood Federation, “Facts on Satisfying the Need for Contraception in Developing Countries,” November 2010, http://www.imea.fr/imea-fournier/imea-fournier-2010/101122-c-Contraception-PVD.pdf.
[17]
ORC Macro, “Demographic and Health Surveys 2004–1010,” Calverton, Md, USA, 2013, http://www.measuredhs.com.
[18]
UNFPA, “Contraceptive Commodities for Women’s Health. Report for UN Commission on Lifesaving commodities for Women and Children,” 2012, http://www.unfpa.org/webdav/site/global/shared/images/publications/2012/UN%20Commission_%20FP%20Synthesis_%20Final%2019%20March%202012.pdf.
[19]
S. R. Schwartz, H. Rees, S. Mehta, W. D. Venter, T. E. Taha, and V. Black, “High incidence of unplanned pregnancy after antiretroviral therapy initiation: findings from a prospective cohort study in South Africa,” PLoS ONE, vol. 7, no. 4, Article ID e36039, 2012.
[20]
A. R. Butler, J. A. Smith, C. B. Polis, S. Gregson, D. Stanton, and T. B. Hallett, “Modelling the global competing risks of a potential interaction between injectable hormonal contraception and HIV risk,” AIDS, vol. 27, no. 1, pp. 105–113, 2013.
[21]
L. F. Johnson, R. E. Dorrington, D. Bradshaw, and D. J. Coetzee, “The effect of syndromic management interventions on the prevalence of sexually transmitted infections in South Africa,” Sexual and Reproductive Healthcare, vol. 2, no. 1, pp. 13–20, 2011.
[22]
WHO/ICO HPV Information Centre, “Human Papillomavirus and Related Cancers in Africa. Summary Report 2010. Table 1: Key statistics in Africa and its regions,” 2010.
[23]
C. R. Cohen, J. R. Lingappa, J. M. Baeten et al., “Bacterial vaginosis associated with increased risk of female-to-male HIV-1 transmission: a prospective cohort analysis among African couples,” PLoS Medicine, vol. 9, no. 6, Article ID e1001251, 2012.
[24]
L. Myer, L. Denny, R. Telerant, M. De Souza, T. C. Wright, and L. Kuhn, “Bacterial vaginosis and susceptibility to HIV infection in South African women: a nested case-control study,” Journal of Infectious Diseases, vol. 192, no. 8, pp. 1372–1380, 2005.
[25]
M. E. Thoma, R. H. Gray, N. Kiwanuka, M. C. Wang, N. Sewankambo, and M. J. Wawer, “The natural history of bacterial vaginosis diagnosed by gram stain among women in Rakai, Uganda,” Sexually Transmitted Diseases, vol. 38, no. 11, pp. 1040–1045, 2011.
[26]
R. Heffron, D. Donnell, H. Rees et al., “Use of hormonal contraceptives and risk of HIV-1 transmission: a prospective cohort study,” The Lancet Infectious Diseases, vol. 12, no. 1, pp. 19–26, 2012.
[27]
Office of Registrar General India, “Maternal & Child Mortality and Total Fertility Rates Sample Registration System (SRS),” 2011, http://censusindia.gov.in/vital_statistics/SRS_Bulletins/MMR_release_070711.pdf.
[28]
M. A. Koenig, R. Acharya, T. K. Roy, and S. Singh, “The Measurement of Unintended Pregnancy in Rural India: A Comparison of Prospective versus Retrospective Assessment,” Bloomberg School of Public Health, The Johns Hopkins University (USA) and International Institute for Population Sciences, Mumbai (India). Abstract at PAA 2005, http://paa2005.princeton.edu/download.aspx?submissionId=51322.
[29]
International Institute for Population Sciences (IIPS) and Macro International, “National Family Health Survey (NFHS-3), 2005–06: India: Volume I,” Mumbai: IIPS, 2007, http://www.measuredhs.com/pubs/pdf/FRIND3/FRIND3-Vol1AndVol2.pdf.
[30]
K. G. Santhya, R. Acharya, S. J. Jejeebhoy, and U. Ram, “Timing of first sex before marriage and its correlates: evidence from India,” Culture, Health and Sexuality, vol. 13, no. 3, pp. 327–341, 2011.
[31]
International Institute for Population Sciences (IIPS), “District Level Household and Facility Survey (DLHS-3), 2007-08: India,” Mumbai: IIPS, 2010, http://www.rchiips.org/pdf/INDIA_REPORT_DLHS-3.pdf.
[32]
AVERT, “India HIV & AIDS Statistics,” 2013, http://www.avert.org/india-hiv-aids-statistics.htm.
[33]
National Aids Control Organisation (NACO). Ministry Of Health and Family Welfare. Government of India, “HIV Sentinel Surveillance and HIV Estimation in India 2007. A Technical Brief,” 2008, http://nacoonline.org/upload/Publication/M&E%20Surveillance,%20Research/HIV%20Sentinel%20Surveillance%20and%20HIV%20Estimation%202007_A%20Technical%20Brief.pdf.
[34]
National Aids Control Organisation (NACO). Ministry Of Health and Family Welfare. Government of India, “National Aids Control Programme III. Report on Mid-Term Review of Sexually Transmitted Infection Services,” 2009, http://nacoonline.org/upload/STI%20RTI%20services/STI%20RTI%20MONOGRAPH%20_NACP-III-.pdf.
[35]
R. Will, “Contraceptive Use in China. US-China Today. University of Southern California US-China Institute,” 2012, http://www.uschina.usc.edu/w_usci/showarticle.aspx?articleID=18021&AspxAutoDetectCookieSupport=1.
[36]
Ministry of Health of the People's Republic of China, “2012 China AIDS Response Progress Report,” 2012, http://www.unaids.org/en/dataanalysis/monitoringcountryprogress/progressreports/2012countries/ce_CN_Narrative_Report[1].pdf.
[37]
UNGASS, “China 2010 UNGASS Country Progress Report (2008-2009),” 2010, http://data.unaids.org/pub/Report/2010/china_2010_country_progress_report_en.pdf.
[38]
X. Qian, S. Tang, and P. Garner, “Unintended pregnancy and induced abortion among unmarried women in China: a systematic review,” BMC Health Services Research, vol. 4, article 1, pp. 1–4, 2004.
[39]
X. Fang, Y. Zhou, Y. Yang, Y. Diao, and H. Li, “Prevalence and risk factors of trichomoniasis, bacterial vaginosis, and candidiasis for married women of child-bearing age in rural Shandong,” Japanese Journal of Infectious Diseases, vol. 60, no. 5, pp. 257–261, 2007.
[40]
C. Li, H. R. Han, J. E. Lee, M. Lee, Y. Lee, and M. T. Kim, “Knowledge, behaviors and prevalence of reproductive tract infections: a descriptive study on rural women in Hunchun, China,” Asian Nursing Research, vol. 4, no. 3, pp. 122–129, 2010.
[41]
X. J. Zhang, Q. Shen, G. Y. Wang et al., “Risk factors for reproductive tract infections among married women in rural areas of Anhui Province, China,” European Journal of Obstetrics Gynecology and Reproductive Biology, vol. 147, no. 2, pp. 187–191, 2009.
[42]
L. B. Finer and K. Kost, “Unintended Pregnancy Rates at the State Level,” Perspectives on Sexual and Reproductive Health, vol. 43, no. 2, pp. 78–87, 2011.
[43]
K. Kost, S. Henshaw, and L. Carlin, “U.S. Teenage Pregnancies, Births and Abortions: National and State Trends and Trends by Race and Ethnicity,” 2010, Guttmacher Institute, http://www.guttmacher.org/pubs/USTPtrends.pdf.
[44]
R. K. Jones and M. L. Kavanaugh, “Changes in abortion rates between 2000 and 2008 and lifetime incidence of abortion,” Obstetrics & Gynecology, vol. 117, no. 6, pp. 1358–1366, 2011.
[45]
L. B. Finer and M. R. Zolna, “Unintended pregnancy in the United States: incidence and disparities,” Contraception, vol. 85, no. 5, pp. 478–485, 2006.
[46]
K. Kost and S. Henshaw, “U.S. Teenage Pregnancy, Births, and Abortions, 2008: National Trends by Age, Race, and Ethnicity,” Guttmacher Institute, February 2012.
[47]
Centers for Disease Control and Prevention, “Chlamydia screening among sexually active young female enrollees of health plans-United States, 2000–2007,” Morbidity and Mortality Weekly Report, vol. 58, no. 14, pp. 362–365, 2009.
[48]
Centers for Disease Control and Prevention, “Genital herpes. CDC Fact Sheet,” December 2007, http://www.cdc.gov/std/Herpes/STDFact-Herpes.htm.
[49]
Centers for Disease Control and Prevention, “Trichomoniasis, CDC Fact Sheet,” December 2007, http://www.cdc.gov/std/trichomonas/STDFact-Trichomoniasis.htm.
[50]
Centers for Disease Control and Prevention, “Genital HPV infection. CDC Fact Sheet,” May 2004, http://www.cdc.gov/std/HPV/STDFact-HPV.htm.
[51]
Centers for Disease Control and Prevention, “HIV in the United States: At A Glance,” 2012http://www.cdc.gov/hiv/resources/factsheets/PDF/HIV_at_a_glance.pdf.
[52]
Centers for Disease Control and Prevention, Morbidity and Mortality Weekly Report, vol. 60, no. 31, 2011.
[53]
Centers for Disease Control and Prevention, “HIV/AIDS in the United States, CDC HIV/AIDS Facts,” 2008, http://www.cdc.gov/hiv/resources/factsheets/us.htm.
[54]
European Centre for Disease Prevention and Control, “Sexually Transmitted Infections in Europe, 1990–2009,” Stockholm: ECDC, 2011.
[55]
European Centre for Disease Prevention and Control/WHO Regional Office for Europe, “HIV/AIDS surveillance in Europe 2010,” Stockholm: ECDC, 2011.
[56]
P. W. Tebbey and C. Rink, “Target product profile: a renaissance for its definition and use,” Journal of Medical Marketing, vol. 9, no. 4, pp. 301–307, 2009.
[57]
A. Stone, “Advancing Prevention Technologies for Sexual and Reproductive Health,” Report of a 2009 Symposium in Berkeley, Calif, USA, http://cami-health.org/resources/reports.php.
[58]
US Food and Drug Administration (USFDA), Center for Drug Evaluation and Research, “Guidance for Industry and Review Staff: Target Product Profile-A Strategic Development Process Tool,” Draft Guidance, March 2007, http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm080593.pdf.
[59]
The Collaboration for AIDS Vaccine Discovery, “Topic 4 Overview: Passive Immunization with Human Monoclonal Antibodies for HIV Prevention. Diversifying the Pipeline of Product Concepts for an HIV Vaccine: RFP Overview and Guidelines,” Bill & Melinda Gates Foundation, 2010.
[60]
A. B. Balazs, J. Chen, C. M. Hong, D. S. Rao, L. Yang, and D. Baltimore, “Antibody-based protection against HIV infection by vectored immunoprophylaxis,” Nature, vol. 481, no. 7379, pp. 81–84, 2011.
[61]
U. M. Abdel-Motal, P. T. N. Sarkis, T. Han et al., “Anti-gp120 minibody gene transfer to female genital epithelial cells protects against HIV-1 virus challenge in vitro,” PLoS ONE, vol. 6, no. 10, Article ID e26473, 2011.
[62]
J. Mestecky, M. Raska, J. Novak, R. C. Alexander, and Z. Moldoveanu, “Antibody-mediated protection and the mucosal immune system of the genital tract: relevance to vaccine design,” Journal of Reproductive Immunology, vol. 85, no. 1, pp. 81–85, 2010.
[63]
D. R. Friend, “Drug delivery in multiple indication (multipurpose) prevention technologies: systems to prevent HIV-1 transmission and unintended pregnancies or HSV-2 transmission,” Expert Opinion on Drug Delivery, vol. 4, no. 9, pp. 417–427, 2012.
[64]
CONRAD, “Online information on current research efforts regarding MPTs,” 2013, http://www.conrad.org/research-technologies.html.
[65]
J. Kenney, R. Singer, N. Derby et al., “A single dose of a MIV-150/Zinc acetate gel provides 24？h of protection against vaginal simian human immunodeficiency virus reverse transcriptase infection, with more limited protection rectally 8-24？h after gel use,” AIDS Research and Human Retroviruses, vol. 28, no. 11, pp. 1476–1484, 2012.
[66]
International Partnership for Microbicides, “A microbicide ring to protect against HIV,” http://www.dfid.gov.uk/r4d/PDF/Outputs/Microbicides/RING_BACKGROUNDER_%20ENGLISH.pdf.
[67]
Population Council, “Critical issues for integrating SRH and HIV/AIDS services to provide dual protection against unintended pregnancy and HIV/STI acquisition,” http://www.popcouncil.org/pdfs/events/2012ICCR_Brache.pdf, http://www.popcouncil.org/pdfs/2012RH_STEPUPSymposiumReport.pdf.
[68]
J. Romano, “High-impact products: necessary attributes, development prospects, and challenges,” in Presentation at Symposium 6: Prevention of Multiple Reproductive Health Indications, Microbicides 2012 Conference, Sydney, Australia, April 2012, http://cami-health.org/convenings/Microbicides-2012.php.
