(February 2006) The HIV/AIDS pandemic continues to become increasingly feminized. In 2005, 17.5 million women worldwide were living with HIV—one-half of all people infected, and 1 million more women than in 2003. Sub-Saharan Africa, where the epidemic has been most severe, is now home to 77 percent of all women with HIV.1

Women are particularly vulnerable to HIV infection. Biologically, women are more than twice as susceptible to HIV as men because of differences in reproductive anatomy.2 Poverty and gender inequality exacerbate this biological vulnerability, rendering many girls and women unable to negotiate with older or more powerful male partners over condom use, abstinence, or faithfulness. In one study in Zimbabwe and South Africa, 40 percent of women who had only one lifetime partner and who had abstained from sex until age 17 still became infected with HIV.3

Women therefore desperately need HIV prevention tools they can initiate and control. Microbicides (products applied vaginally to reduce HIV transmission during sexual intercourse) are a strong candidate to fill this need.4 One study indicates that a microbicide that is effective only 60 percent of the time could still prevent 2.5 million new HIV infections in low-income countries over a three-year span—even if used by only 20 percent of women in these countries.5

But a number of challenges—most important, obtaining funding and commitment from policymakers and pharmaceutical companies—have hampered the development of microbicides. Lessons learned from the female condom, a female-initiated tool in which male involvement and cost are important for usage rates, could provide guidance to microbicide development and utilization by its target audience. (See “Obstacles Remain to Wide Adoption of Female Condom“). These lessons need to be applied quickly: Experts from microbicide advocacy groups warn that attaining the Millennium Development Goals could be in jeopardy without widespread use of such tools.6

Challenges To Microbicide Development

Developing microbicides takes a long time—perhaps a decade or longer. Part of the long development period is attributable to the lengthy and expensive safety, effectiveness, and efficacy testing that any drug undergoes before receiving approval from the U.S. Food and Drug Administration (see figure). A significant portion of the time involves recruiting the large number of human subjects needed to confirm that a product will do what it purports to do (efficacy).


The Pipeline for Microbicide Development, 2005

10-20 products
6 products
3 products
5 products
Laboratory Testing
2-6 Years
Phase 1
(Safety)
Phase 2
(Safety)
Phase 3
(Efficacy)
25-40 people
200-400 people
3,000-10,000 people

Source: Global Campaign for Microbicides (www.global-campaign.org).


To speed the process for microbicides, study designs have been developed that combine Phase 2 and 3 characteristics—an ability to measure both the safety of a microbicide along with its effectiveness against HIV.

Microbicide trials are taking place around the world, with researchers and developers currently working on more than two-dozen potential (“candidate”) products.7 Five candidate microbicides entered large-scale efficacy trials in 2005, and a new second-generation of microbicides enter safety trials this year, where they will receive rigorous evaluation and clinical testing so that the best can be fast-tracked to clinical trials. While the first-generation microbicides are predicted to be about 50 percent to 60 percent effective, promising second- and third-generation research leads mean that subsequent products could be more effective.8

However, financing of both research and development and clinical trials is still a concern. Experts estimate that sufficient financial resources and collaborative efforts among private and public partners should bring effective microbicides to market within the next five to 10 years.9 But despite estimates of a potential $1.8 billion market for a successful microbicide against HIV by 2020, private pharmaceutical companies have been reluctant to conduct the research and development necessary to bring a product to market because financial profits will be small.10

Sadly, this reluctance means a number of microbicide candidates remain in a pre-research phase. According to the International Partnership for Microbicides (IPM), sustaining the momentum for microbicide product development and improvement will require a steady flow of new candidates through the pipeline.11

Once microbicide candidates are fast-tracked for development, another challenge is developing the capacity for large clinical trials on the ground.12 Pam Norick, chief of external relations for IPM, suggests that one of the primary challenges is to garner enough funds to conduct robust clinical trials in the field, where a single Phase 3 trial can cost over $100 million. According to Norick, the trials have to be conducted effectively so that there is benefit to and participation from the community and so that the product shows significant efficacy in addition to safety.

Overall lack of funding for getting a microbicide to the market is the most significant challenge. Although funding for research and development from the public and philanthropic sectors has more than doubled in the past five years (from $65 million to $142 million in 2004), investment falls far short of the estimated $280 million per year that advocacy groups say is required.13

Clear Advances In An Intricate Process

Advocacy groups such as the Global Campaign for Microbicides, Global Coalition on Women and AIDS, Alliance for Microbicide Development, and IPM accomplished an important goal on World AIDS Day 2005: Four European governments—the United Kingdom, Republic of Ireland, Denmark, and Sweden—pledged nearly $30 million dollars to the development and increased accessibility of microbicides and other critically needed HIV prevention technologies for women.14

“Today’s funding looks to the long-term and will encourage the development of…microbicides that will benefit both the developing and developed world,” Prime Minister Tony Blair of the United Kingdom and current president of the G8 and European Union told IPM at the World AIDS Day announcement.15

While this $30 million is only 10 percent of the annual investment needed in these areas, it was an important commitment from the public sector and followed on the heels of an essential contribution from the private sector in late fall 2005. Two pharmaceutical companies, Merck & Co. and Bristol-Myers Squibb, granted royalty-free licensing agreements to IPM to develop, manufacture, and distribute new antiretroviral compounds as potential microbicides. These compounds are part of a new class of antiretrovirals called “entry inhibitors,” designed to prevent the virus from entering host cells in the body.

Opening up such bottlenecks has moved the world closer to an available, effective, and efficacious microbicide, although more investment and commitment are needed. According to Norick: “The field is coming of age. Donors have increased confidence in the science and clinical activities in the field, and are committed to the idea that women urgently need new tools to prevent HIV.”


Heidi Worley is a senior policy analyst at the Population Reference Bureau.


References

  1. UNAIDS/World Health Organization (WHO), Global Summary of the AIDS Epidemic: December 2005 (Geneva: WHO, 2005).
  2. Global Coalition on Women and AIDS, “Microbicides, Women and AIDS,” accessed online at http://womenandaids.unaids.org/resources/default.html, on Nov. 29, 2005.
  3. A. Meehan, “Prevalence and Risk Factors for HIV in Zimbabwean and South African Women,” paper delivered at the XV International AIDS Conference, July 11-16, 2004.
  4. Microbicides can take the form of gels, creams, films, suppositories, sponges, or vaginal rings that release their active ingredient gradually.
  5. Public Health Working Group of the Microbicide Initiative, The Public Health Benefits of Microbicides in Lower-income Countries: Model Projections (New York: Rockefeller Foundation, 2002): 7.
  6. International Partnership for Microbicides (IPM), “Microbicides: An Essential HIV Prevention Strategy for Achieving the Millennium Development Goals” (September 2005), accessed online at www.ipm-microbicides.org, on Dec. 1, 2005.
  7. Alliance for Microbicide Development, “Microbicide Researchers and Developers,” accessed online at http://secure.microbicide.org/NetReports/ResDev.aspx, on Dec. 2, 2005.
  8. Eldis, “Microbicides: Quick Guide Through the Key Issues,” accessed online at www.eldis.org, on Dec. 4, 2005.
  9. IPM, “Organizational Overview,” accessed online at www.ipm-microbicides.org, on Nov. 29. 2005.
  10. IPM, “Organizational Overview.”
  11. IPM is a private-public partnership established in 2002 to accelerate the development and accessibility of vaginal microbicides. With support from the Gates and Rockefeller Foundations, the United Nations, the World Bank, and several European governments, IPM screens compounds, designs optimal formulations, establishes manufacturing capacity, develops trial sites, and conducts large-scale efficacy trials in developing countries.
  12. IPM, the Global Campaign for Microbicides, and the Alliance for Microbicide Development, “Request to the G8 for Increased Investment in Microbicide Research and Development to Slow HIV Infection Rates among Women in Developing Countries,” accessed at www.ipm-microbicides.org, on Nov. 29, 2005.
  13. HIV Vaccines and Microbicides Resource Tracking Working Group, “Tracking Funding for Microbicide Research and Development: Estimates of Annual Investments 2000 to 2005,” accessed online at www.microbicide.org, on Jan. 23, 2006.
  14. The Global Campaign for Microbicides is an international effort to build support among policymakers, opinion leaders, and the general public for increased investment into microbicides and the timely development, introduction, and use of new prevention technologies. Launched in 2004 by the Joint United Nations Programme on HIV and AIDS (UNAIDS), the Global Coalition on Women and AIDS is a worldwide alliance of civil society groups, networks of women with HIV and AIDS, governments, and UN organizations that works at global, regional, and national levels to highlight the impact of AIDS on women and girls as well as to mobilize actions to enable women and girls to protect themselves from HIV and receive the care and support they need. Founded in 1998, the Alliance for Microbicide Development is a global nonprofit organization representing a coalition from over 200 biopharmaceutical companies, nonprofit research institutions, and health advocacy groups. The alliance helps speed the development of safe, effective, and affordable microbicides through advocacy, education, monitoring, research, troubleshooting, convening dialogue around key issues, participating in dynamic and committed partnerships, and networking across constituencies, disciplines, and sectors.
  15. IPM, “Statement: Nearly US$30 million Committed to Microbicide Development,” accessed online www.ipm-microbicides.org, on Dec. 2, 2005.