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Microbicides

A microbicide for HIV does not yet exist outside of clinical trials, but the idea is currently being researched and developed.

back to top What is a microbicide?

A microbicide is something designed to destroy microbes (bacteria and viruses) or to reduce their ability to establish an infection. A microbicide for preventing HIV infection would be applied to the vagina or rectum to prevent the virus being passed on during sex.

back to top What are the advantages of HIV microbicides?

A microbicide would share many of the advantages of an HIV and AIDS vaccine. It would be especially useful for women unable to insist on their partner using condoms, who might be able to use a microbicide without their partners knowing. However, a microbicide would not be able to prevent all forms of HIV transmission, and would require regular reapplication. Unlike vaccines, an effective microbicide must be made into a commodity that people will want to use regularly, such as a cream, gel or vaginal ring.

back to top How might an HIV microbicide work?

A microbicide could work in at least four different ways:

  • Kill or inactivate HIV
  • Stop the virus entering human cells
  • Enhance the body’s normal defence mechanisms against HIV
  • Inhibit HIV replication

The first microbicide candidates developed were made from barrier gels, among them nonxoynol-9 and cellulose sulfate. More recent trials have been testing antiretroviral-based microbicides, which aim to prevent HIV infection in the same way as PrEP might.

back to top What are the challenges in developing HIV microbicides?

There are many chemicals that kill HIV, including undiluted household bleach. But what is needed for a microbicide is something that works against HIV without causing discomfort or irritation. For example, when researchers investigated using the spermicide nonoxynol-9 as an HIV microbicide they were surprised to find it actually increased the rate of transmission, probably because it caused vaginal lesions and inflammation, which made it easier for HIV to establish an infection, even though nonoxynol-9 killed the virus in lab tests.1

For a microbicide to become popular, researchers must develop not only the active ingredient but also a microbicide that is socially acceptable, affordable and easy to apply. Ideally it would provide protection for several days or even weeks at a time.

Other major issues include how a microbicide might affect sperm and whether it might cause adverse effects for a woman's reproductive health.2

back to top How are the possible microbicides tested?

There are three phases of clinical trials that a potential mircobicide must pass through before it is judged effective and safe. Phase I tends to last between twelve and eighteen months, whereas the final phase can take up to three or four years.

  • Phase I involves a small number of volunteers to test the safety of various doses
  • Phase II involves hundreds of volunteers to further assess safety and, in some cases, positive responses
  • Phase III involves thousands of volunteers to test safety and effectiveness

The Phase IIb trial, a recent innovation, is a larger variant of the Phase II trial.

All microbicide trials provide condoms and prevention counselling to all participants, as an ethical obligation. As a result, the overall rate of HIV transmission is lowered, which means more volunteers are needed to produce a significant result. Most volunteers must be HIV-negative at the beginning of the trial, though it is also important to test safety in those who are already infected.

back to top Key microbicide trials

A computer-generated image of HIV exiting a cell A computer-generated image of HIV exiting a cell

Several microbicide candidates are currently being studied in over 20 clinical trials.3 The results of a Phase IIb trial, CAPRISA 004, were presented at the 2010 International AIDS Conference in Vienna. The randomized, controlled trial assessed the safety and effectiveness of tenofovir gel in 900 HIV-negative, sexually active women between the ages of 18 and 40 years in South Africa. The results were statistically significant, with the gel reducing the risk of HIV acquisition by 39 percent overall.4 The protective effect increased to 54 percent among women with high gel adherence. The study is the first to provide proof of concept for microbicides. Although plans for further trials are in place, funding shortfalls are currently restricting progress.5

The phase IIb, VOICE (Vaginal and Oral Interventions to Control the Epidemic) trial, investigated the use of both oral pre-exposure prophylaxis (PrEP) and a vaginal microbicide gel to prevent the transmission of HIV.6 Among the trial group, which consisted of women in South Africa, Zimbabwe and Uganda, around 1,000 women received a vaginal tenofovir gel and another 1000 received a placebo gel; each to be applied daily regardless of sexual activity. In 2011 the microbicide part of the trial was halted, as it was found that HIV incidence among women using the vaginal tenofovir gel was almost identical to incidence among women using the placebo gel.7 The lack of success was attributed to poor adherence among the women; only 22 percent of trial participants had measurable drug levels in their vaginal fluids, suggesting that they had not used the gel regularly enough.8 The study suggests that for microbicides to work, they need to require minimal daily adherence.

Following the success of the CAPRISA 004 trial, which also tested the effectiveness of a vaginal tenofovir gel, the VOICE results were largely received as a step back in the progress towards developing an effective microbicide.9 Nevertheless, a trial in South Africa, FACTS 001, studying the use of a vaginal tenofovir microbicide gel, using the same regimen as CAPRISA 004, started enrolling a planned 2,200 women across nine sites in 2011.

back to top Who is supporting research and development?

In 2009 around $236 million was invested in microbicide research and development - a 3% decrease on the previous year. About 94% of this money came from the public sector, 5% came from the philanthropic sector and <1% was accounted for by commercial companies (only $1 million).10 11

At present no major pharmaceutical firm is investing significant amounts of its own money in microbicide research because it is complex and the market is uncertain.12 As Professor Jonathon Weber has stated:

"[Microbicides] are perceived as drugs for Africa, and no one makes money from Africa"13

back to top Conclusion

If one of the microbicide candidates were successful in preventing HIV infection, it would be a while before it would become widely available. Any successful product would have to undergo review and licensing by regulatory agencies before becoming available to the public. It would take time to work out the best formulation and dosage; find a suitable delivery method; and distribute the product. Also, if an effective product is produced it may be difficult finding investors, as the microbicide will have to be available to women in low- and middle- income countries and therefore profit margins will be low.14 In addition, any successful microbicide will only be partially protective and so would have to be complemented with other prevention methods.15

Whilst it is important to ensure continued funding and support for microbicide development, it would not be helpful to be overly optimistic about the effectiveness and potential availability of such a product. A microbicide will not be a ‘silver bullet’ for ending the epidemic, but rather another tool to add to existing prevention efforts.

Nominet Winner 2012

References back to top

  1. Global Campaign for Microbicides 'Nonoxynol-9'.
  2. World Health Organization (2009, September) 'Regulatory issues in microbicide development'
  3. Alliance for Microbicide Development (2010) 'Microbicide and PrEP candidates in ongoing clinical trials, summary as of September 2009'
  4. Karim, Q.A. et al (2010) 'Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women', 19th July 2010, Sciencexpress
  5. The New York Times (2010, 3rd September) 'H.I.V. prevention gel hits snag: Money'
  6. Microbicides Trial Network (2010) 'MTN-003'
  7. Microbicide Trials Network (2011, 25th November) 'MTN Statement on Decision to Discontinue Use of Tenofovir Gel in VOICE, a Major HIV Prevention Study in Women'
  8. nam / aidsmap (2013, 4th March) 'VOICE trial's disappointing result poses big questions for PrEP'
  9. NAM/aidsmap (2011) 'Microbicide gel fails to work in large international trial'
  10. HIV Vaccines and Microbicides Resource Tracking Working Group (2011, 19th July) 'Advancing the Science in a Time of Fiscal Constraint: Funding for HIV Prevention Technologies in 2009'
  11. HIV Vaccines and Microbicides Resource Tracking Working Group (2009, July) 'Adapting to Realities: Trends in HIV prevention research funding, 2000 to 2008'.
  12. Global Campaign for Microbicides 'Financing'.
  13. The Guardian (2004, 22nd March) 'Taking prevention of Aids beyond ABC'
  14. UNAIDS (2008) 'Microbicides: challenges to development and distribution (part 2)'.
  15. UNAIDS (2008, 20th February) 'Microbicides: why are they significant? (Part 1)'