HIV in Canada: A primer for service providers

 

Prevention Approaches in Development: Microbicides and Vaccines

Key Points

  • Scientists are working to develop new approaches to help prevent HIV, including microbicides and vaccines; however, these approaches have not yet been proven sufficiently effective.
  • Microbicides are experimental products that are applied to the vagina or rectum and have the potential to help prevent HIV from being transmitted during sex.
  • Vaccines are experimental products taken by people who are HIV negative and have the potential to help prevent acquisition of HIV.

There are a number of approaches to preventing HIV that are highly effective, and others that have been proven partially effective. Besides these established approaches, scientists are working to develop new tools that can also help to prevent HIV, to increase the range of available options. There has been significant research to develop preventative microbicides and vaccines, though no microbicide or vaccine has been proven sufficiently effective to date.

Microbicides

Microbicides are experimental products that have the potential to help prevent the sexual transmission of HIV and/or other sexually transmitted infections (STIs). Microbicides may take a variety of forms – gels, creams, suppositories, films, sponges or rings – and are applied to or inserted in the vagina or rectum. Microbicides can either act as a physical barrier to prevent HIV from getting into the body or can prevent the replication of the virus once it has entered the body.

Six of the first microbicides to be tested in clinical trials were used vaginally by women and did not show any success in preventing HIV infection. In fact, some may have even increased the risk of acquiring HIV because of damage caused to the vaginal mucous membrane.

Researchers are now investigating microbicides that contain antiretroviral drugs, which can be considered a type of pre-exposure prophylaxis (PrEP). These microbicides would act after HIV has made its way into the body, by helping to prevent the virus from multiplying and spreading throughout the body.

A vaginal microbicide gel containing the antiretroviral drug tenofovir has been evaluated for effectiveness. Results found that the gel was more effective when used consistently; however, the risk reduction was only 54% among consistent users in one study. Additional studies looking at this gel are ongoing.

Two studies evaluated the effectiveness of a monthly vaginal ring containing the antiretroviral drug dapivirine, showing modest protection. The ASPIRE trial found a monthly vaginal ring reduced the overall risk of HIV transmission by 27% among women enrolled in the study, regardless of how consistently they used the ring. Similarly, The Ring Study found a 31% reduction in HIV transmission. In both studies, the ring was most effective for women who used it consistently, and the ASPIRE trial found that HIV risk was reduced by 56% among women over the age of 21, who also were more likely to use the ring consistently. In these studies, women were not told whether they were given the dapivirine ring or a placebo ring containing no drug.  Both of these studies continued as open-label extensions (called HOPE and DREAM, respectively), where all participants were offered the dapivirine ring and told that it contains the study drug.  In HOPE th risk of HIV transmission was reduced by 39% and in DREAM the risk was reduced by 63%. Both studies found a modest increase in consistent use of the ring compared to the earlier trials.

A gel specially formulated for rectal use is also in development although it has not yet been evaluated for effectiveness against HIV infection.

No microbicide has been approved for HIV prevention in any part of the world; however, the dapivirine ring is the first microbicide to be submitted for regulatory approval, which is currently pending in Europe and Africa.

Vaccines

The term vaccine is most commonly used to describe products that are designed to prevent individuals from getting a disease (known as preventative vaccines). Vaccines also have public health benefits: if enough people are vaccinated this creates “herd immunity,” where the vaccinated part of the community can provide protection to the rest of the community.

An HIV preventative vaccine would be taken by people who are HIV negative to reduce their risk of acquiring HIV. The development of an effective preventative HIV vaccine has proven to be difficult because of the complexity of the virus and the body’s response to the virus. First, HIV attacks the immune system immediately, so that there is very little time for the immune system to develop a response to prevent infection. Second, a main route for HIV to enter the body is the wet tissues of the mucous membranes lining the rectum, penis or vagina. Researchers are only just beginning to understand how the immune system works in mucosal tissues, so it will take many years before they can fully map the complex changes that HIV triggers in those tissues. Third, the virus mutates, constantly changing its outer layer, making it especially difficult for the immune system to keep up with these changes. An additional challenge is that HIV gets into cells of the immune system and elsewhere deep inside the body, essentially allowing it to hide from the immune system.

All vaccine candidates have failed to provide protection against HIV, except for the combination of two vaccines known together as the Thai prime-boost vaccine. The study that tested this vaccine gave participants six injections over six months, and followed them for three years. After one year, there were 60% fewer infections among those who received the vaccine compared to those who received a placebo. However, this difference decreased to 31% by the end of three years. This level of protection was not high enough to warrant approval of this vaccine for use in any part of the world.

There are currently several large trials underway that are testing the effectiveness of vaccines.  Scientists have developed a modified version of the vaccine used in the Thai trial, and a large trial called HVTN 702 has launched in South Africa to test its effectiveness. The Antibody Mediated Prevention (AMP) trials are testing the effectiveness of an HIV antibody given intravenously among men and trans people who have sex with men (HVTN 704 / HPTN 085), and among women (HVTN 703 / HPTN 081). Another large study is underway testing the effectiveness of a combination of two experimental vaccines among women (HVTN 705). These studies are all in the early stages, and no preliminary results have yet been released.

No HIV vaccine has been approved for use in any part of the world.

Resources

Microbicides

Microbicides for HIV prevention – AVAC fact sheet

Vaccines

HIV vaccines: An introductory fact sheet – AVAC fact sheet

Sources

  1. Hillier SL, Moench T, Shattock R, et al. In vitro and in vivo: the story of nonoxynol 9. Journal of Acquired Immune Deficiency Syndromes. 2005;39(1):1.
  2. McCormack S, Ramjee G, Kamali A, et al. PRO2000 vaginal gel for prevention of HIV-1 infection (Microbicides Development Programme 301): a phase 3, randomised, double-blind, parallel-group trial. The Lancet. 2010 Oct 16;376(9749):1329–1337.
  3. Carraguard Phase II South Africa Study Team. Expanded safety and acceptability of the candidate vaginal microbicide Carraguard® in South Africa. Contraception. 2010;82:563–571.
  4. Feldblum PJ, Adeiga A, Bakare R, et al. SAVVY vaginal gel (C31G) for prevention of HIV infection: a randomized controlled trial in Nigeria. PloS One. 2008;3(1):e1474.
  5. Abdool Karim SS, Richardson BA, Ramjee G, et al. Safety and effectiveness of BufferGel and 0.5% PRO2000 gel for the prevention of HIV infection in women. AIDS. 2011 Apr 24;25(7):957–966.
  6. Obiero J, Mwethera PG, Hussey GD, et al. Vaginal microbicides for reducing the risk of sexual acquisition of HIV infection in women: systematic review and meta-analysis. BMC Infectious Diseases. 2012;12:289.
  7. Abdool Karim Q, Abdool Karim SS, Frohlich JA, et al. Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women. Science. 2010 Sep 3;329(5996):1168–1174.
  8. Friend DR, Kiser PF. Assessment of topical microbicides to prevent HIV-1 transmission: concepts, testing, lessons learned. Antiviral Research. 2013 Jul 8;99(3):391–400.
  9. Baeten JM, Palanee-Phillips T, Brown ER, et al. Use of a vaginal ring containing dapivirine for HIV-1 prevention in women. New England Journal of Medicine. 2016 Dec 1:375(22):2121–2132.
  10. Nel A, van Niekerk N, Kapiga S, et al. Safety and efficacy of a dapivirine vaginal ring for HIV prevention in women. New England Journal of Medicine. 2016 Dec 1;375(22):2133–2143.
  11. Baeten J, Palanee-Phillips T, Mgodi N, et al. High adherence and sustained impact on HIV-1 incidence: Final results of an open-label extension trial of the dapivirine vaginal ring. Oral presentation at: International AIDS Society Conference 2019, Mexico City, Mexico, 2019. Abstract TUAC0203. Available from: http://programme.ias2019.org/Abstract/Abstract/3219.
  12. Nel A, Malherbe M, Mans W, et al. Safety, adherence and HIV-1 seroconversion in DREAM – An open-label dapivirine vaginal ring trial. Oral presentation at: 9th South African AIDS Conference, Durban, SA, 2019. Available from: https://www.ipmglobal.org/content/final-results-open-label-study-ipm’s-dapivirine-vaginal-ring-show-increased-use-and-suggest
  13. Rerks-Ngarm S, Pitisuttithum P, Nitayaphan S, et al. Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. New England Journal of Medicine. 2009 Dec 3;361(23):2209–2220.
  14. Haynes BF, Liao H-X, Tomaras GD. Is developing an HIV-1 vaccine possible? Current Opinion in HIV and AIDS. 2010 Sep;5(5):362–367.
  15. Hankins CA, Glasser JW, Chen RT. Modeling the impact of RV144-like vaccines on HIV transmission. Vaccine. 2011 Aug 18;29(36):6069–6071.
  16. Abbasi J. Large HIV vaccine trial launches in South Africa. JAMA. 2017 Jan 24;317(4):350.
  17. HVTN and HPTN announce initiation of antibody mediated prevention (AMP) study. Seattle, WA and Durham, NC: HVTN and HPTN; 2016.
  18. National Institute of Allergy and Infectious Diseases, 2017. NIH and Partners Launch HIV Vaccine Efficacy Study. Bethesda, MD: NIAID.