Microbicide Overview

What are microbicides? countries, and women have a heightened risk of infection due to a combination of biology and gender inequities. For Microbicides are products being developed to protect example, it is not always possible for women to negotiate healthy people from becoming infected with HIV during condom use with their partners. sex. Most microbicides contain antiretroviral (ARV) drugs that attack the virus at one of a number of points in the HIV Microbicides would help meet the needs of different women life cycle. Multiple clinical trials have shown that ARVs — at different times in their lives — and allow them to protect the same types of drugs successfully used to treat HIV/AIDS their own health. — can prevent infection when they are used consistently. What is the status of microbicide research? Some microbicides are being designed for women as vaginal Early microbicides: products in various forms such as long-acting rings, and Studies of the earliest microbicides, on-demand vaginal films and tablets. Rectal microbicides which were not based on ARVs, showed no protection are also being developed for both men and women. against HIV. Tenofovir gel: In 2010, a vaginal gel containing the ARV tenofovir was shown in the CAPRISA 004 study to reduce women’s risk of HIV infection by 39 percent when used before and after sex, providing proof-of-concept for micro- bicides. Two subsequent studies (FACTS 001 and VOICE) were unable to confirm those findings, however, due to low product use, which underscores the challenge of developing products women can use consistently. Dapivirine ring: In 2016, the monthly dapivirine ring, developed by IPM, was the first microbicide to confirm effi- cacy in two late-stage clinical trials. The ring, which slowly releases the ARV dapivirine over the course of a month, is also the first long-acting HIV prevention method. How effective is the dapivirine ring? The International Partnership for Microbicides (IPM) is In Feb. 2016, two Phase III “sister” studies, The Ring Study, focused on developing microbicides to protect women led by IPM, and ASPIRE, led by our clinical trial partner the from HIV during sex with a male partner. There will be no Microbicide Trials Network, showed that the monthly ring single solution to ending the epidemic — stopping HIV will safely prevented HIV in about one in three women ages 18- require a variety of options. Safe and effective microbicides 45 overall. ASPIRE also showed that the ring cut HIV risk could have a profound impact on the epidemic as part of a by more than half among women older than 21, who also comprehensive prevention strategy that includes condoms, used the product more consistently. This finding suggests oral ARV pills (known as pre-exposure prophylaxis or that greater protection can be achieved with more consistent PrEP) and, one day, a vaccine. ring use, or adherence. Why microbicides? What are the next steps for the ring? Next steps include two planned open-label studies, called HIV/AIDS is the leading cause of death globally in women DREAM and HOPE, designed to provide the ring to women ages 15-44, and young women in sub-Saharan Africa are up who participated in The Ring Study and ASPIRE, respec- to five times as likely to have HIV as young men. tively, and to understand if ring use will increase now Although a range of prevention strategies exists, they have that the product’s safety and efficacy are known. Another not done enough to stop the virus’s spread. Heterosexual sex planned study will focus on young women and adolescents is the primary mode by which HIV spreads in developing in Africa, assessing the safety of and adherence to the ring

IPM Headquarters 8401 Colesville Road • Suite 200 • Silver Spring, MD 20910 USA TEL: +1-301-608-2221 FAX: +1-301-608-2241 www.IPMglobal.org IPM South Africa 63 Main Road • Paarl 7646, South Africa • P.O. Box 3460 TEL: +27-21-860-2300 FAX: +27-21-860-3208/1000 @IPMicrobicides and PrEP. Findings from these studies will provide insights based on a clear understanding of the trial, including the into product adherence challenges and help identify ap- risks and benefits of trial participation. The informed con- proaches to address them. sent process must be consistent with International Confer- ence on Harmonisation Good Clinical Practice and local Given the ring’s promise for many women at high risk, IPM country guidelines. Informed consent is an ongoing process is also pursuing regulatory approval for its use in developing that requires periodic and ongoing discussions with partici- countries. The ring could be approved in some locations in pants to ensure their continued understanding of the trial. Africa in late 2018. In addition, as part of the standard of care guidelines for Why do we need multiple options? clinical trials, participants receive ongoing HIV and STI Existing HIV prevention options work for some, but not all, risk-reduction counseling, condoms, pre- and post-HIV test women. Women need a range of new self-initiated preven- counseling, family planning counseling and treatment for tion tools they can choose from that fit within the context of curable STIs that are identified. Participants are also re- their lives. Having multiple prevention options is not simply ferred for support, care and treatment in the event that they a best-case scenario — it is the only scenario that can end become infected with HIV or require medical attention for the epidemic. any other condition. To that end, several microbicides containing multiple ARVs How are local communities involved? are in earlier stage development as are multipurpose preven- tion products designed to prevent both unintended preg- nancy and HIV infection — and sometimes other sexually transmitted infections (STIs), too. Other approaches in early phase study include long-acting injectable ARVs, rectal gels, broadly neutralizing antibodies and vaccines. How are safety and efficacy studied? All microbicide candidate products go through rigorous laboratory screening and testing to ensure an adequate safe- ty profile before being studied in humans. Clinical trials are carried out sequentially, first to determine the safety of the product (no significant side effects) and then to test its efficacy. Initial safety trials involve small numbers of women who participate under carefully con- An outreach worker describes the monthly dapivirine ring. trolled clinical conditions. Larger safety trials involving a wider range of women over longer periods are then con- In countries where clinical trials are conducted, IPM and its ducted to collect broader safety data. local research partners have implemented broad-based pro- grams to engage community members. Information about Efficacy trials are then performed to test the ability of the microbicides and clinical trials is provided in local languag- microbicide to prevent HIV infection. These trials involve es to trial participants and key stakeholders, including local large numbers (hundreds to thousands) of women, and officials, women’s groups, medical professionals, the media, need to be conducted in locations where new HIV infec- traditional leaders, ministries of health and others. Ongoing tions occur at a high rate. This allows researchers to assess training and support for those involved in the clinical trial the difference in infection rates between those women who process — clinical investigators, research scientists, nurses, use the active microbicide and those who use a placebo, counselors, community health workers and project manage- which contains no active drug. IPM will make microbicides ment staff — is also provided. available in trial countries, if found effective and approved. Conclusion What ethical standards guide clinical trials? Offering safe and effective microbicides for women in All clinical trials, including microbicide trials, must be con- developing countries promises to be one of the great public ducted according to international and national regulatory health accomplishments of our generation. Realizing that and ethics guidelines to protect participants’ well-being, and potential requires continued financial resources and politi- guarantee the ethical and scientific integrity of the results. cal will to deliver promising innovations to the women who Informed consent is the cornerstone of ethical trial conduct. urgently need them. Clinical research teams must ensure that all participants in microbicide trials have freely given their informed consent www.IPMglobal.org June 2016