Be The Generation To End The AIDS Epidemic
Photo by International Partnership for Microbicides
Worldwide, nearly 37 million people are living with HIV. Although many important strides have been made in the treatment of HIV, the prevention of HIV continues to be great a challenge. Approximately 2 million people contract HIV annually – about 5,600 every day.
HIV is most often is spread through condomless sex, and efforts to promote abstinence, monogamy, and the use of condoms have not been enough to stop the epidemic--nor are these approaches practical for many people. Microbicides are products applied inside the vagina or rectum to protect against HIV transmitted through sex. Most microbicides being tested include antiretroviral (ARV) drugs.
Types of microbicides furthest along in development and testing include vaginal rings, which release an active anti-HIV drug over a few weeks or months, and rectal microbicide gels. Other formulations being developed include vaginal creams and films as well as rectal douches and suppositories. Although a microbicide has not yet been approved and made available for widespread use, finding one that is safe and effective would be very important to the global response against HIV/AIDS, especially for populations who are particularly vulnerable. These include cisgender women in sub-Saharan Africa, adolescents, pregnant and breastfeeding women, men who have sex with men, and transgender women.
Microbicides are products applied inside the vagina or rectum to protect against HIV transmitted through sex.
Vaginal microbicides are being primarily designed as films and rings, which release an anti-HIV drug gradually over time. Two studies (Phase III clinical trials) have reported results on the effectiveness of a monthly-use vaginal ring containing the anti-HIV drug, dapivirine. Numerous other ring studies are completed, underway, or being planned in different populations of women, including those who are pregnant or breastfeeding, and in young women and adolescent girls.
“Dual-purpose microbicides” refer to products that can simultaneously prevent HIV and unintended pregnancy.
Work also is underway to develop rectal microbicides for use by both men and women who practice anal sex. Like a vaginal microbicide, a rectal microbicide would be an HIV prevention strategy that doesn’t have to be controlled by a sexual partner.
In one study, (the first Phase II trial of a rectal microbicide), researchers tested the safety, drug absorption, and acceptability of a reduced glycerin formulation of tenofovir gel, applied rectally, among men who have sex with men and transgender women. Researchers are also exploring new potential products and delivery methods such as douches and fast-dissolving tablets for use in the rectum. These products, currently being tested, are intended to be easier to use and have the potential to enhance the sexual experience.
Most microbicides prevent the transmission of HIV by blocking the attachment of HIV to cells or by preventing the infection from spreading.
Microbicides can help protect against HIV and possibly other sexually transmitted infections, but they are not a cure for HIV.
HIV affects many populations in many places around the world, and people need a variety of options to protect themselves.
Condoms are an effective HIV prevention method, but many people can’t or don’t use them every time they have sex. Similarly, pre-exposure prophylaxis (PrEP) has been shown to be highly effective, but not everyone can or will want to take a pill every day for HIV prevention. Just as there are multiple choices in contraception to prevent pregnancy, microbicides could give people an additional option for HIV prevention.
Importantly, microbicides represent an HIV prevention strategy that doesn’t have to be controlled by a sexual partner.
All drugs go through a lengthy development and testing process over many years before a product is determined safe and effective for people to use.
Various types of microbicides are being tested, but none has yet been approved by the U.S. Food and Drug Administration for use outside of clinical studies.
Researchers are currently collecting comprehensive data on the dapivirine vaginal ring with plans to submit these data to regulators. Once submitted, the first regulatory approvals for the ring could be granted in 2018 or 2019.
Determining the safety and effectiveness of a rectal microbicide must be established separately from a vaginal-use product before an HIV prevention product for anal sex can be approved for widespread use.
Vaginal rings are flexible products that fit high inside the vagina and allow for the slow, continuous delivery of a drug or multiple drugs over a period of weeks or months. Vaginal rings can be inserted and removed by the user. In the U.S. and Europe, vaginal ring products are licensed for both pregnancy prevention and hormone replacement therapy.
The drug dapivirine is the furthest along in testing for use in a vaginal microbicide ring, with results from two effectiveness studies reported in early 2016: the ASPIRE trial led by MTN and The Ring Study led by the International Partnership for Microbicides, which developed the ring. More than 4,500 women from Africa took part in the two trials, with results indicating the ring was safe and reduced rates of HIV by about one-third. Among women who used the ring the most, HIV risk was cut by more than half across all analyses, and in some, by 75 percent or more.
Open label follow-up studies currently underway will help researchers learn more about the dapivirine ring’s safety and acceptability. MTN is also conducting a number of studies of the ring in different populations, including in adolescent girls and young women, who are particularly vulnerable to HIV in sub-Saharan Africa.
Although most microbicide research has focused on products to prevent HIV transmission through vaginal sex, anal sex is also practiced by many people around the world. According to some estimates, the risk of becoming infected with HIV through anal sex is 20 times greater than vaginal sex because the rectal lining (the mucosa) is thinner and much more fragile than the lining of the vagina.
In the first Phase II trial of a rectal microbicide, completed in 2016, researchers found that a reduced glycerin formulation of tenofovir gel was safe and effective, particularly when used around the time of sex compared to daily use, among men who have sex with men and transgender women. Researchers continue to explore new potential products and delivery methods for rectal microbicides, including the DREAM (Delivery of Rectal Enema as Microbicide) program, which is exploring the delivery of a rectal microbicide as a single dose enema, and PREVENT (Griffithsin-based Rectal Microbicides for Prevention of Viral Entry), which is addressing the need for a non-ARV based rectal microbicide. Through exploring new products and delivery methods, researchers hope to develop products people would want to use that incorporate desirability into the design, function, and future marketing.
Many types of participant adherence measures are built into MTN studies, including face-to-face interviews and the use of Audio-Computer Assisted Self Interviewing, which allows participants to answer questions about condom use, sexual behavior, and product use. Tests that detect the presence of drug in blood are also used to help determine whether participants are using their assigned study products. In some studies, blood test results are shared with participants as part of their ongoing adherence counseling sessions.
Testing many products is necessary before finding a microbicide that will be safe and effective against HIV and also easy and acceptable to use. Different products work in different ways. One approach may suit some people but not others. Individual needs and preferences can also change, which is why a variety of products are needed. A handful of candidate microbicides are in various stages of clinical study, and additional compounds are in early stages of development.
All MTN studies are designed according to strict ethical and scientific guidelines with numerous measures to protect the safety and wellbeing of participants. As with all NIH-funded studies, MTN studies incorporate a multi-tiered safety review process and are conducted with oversight from regulatory and research authorities. Before study activation, MTN protocols undergo extensive and rigorous review by NIAID, the U.S. Food and Drug Administration, institutional review boards, and receive approval by in-country regulatory and ethics bodies for each of the clinical trial sites before they begin. IRBs ensure that studies are scientifically valid and ethically conducted and provide oversight throughout the duration of a trial.
Written informed consent is obtained from each participant prior to screening and enrollment in any study conducted by the MTN. The process ensures that individuals understand the study procedures as well as possible risks and benefits of the study. Participants are under no obligation to participate and can leave a study at any time, without consequence.
The MTN subscribes to the Good Participatory Practice Guidelines (GPP) for HIV prevention research, developed by the Joint United Nations Programme on HIV/AIDS and AVAC. GPP addresses the importance of effective communication and meaningful community engagement for the successful and ethical conduct of HIV prevention trials. For larger MTN studies, face-to-face consultations are conducted in countries with clinical sites participating in the studies. The meetings, planned in close partnership with the sites and local community member and advocacy organizations, address questions and concerns about the protocol and solicit feedback that often leads to changes in the protocol’s design and implementation plan.
All MTN trial sites also have active Community Advisory Boards and community engagement programs for building and sustaining partnerships with local non-governmental organizations, civil society, news media, local physicians, health department officials, and other stakeholders.
The Microbicide Trials Network (MTN) is an HIV/AIDS clinical trials network founded in 2006 by the National Institute of Allergy and Infectious Diseases (NIAID), with co-funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Mental Health, all part of the U.S. National Institutes of Health (NIH). The MTN brings together international investigators, community stakeholders, and industry partners who focus on developing and evaluating microbicides. The MTN is also committed to the development of dual-purpose products that could offer both HIV protection and pregnancy prevention.
MTN trials are designed and conducted to support the approval and licensing of products. Because the effectiveness of a product often depends on how consistently it is used, behavioral science is a key feature within MTN studies to gain understanding of the needs and desires of different groups who are particularly vulnerable to contracting HIV. More than 25 clinical research sites on four continents have partnered with the MTN in conducting clinical trials of microbicides.