Microbicides

Microbicides are products applied inside the vagina or rectum to protect against HIV transmission 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 could simultaneously prevent HIV and unintended pregnancy.

Work also is underway to develop rectal microbicides for use by all people 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 would prevent the transmission of HIV by blocking the attachment of HIV to cells or by preventing HIV from spreading.

Microbicides could 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 regularly take pills or shots 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.

The dapivirine vaginal ring is the first microbicide to be approved for HIV prevention. In 2021, it was approved in some countries in Africa for cisgender women. It was withdrawn from review by the Food and Drug Administration (FDA) in the United States, meaning it will not be available for people in the US. Other HIV prevention options in the US remain, such as oral and injectable PrEP. The dapivirine vaginal ring will continue to be approved in countries around the world where cisgender women need it most.

To date, no rectal microbicide products have been approved for widespread use. Testing in research continues so that someday people may use rectal microbicides for HIV prevention during anal sex.

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. FDA for use outside of clinical studies.

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.

Two major studies reported on the safety and efficacy of the drug, dapivirine, 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 have also helped researchers learn more about the dapivirine ring’s safety and acceptability. The combined results of all of the research on the dapivirine vaginal ring led the World Health Organization to approve the ring as an option for HIV prevention for cisgender women in January 2021, which allows for further country-level approvals.

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 likelihood of acquiring 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. These include the possibility of delivering a rectal microbicide as a single dose enema as well as exploring non-ARV based rectal microbicides. 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 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 the 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.

All studies funded by the National Institute of Allergy and Infectious Diseases are designed according to strict ethical and scientific guidelines with numerous measures to protect the safety and wellbeing of participants. All NIH-funded studies incorporate a multi-tiered safety review process and are conducted with oversight from regulatory and research authorities. Before study activation, protocols undergo extensive and rigorous review by the National Institutes of Allergy and Infectious Diseass, the U.S. Food and Drug Administration, and institutional review boards. Studies must also receive approval by in-country regulatory and ethics bodies for each clinical trial sites before a study can 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 funded by NIAID. 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.

NIAID-funded research 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 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.

Trial sites may 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.