Whether, when, and how microbicide development proceeds depends on the U.S government, and the federal Division of AIDS has suggested this development may no longer be a priority. It’s wrong.
The first proven microbicide to prevent HIV may be ready for market by the end of the decade. That’s the good news. The bad news: Although there are numerous candidate microbicides in the research pipeline, this first one could end up being the only one to become publicly available. That’s because of a push to eliminate funding for research of these vital tools. The public has until November 30 to comment on such a move. More on that later.
For over 25 years, women have been calling for an HIV prevention tool that is woman-initiated, easy to use, undetectable during sex and, ideally, comes in both contraceptive and non-contraceptive forms. Research to develop such products, called microbicides, started in 1992.
Twenty-five years later, a vaginal ring, replaced monthly, is now undergoing regulatory review by the European Medicines Agency, the first microbicide to make it to this point. The International Partnership for Microbicides plans to submit it to the South African Health Products Regulatory Authority (South Africa’s equivalent of the FDA) in early 2018, followed later by submissions to other national regulatory authorities in sub-Saharan Africa. If the ring is approved, the soonest it is currently projected to be available in some countries is late 2019. It will be the realization of a dream almost three decades in the making.
Like the contraceptive NuvaRing, this microbicidal ring is a hollow silicone device—but loaded with dapivirine, an anti-HIV drug, that is released gradually over the course of a month. In clinical trials, the ring reduced new HIV infections by 56 percent among women who used it consistently as instructed.
The chance to cut one’s HIV risk in half is big news, indeed, in areas where most of the 25- to 29-year-olds with HIV (two-thirds) are women, and where only about half of all adults between 25-49 years old report using condoms regularly. Researchers estimate that this vaginal ring, alone, could “avert at least a million HIV infections [globally] over the next 20 years.”
Oral pre-exposure prophylaxis (PrEP), a pill to prevent HIV, is a new prevention strategy that offers much higher levels (over 90 percent) of protection if taken daily. A recent demonstration project among young women in South Africa, however, showed that even while getting reminders to take a pill daily, only 57 percent of participants had detectable levels of the prevention drug in their blood at week 12, and 38 percent by week 24. This suggests that the higher efficacy of the pills can be offset by inconsistent use when daily adherence is required.
The dapivirine ring is just the first of several microbicide candidates under development. Researchers are now testing the feasibility of longer-lasting, multi-purpose rings loaded with both an anti-HIV drug and a contraceptive, thus preventing both HIV and pregnancy simultaneously for up to three months. One-time use, fast-dissolving vaginal films and tablet inserts (to be inserted before sex) are also being tested.
Several “behaviorally congruent” rectal microbicide products are also in development. These products are formulated to look and feel like the douches and lubricants that people often use before or during anal sex—but have the advantage of containing anti-HIV drugs. Thus, they should fit comfortably into common sexual behaviors while also providing protection to the user and her/his partner.
Why Would Microbicide Development Stop Now?
Whether, when, and how microbicide development proceeds depends on the U.S government simply because it has provided almost all the funding so far to develop HIV prevention tools, including PrEP, microbicides, and the (still elusive) HIV vaccine. This funding has been allocated by the Division of AIDS (DAIDS) at the National Institute of Allergy and Infectious Diseases (NIAID), which is part of the National Institutes of Health (NIH).
Between 2000-2016, for example, over $3 billion was spent globally on microbicides research and four times that amount—more than $12 billion—on vaccine development. Almost all of this money (93 percent of the vaccines funding and 84 percent of the microbicides funding in 2016, for example) came from DAIDS.
Now, however, the government is looking to reduce funding for all kinds of important public health research, including for HIV and AIDS. DAIDS Director Carl Dieffenbach announced earlier this year that he will be leading the NIH’s effort to “refine the HIV research enterprise” by prioritizing funding for HIV prevention products that are both long-acting (work in the body for six months or longer) and systemic (affecting the whole body). Vaccines, long-term injectable PrEP, and implants meet this definition. But microbicides do not.
Microbicides are instead localized, only affecting the part of the body that needs protection; reversible, because drug levels do not remain in the body long after use; short-acting, designed to be used only at the time of sex (the vaginal ring is an exception to this); and user-controlled, meaning not injected or inserted by a medical provider.
One of DAIDS’ arguments against microbicides is that “it has not been demonstrated that the most vulnerable users would choose or adhere to these products.” This is based on the results of a few microbicide gel trials and two ring trials, in which ring use among some participants was lower than expected. Additional research is pending to see if the low rates of ring use among younger women were motivated by physical, social, or behavioral factors.
Two “open-label” studies are also underway to assess ongoing interest in the product. Once the effectiveness of a new product has been proven, an open label trial is done to see how participants feel about using it. Typically, uptake and adherence is significantly greater in open-label trials because participants know they are all getting the real product and not being randomly assigned to either the real drug or the placebo (or fake drug), as occurs in the effectiveness trial.
The question of ring acceptability among younger women, in particular, is also a matter of ongoing study. Between 2014-2016, a U.S. study enrolled 96 sexually active girls (ages 15-17) in six cities and found that almost all (95 percent) participants described the ring as easy to use. Blood tests done to confirm product use among the study participants found the preventive drug in 87 percent of the participants blood samples. Another trial in Africa is also planned to look specifically at how African adolescent girls and young women (16-21) feel about the ring.
Despite the mixed data on young women’s willingness to use the microbicidal ring, Dr. Dieffenbach, a biophysicist, maintains that DAIDS funding should only be allocated to developing prevention tools that are both long-lasting and systemic. Advocates see this decision as resulting in the defunding of microbicide research altogether. The only other potential funder for the field would be private, corporate interests. Unfortunately, the available evidence demonstrates that that this expectation is not at all realistic.
At its highest level (in 2006-07), commercial investment comprised 2 percent of all funding for microbicide research, and development and came from small biotech companies, not pharmaceutical corporations. By 2016, commercial interests were providing 0.2 percent of all resources for microbicide development. Without public support, and specifically without DAIDS funding, microbicide research and development will likely stall. This will waste 25 years of labor, amassed expertise, and investment that have brought the field to this present cusp of success, as well as the opportunity to put HIV prevention into women’s hands.
DAIDS’ focus on long-lasting methods overlooks the fact that effective microbicides are right around the corner and no injectable PrEP (which would likely require six clinic visits per year) or HIV vaccines have proven levels of effectiveness. Further, it ignores the great lesson of contraception: that different people want different methods. When people have a range of birth control choices (pills, implants, rings, injections, intrauterine devices, and so on) available to them, the number of unintended pregnancies goes down. One size does not fit all, especially in terms of personal protection. We can’t end AIDS by ignoring that lesson.
Between Now and November 30: Take Action
DAIDS has provided an opportunity for the public (in the United States and internationally) to submit comments between now and November 30. These comments go straight to DAIDS and they make a difference!
To enter your comments to DAIDS about microbicide funding, go to: https://www.niaid.nih.gov/forms/refining-hiv-research-enterprise-response-form
Here are some points to keep in mind:
- The United States has been, by far, the world’s strongest funder for microbicides research to date. If that stops in the next funding cycle, the chance to finish development of microbicides that could save millions of lives will be lost.
- Men who have sex with men in a wide range of countries and young women, especially those in southern Africa, are two key populations at very high risk of HIV contraction. If we can reduce their vulnerability to HIV, we may be able to turn the tide of AIDS. Both populations have expressed the desire for microbicides and a willingness to use them. Their needs are immediate, urgent, and ongoing.
- A multi-purpose vaginal ring is already in development that would provide women with contraception and HIV protection—an enormous benefit, especially for young women. The United States must not stop now and miss the chance to put these kinds of tools into women’s hands!
- Several rectal microbicide products are now being tested for their feasibility and safety. With so much money and time already invested, it would be financially wasteful not to finish testing these candidates to find out if one or more of them works for rectal protection.
You can also sign on to an international community letter to DAIDS on this issue by clicking on this link. Signers (organizations and individuals) from all nations are welcome!
The level of alarm about this change in direction has even roused Congress members’ attention. Rep. Jan Schakowsky (D-IL) has initiated a “Dear Colleague” letter inviting her colleagues to join her in signing to, “Support Microbicides as an NIH and NIAID Research Priority.” Please speak out with us on this urgent issue. Together, we can be heard.
For more information on this issue, please visit http://rectalmicrobicides.org/save-microbicide-research-and-development/.
By Anna Forbes