Four New Approaches to PrEP in Development That Aren't a Daily Pill

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Not everyone wants to, or can, take daily emtricitabine/tenofovir disoproxil fumarate (Truvada) as pre-exposure prophylaxis (PrEP). And, as we seem to be getting closer to long-acting injectables, some advocates have questioned the feasibility of getting a shot every other month for most people. But, at the HIV Research for Prevention conference (HIVR4P) in Madrid, Spain, last week, researchers presented four new methods that are in early stages of development. If we're lucky, in a few years, there may be products that people can use just before they have sex or that are long acting and left in place for some period.

Four researchers presented their work to develop safe and effective anal/vaginal douches and inserts, implantables that are biodegradable, and vaginal rings. Here's a rundown of each method.

Kenyon Farrow is the senior editor of TheBody and TheBodyPRO. Follow Kenyon on Twitter: @kenyonfarrow.

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A Rectal Douche to Keep Clean -- and Prevent HIV

One effort in developing new tools for HIV prevention is to think of things people would normally do when preparing for sex so that they don't need to remember an extra step, such as taking a pill every day. For example, many people who engage in anal sex as the receptive partner (or "bottom") have a ritual of diet and douching to prepare for the sex act.

Ethel Weld, M.D., with Johns Hopkins University School of Medicine, and her colleagues therefore developed an anal douche with tenofovir (TFV) to assess whether the drug would concentrate in the rectal tissue or in the blood enough to provide the same protection as at least four pills of emtricitabine/TDF a week.

With 18 men who have sex with men (MSM) volunteers, they tested three different formulations of TFV (220 mg with saline, 660 mg with saline, and 660 mg with half-normal saline) in six MSM in each arm and collected blood and colorectal samples for one week.

They found that, while the blood levels of TFV were well below protective levels (as was expected since it wasn't delivered in pill form), the levels of TFV in all three groups were well above what was considered protective against HIV without the use of condoms within one-three hours of use and still above protective levels at 24 hours. It was also safe, acceptable, and well tolerated by participants.

"The prevention community is in the process of rising to meet the challenge of peoples' widely varying circumstances, preferences, behaviors, and risks contexts for HIV, and that challenge must be met with just as wide a variety of prevention technologies," said Weld. "An on-demand tenofovir douche that is not only safe and efficacious but also aligned with peoples' existing sexual behaviors, and there aligned with pleasure, is one way of meeting that challenge, and we strongly feel it should be advanced with further clinical development."

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A Biodegradable PrEP Implant That Lasts Long -- and Can Be Removed

One of the issues with taking daily PrEP is that many people forget pills and sometimes aren't able to pick up prescriptions every month. But what if PrEP could be delivered via an implant under the skin and last for months?

That's what Leah Johnson, Ph.D., researcher with RTI International, and colleagues are studying.

Their study is preclinical and not yet being tested in humans. But the goal of the study was to find the best implant design, that is, what materials to use, and to determine how the design would impact the speed with which the drug is released into the body. Researchers developed tubes out of polycaprolactone (PCL) into a biodegradable material that would also hold up in the body in case the implant needed to be removed. They used the drug tenofovir alafenamide (TAF, Vemlidy) and tested the wall thickness of the PCL encasing, as well as how sesame seed oil versus castor oil as the vehicle for delivery of the drug formulation would impact how long the implantable would last.

They found that they could sustain release of TAF at effective levels in the castor oil formulation for over four months. According to the abstract submitted to HIVR4P 2018, the researchers "are currently adjusting TAF payload, formulation, and wall thickness to demonstrate optimized implants with over six months release."

Outside this particular study, several conversations took place at the conference among advocates about how different populations, primarily cisgender women, responded to the idea of an implantable PrEP option, given many women's experiences with implant contraceptives. While there were mixed responses to the acceptability or desirability of such a product, most conversations landed with the need for multiple options.

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A Fast-Dissolving Insert That Delivers PrEP Vaginally

One current challenge for PrEP use by cisgender women is that it appears to take longer for the drug to enter vaginal tissue at protective levels than it does to enter rectal tissue. Is there a faster method of delivering PrEP vaginally that women could control?

Centers for Disease Control and Prevention researcher Charles Dobard, Ph.D., is exploring the different levels of elvitegravir/tenofovir alafenamide (EVG/TAF) needed to provide protection from HIV if delivered in a dissolvable product that could be inserted into the vagina just before sex. Only testing in macaques currently, Dobard and his team used vaginal inserts containing 8/10 mg, 16/20 mg, and 24/40 mg of EVG/TAG. Plasma, vaginal fluid, and vaginal biopsies were collected and analyzed at two, four, and 24 hours.

In the macaques, levels of EVG/TAF were found at levels good enough to prevent HIV infection in vaginal fluid and biopsies at all three time intervals, while low levels were found in the plasma as expected.

"These inserts are currently being evaluated in macaque challenge studies when applied four hours before and four hours after the exposure," said Dobard. "And CONRAD, an HIV/sexually transmitted infection research and development nonprofit, is also conducting studies in humans to look at these EVG/TAF inserts applied vaginally or rectally."

PrEP and Contraception in One Dual-Purpose Vaginal Ring

Globally, many women use some form of birth control, and for many years, researchers have been looking at ways to develop a product that could deliver both contraception and HIV prevention in one design.

Sharon L. Achilles, Ph.D., M.D., with the University of Pittsburgh and colleagues presented results from a study of two rings, one with just the PrEP drug (200 mg dapivirine) and one with both 200 mg dapivirine and 320 mg levonorgestrel (LNG, a drug for contraception), to compare safety and pharmacokinetics in 24 HIV-negative women who were randomized to using one of the rings for 14 days (although the rings are formulated to work for up to 90 days). They tested both plasma and vaginal fluid at the end of 14 days.

The product was found to be safe and well tolerated by participants. Both rings also demonstrated efficacy, in that the levels of dapivirine remained at a protective level in both rings, and LNG levels also remained high in the combined dapivirine/LNG ring.

"This brings us another step closer to potentially having an easy-to-use, women-controlled, safe and effective product for long-acting prevention of both HIV and unintended pregnancy," said Achilles.

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The Future Is in the Funding

While these studies seem to offer what many people have been asking for in HIV prevention tools (effective, discreet, easy to use, and the ability to work on-demand) more work needs to be done before any of them will be available to market. Moreover, funding is a big hurdle to doing the research necessary to prove their effectiveness in larger populations (or in humans, in some cases). At the HIVR4P conference, there was a lot of talk about the potential shutting down of the Microbicide Trials Network (MTN) at the National Institutes of Health (NIH), and what this would mean for future support of research for these trials to move forward. One journalist raised this question with a group of researchers.

"I think that NIH has decided to reduce the number of networks, which is something we disagree with in principle," responded Sharon Hillier, Ph.D., with University of Pittsburgh and MTN, who chaired the press conference where these novel PrEP studies were presented. "That said, networks don't define science; science defines science," she added. "So, we hope that we can join with our prevention partners in the [HIV Prevention Trials Network], so we can continue to move this work forward."