TAMPA, Florida — Pre-exposure prophylaxis (PrEP) has shown to be effective in many clinical and real-world studies, but concerns remain, according to research presented at the Association of Nurses in AIDS Care (ANAC) 2022 Annual Meeting.
Only about 20% of people who could benefit from PrEP use the preventative medication, for example. Another concern is adherence, as regular use generally drops off over time, rarely lasting more than a few months for most people.
Furthermore, most studies to date evaluated safety and effectiveness of PrEP options among men who have sex with men. Now the focus is increasing on other populations, including women at risk of HIV exposure.
Researchers working on new forms and formulations of PrEP are looking for ways to address those challenges.
No matter the target population, new options are needed that fit more seamlessly into people's sex lives, said Craig W. Hendrix, MD, professor and director of the Division of Clinical Pharmacology at Johns Hopkins University School of Medicine in Baltimore, Maryland.
"What I hear a lot of folks say [is] there are two or three options for PrEP, so why do we need more? We need choices that fit into a broader range of lifestyles," Hendrix said.
For example, a medically fortified douche containing PrEP might be more likely to be used by people who use a douche before or after sex on a regular basis. This is called a "behaviorally congruent" strategy, Hendrix said.
In addition to a medical douche, formulations designed to continuously deliver PrEP, such as a subdermal implant, are in the works as well.
Another option for women, the dapivirine vaginal ring, is available internationally but not in the United States. "It was withdrawn from [Food and Drug Administration] consideration by the sponsor. I think it's a huge loss not to have that," Hendrix said.
During development "frequent expulsions forced reformulation to a less stiff ring," Hendrix said. "I don't imagine that's terrific, but it shows how important it is to have something that fits the anatomy and the lifestyle."
"Currently, we have in the US three licensed, really terrific options for PrEP, and they're all for men that have sex with men and transgender women," Hendrix said.
Three Current Options
The three current PrEP regimens in the United States often go by their abbreviations: F/TDF, F/TAF, and CAB-IM.
F/TDF is emtricitabine (F) 200 mg in combination with tenofovir disoproxil fumarate (TDF) 300 mg (Truvada, Gilead or generics)
F/TAF is emtricitabine (F) 200 mg in combination with tenofovir alafenamide (TAF) 25 mg (Descovy, Gilead)
CAB-IM is cabotegravir (CAB) 600 mg injection (Apretude, GlaxoSmithKline)
There is an important distinction: daily oral PrEP with F/TDF is recommended to prevent HIV infection among all people at risk through sex or injection drug use. Daily oral PrEP with F/TAF is recommended to prevent HIV infection among people at risk through sex, excluding people at risk through receptive vaginal sex, the CDC notes.
The cost-effectiveness of the injection remains a potential issue, Hendrix said. On the other hand, "cost-effectiveness goes out the window if there is no adherence."
An Active Pipeline
There are 24 new PrEP products in development, as well as 24 other multipurpose prevention technologies (MPTs), which are combination products containing PrEP and one or two other medications.
These 48 products include 28 unique antiviral and contraceptive drugs and 12 delivery methods or formulations. "Why so many?" Hendrix asked. "Many will not make it through development."
Pills that include HIV PrEP and contraception or PrEP and sexually transmitted infection (STI) treatment are being evaluated, for example. "HIV risk, pregnancy risk, and other viral STIs overlap. Ideally, you can have one target for all three. That would increase efficiency of dosing and adherence," Hendrix said.
Dual prevention pills (DPPs) hypothetically provide HIV PrEP and contraception better than either product alone, Hendrix said. Plans are to market them as family planning or women's health products to avoid any stigma or distrust associated with HIV PrEP. An initial rollout is planned in 2024 in sub-Saharan Africa where the unmet need is highest, he added.
"Imagine how effective this could be in women in the US," Hendrix said. "My hope is fourth-quarter 2024" availability in the United States.
A way to prevent STIs and HIV in an all-in-one product "would be terrific," Hendrix said.
"I think we're going to see a lot more innovation going in that direction. The pill is close. The other things are going to be further off because the regulatory pathway is a little more complicated."
Longer Lasting Protection?
All of the innovations have gone one of two directions, Hendrix said. One direction is to make PrEP even longer acting, "so that you have even less to worry [about] in terms of adherence."
Going forward, "most of the focus has all been on continuously acting or long-active PrEP. It's getting longer and longer: we've got 2 months, and they're looking at a 6-month subcutaneous injection," Hendrix said. The investigational agent lenacapavir is in development as PrEP, as well as for HIV treatment.
"This could get us from 2 to 6 months," Hendrix said.
Some of the subcutaneous implants look as if they could provide PrEP for up to 12 months, he added. "An implant could also avoid peaks and troughs with bi-monthly injections."
The other direction is on-demand. "This is for the folks that don't want drug in their body all the time. They only want it when they need it. And a twist on that...is actually using products that are already used with sex now but medicating them."
On-demand rectal options include a medicated douche and a fast-dissolving insert or suppository.
Fast-dissolving vaginal inserts are also in development. "These inserts are small, easy to store, inexpensive, and possibly inapparent to a partner," Hendrix said.
Phase 2 studies will need to determine if these products "fit into folks' active sex lives," he said. "There's still a need for human-friendly, human-designed products."
A rectal microbicide that got as far as Phase 2 research provides a cautionary tale. The concentrations and the biology worked fine, Hendrix said. "It was a gel with an applicator, and it just was not liked by the folks in the study." He added, "Your adherence is going to be in the tank if you've got a product that people don't like to use."
Asked for her perspective on Hendrix's presentation, session moderator Rasheeta D. Chandler, PhD, RN, an associate professor at the Nell Hodgson Woodruff School of Nursing at Emory University in Atlanta, Georgia, said: "I am extremely excited because I work with cisgender women, particularly with underserved women and women of color, and there's a tendency to focus on men who have sex with men."
"I understand, because they are the population that is most affected, but Black women are also extremely affected by this disease," Chandler told Medscape Medical News.
Chandler applauded Hendrix for addressing women's health needs as well and not treating PrEP in women "as an afterthought."
"Finally, our voices are being heard that [PrEP] should be equitable across all different types of individuals who identify differently in a sexual context," Chandler said.
More work is warranted to evaluate PrEP in other populations, including transgender men and individuals who inject drugs, Hendrix said.
For more information and updates on HIV PrEP and MPTs, visit the website of the nonprofit AIDS Vaccine Advocacy Coalition (AVAC).
Hendrix has disclosed receiving research grants from Gilead and Merck. Chandler has reported no relevant financial relationships.
Based on a presentation made on November 18, 2022 at the ANAC 2022 Annual Meeting.
Damian McNamara is a staff journalist based in Miami. He covers a wide range of medical specialties, including infectious diseases, gastroenterology, and critical care. Follow Damian on Twitter: @MedReporter.
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Cite this: Future HIV PrEP Innovations Aim to Address Adherence, Women's Health, and Combination Treatments - Medscape - Nov 23, 2022.