New Quick-Dissolving Antiviral Insert Placed In The Rectum Could Help Prevent HIV

Preexposure prophylaxis (PrEP) pills are effective at preventing HIV infection and now there is an injectable form, Apretude (cabotegravir), that may help PrEP gain wider acceptance because it requires a shot every two months. The PrEP pills, Truvada (emtricitabine and tenofovir disoproxil fumarate) and Descovy( emtricitabine and tenofovir alafenamide) supposed to be taken daily.

Some people use the PrEP pills in an off-label way that hasn’t been FDA approved. Instead of taking the pills all the time, they take them before and after sex. The Centers for Disease Control and Prevention says that there is some evidence that off-label, “on demand” PrEP is protective for men having anal sex without a condom.

But in the absence of HIV vaccine, there is still great interest in developing HIV PrEP that would be convenient and not create continual dosing. A group of researchers is studying whether a quick-dissolving pill that is inserted into the rectum or vagina could be an effective and safe form of on-demand PrEP.

Not only would the insert be on demand but the antivirals would be localized to the site of the initial infection.

The experimental rectal insert consists of 20 milligrams of tenofovir alafenamide and 16 milligrams of elvitegravir. It was developed by Contraceptive Research and Development (CONRAD) program, a federally funded research effort focused ondeveloping microbicides, contraceptives and prevention, particular HIV prevention. The program is housed at the Eastern Virginia Medical School in Norfolk, Virginia.

Sharon A. Riddler, M.D., of the University of Pittsburgh has led research of rectal and vaginal inserts that would localize antiviral protection against HIV infection and possibly led to an on-demand prevention.

“In nonhuman primates, the insert provided protection from infection when used in the vagina and the rectum,” notes Sharon A. Riddler, M.D., a professor of infectious diseases at the University of Pittsburgh School of Medicine.

Riddler and her colleague presented findings from a study of rectal application of the insert in humans at the Conference on Retroviruses and Opportunistic Infection in Seattle in February. The researchers enrolled 23 HIV-negative participants at the University of Pittsburgh and the University of Alabama at Birmingham, six of whom were assigned female at birth. The volunteers received a single dose of the insert in the clinic. Blood, rectal fluid and rectal tissue were collected.

Seven weeks later, the volunteers returned to the clinic and were administered two of the inserts at the same time. As before, blood, rectal fluid and rectal tissue samples were collected.

Tests showed high levels of the antiviral drug in rectal tissue and fluid. Additional tests designed to mimic HIV infection suggest the inserts would be protective, with the two inserts more likely to provide protection than one.

The CONRAD program is planning a second study of vaginal application ofinsert vaginally. According to a press release from the Microbicide Trials Network, that study is designed to enroll 60 women at study sites in the U.S., Kenya and South Africa.

“The currently available PrEP options — oral pills, injections, and a vaginal ring (not approved in the US) — must be started days to weeks prior to sexual activity,” notes Riddler. The insert would be discreet. “It is small and can be carried in a pocket or purse, easy to administer, and has the potential for use in the vagina or the rectum,” she says.

Because it showed limited side effects — one mild case of anal erythema — Riddler and her colleagues believe insert would be another important choice in the HIV prevention armamentarium.

“Although the currently available products for prevention (oral, injectable, ring) have all been proven to be effective, there remain many barriers to these being used by people with the greatest need for prevention,” she said. “Additionally, even people who can access PrEP often do not because of cost, side effects, inconvenience, etc., so the continued development of a safe, discreet, on-demand, flexible option would be a great outcome of this small Phase 1 clinical trial.”