A small study conducted among 23 HIV-negative men and women in the United States has found that a quick-dissolving rectal suppository - no bigger than a fingernail - that contains two antiretroviral drugs is safe, researchers announced yesterday at the Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle, United States.
The pill-like suppository combines the antiretrovirals tenofovir, alafenamide, and elvitegravir. The product is designed to be inserted in the rectum right before receptive anal sex to ward off HIV infection. Small studies like these in healthy adults are designed only to gauge whether a new medicine is safe but not whether it works. Still, scientists say the suppository released promisingly high and long-lasting doses of antiretrovirals into patients' rectal tissue and fluid.
'Exactly where needed'
As part of the study, participants began with a single dose of the suppository. Samples of their blood as well as rectal fluid and tissues were taken on the same day and for the next three days. Up to seven weeks later, people in the trial returned and were given two doses of the suppository before daily samples were again taken over the course of three days.
If future trials prove the antiretroviral-based suppository works to prevent HIV, it will become the newest form of pre-exposure prophylaxis (PrEP) or products that use antiretrovirals to prevent HIV infection.
The samples showed that the drugs stayed exactly where they are needed most to prevent HIV infection - the rectum. Although testing revealed high levels of the antiretrovirals in rectal tissue and fluids, patients' blood work showed very little of the drugs circulating throughout the body.
When the researchers took tissue samples into the laboratory and exposed them to HIV, drug levels were high enough to prevent infection, explained the University of Pittsburgh Assistant Professor of Infectious Diseases Sharon Riddler late Tuesday. These results echo the findings of previous studies in which the suppository was used vaginally.
Important themed discussion on advance in #PrEP delivery in Africa at #CROI2023 -- starting with overview of data from https://t.co/Nat7oqpe7P
-- AVAC (@HIVpxresearch) February 21, 2023
Scientists are planning to conduct a larger study of the suppository's vaginal use among 60 women across the United States, Kenya, and South Africa. It will be the first trial of the suppository in Africa.
If future trials prove the antiretroviral-based suppository works to prevent HIV, it will become the newest form of pre-exposure prophylaxis (PrEP) or products that use antiretrovirals to prevent HIV infection.
All the PrEP with none of the planning?
The suppository could fill a critical gap in PrEP, Riddler explained. It is clear from more than a decade of research that the HIV prevention pill and a new HIV prevention shot, using the long-acting antiretroviral cabotegravir works, she said, "but it's also really clear that PrEP uptake - particularly with oral and injectables - is much lower than we'd like... and this is because of cost, availability [and] desirability."
PrEP, for most people, requires advanced planning.
The soon-to-be-available dapivirine vaginal ring, for instance, can reduce a woman's risk of contracting HIV by as much as 75%. Still, a person must insert it at home monthly. The HIV prevention pill is widely available in South Africa but must be taken daily for women and transgender men. Lastly, South Africa is expected to begin piloting the HIV prevention shot this year at selected clinics and pharmacies. The injection is not a vaccine and must be administered every other month.
If the new suppository works, anally or vaginally, it could finally offer women and transgender men a PrEP option they can take just when they need it.
PrEP on demand is still a pipe dream for most
Based on current evidence, only gay, bisexual men who have sex with men and transgender women have the option of taking the pill for shorter periods of high HIV risk when having unprotected anal sex - provided they use a special "2-1-1" dosing. This type of dosing has not been shown to work for women.
Also called "PrEP on demand", this involves taking two pills two to 24 hours before sex, another pill 24 hours after sex, and a third tablet 48 hours after sex. After that, men or transgender women must continue to take one pill on each day on which sex occurs if they are being active for a few days in a row.
Although "2-1-1" dosing has been shown to be just as effective as daily pills in gay, bisexual, and other men who have sex with men, national guidelines in South Africa did not recommend it by late 2022, Paul Botha told Spotlight at the time. Botha is a site coordinator for Engage Men, which offers PrEP to gay, bisexual, and other men who have sex with men in Johannesburg. Still, Botha said, many men use PrEP on demand.
If the new suppository works, anally or vaginally, it could finally offer women and transgender men a PrEP option they can take just when they need it.
"Currently, the only on-demand product option for PrEP has only been tested in cisgender men," Riddler said. "If proven to be effective, [this new] product - which is discrete and provides protection, potentially both vaginally and rectally - would be a real game changer."
PrEP options for a real (sex) life
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New advances in HIV prevention like the injection and vaginal ring rely on long-acting antiretrovirals, but not everyone wants to commit to a year or more of these medicines circulating in their bodies. For those, a suppository like this could be the answer, said Jim Pickett, a long-time HIV activist and senior advisor with the HIV prevention organisation, AVAC.
But Pickett added that a suppository that could, one day, work both vaginally and rectally to protect against HIV also responds to the many different ways people actually have sex. "I absolutely love that it's being tested in the vagina and the rectum," he told Spotlight. "Anal sex is a human behaviour, practiced by humans of all kinds. What could be more lovely than a little insert that you can pop into the very place where all the action takes place - front or back door - and you get the peace of mind and pleasure that comes with protection," he said.
Still, an HIV prevention suppository could be years in the making.
Until then, Pickett argued countries need to do better in making a wide variety of new and proven PrEP options available to people who need them. "Unfortunately, most of our healthcare systems require people to do double back-flips and walk on their hands to gain access to any kind of healthcare, let alone HIV prevention," he said. "If you are a person of colour, or a ciswoman, or a transperson, or a queer person - your barriers are even higher. Powerful tools are worth nothing if people can't get those tools with ease," he said.
