HIV Prevention, PrEP Implant, May be Available Soon

Animal studies lead to a novel method for HIV prevention: a refillable implant that constantly dispenses antiretroviral drugs for up to 20 months. PrEP, an infection prevention strategy that has been around since 2010, is built around antiretrovirals.

However, the new technique, which has so far only been tested in rhesus macaque monkeys, promises an even easier way to deliver the medications. The idea is to make PrEP more accessible to patients who struggle to stick to a tablet or injection schedule.

“When taken as prescribed, PrEP can reduce the risks of HIV infection,” said study author Alessandro Grattoni, chair of the Department of Nanomedicine at Houston Methodist Research Institute.

However, the difficulty with current techniques, according to Grattoni, is that many patients skip or simply forget to take their pills on time.

“Forgetting to take oral pills or injections reduces the efficacy of PrEP, and thus increases the chances of contracting HIV,” he noted.

Furthermore, there is no mechanism to reverse a PrEP injection if a patient has a negative reaction, according to Grattoni.

He said that the implant overcomes such problems, adding that preliminary research in monkeys indicates that the technique is safe and totally protective. However, animal studies does not necessarily translate into human results.

PrEP is now only available in two forms: tablet or injectable.

Oral PrEP, which was first approved in 2012, is a single pill containing a combination of two antiretroviral drugs. The first is Truvada, which comprises FTC and TDF (emtricitabine and tenofovir disoproxil fumarate). Descovy, a second alternative, was introduced in 2016. FTC and TAF (tenofovir alafenamide) are present.

Oral PrEP, when taken daily, reduces the risk of contracting HIV from intercourse and/or injectable drug use by 99% and 74%, respectively. The only oral approach now approved by the FDA is once-daily use, while an off-label “on demand” strategy has been created for patients who choose to take PrEP tablets only before and after participating in hazardous sexual conduct.

Apretude, an injectable technique, was approved by the FDA for the first time in 2021. The injectable contains the antiviral cabotegravir and is intended for people who have a negative reaction to oral PrEP or have difficulty sticking to a once-a-day pill regimen. Injectable PrEP is initially provided in two shots, one month apart, and then once every two months after that. According to studies, the shot is somewhat more effective than the pills in HIV prevention.

Grattoni’s group set out to test PrEP delivery through medical-grade titanium implants inserted just beneath the skin.

The implants are meant to be leak and rupture resistant, and they hold approximately.57 milliliters of islatravir (ISL), an investigational antiviral drug.

Initially, just four male rhesus macaques were tested during a 20-month period.

The ISL medication was successfully “diffused” via the implant and into each animal’s bloodstream, as expected. And the researchers determined that circulating blood concentrations of ISL matched the intended protective levels seen if the monkeys had taken ISL via a weekly pill throughout the study.

The researchers next performed rectal and vaginal simian HIV exposure tests on six monkeys with implants and 12 monkeys without.

The team first discovered that all of the monkeys who received implants had protective levels of circulating ISL after only one day. Further testing found that all of the monkeys who had been implanted looked to be entirely protected against simian HIV exposure via both the rectum and the vagina, with no safety or tolerance difficulties.

Given that prior research had suggested the implant would work, “we were more excited than surprised with our results,” Grattoni noted.

“Next steps are to determine what is the lowest dose needed for continued protection, and whether the implant is effective against different routes of HIV infection, [both] sexual and injection drug users,” he said.

Grattoni said his team is now prepping for a human trial, “and we hope for clinical testing within three years. If all goes well with human trials, we think the implant could be available within five years.”

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