PrEP implant could enable long-term HIV protection

For people at high risk of contracting HIV, missing doses of their daily HIV prevention pills can lead to lack of protection against the virus. The good news is that US researchers have been collaborating on an injectable implant that can release HIV pre-exposure prophylaxis (PrEP) medications into the body over a long period of time, with promising results in non-human primates.

Daily oral PrEP has been shown to be highly effective in preventing HIV infection, but it is most effective when taken consistently. Adherence to the daily regimen can be challenging, particularly among young sub-Saharan African women because of high stigma. As a result, researchers are developing long-acting PrEP drugs and technologies that don’t have a daily burden.

Since 2017, University of North Carolina (UNC) Associate Professor Rahima Benhabbour has been working with a research team at the Centers for Disease Control and Prevention (CDC) and others at UNC to develop an injectable implant that can release PrEP medications into the body. Their latest research, published in the journal Nature Communications, shows that the team’s latest formulation can provide full protection lasting several months.

The team’s past research produced a formulation that consists of a solvent system, a biodegradable polymer and the drug of interest. Once the formulation is injected into the skin, the solvent components are absorbed by the surrounding environment. What is left behind is a solid implant of the biodegradable polymer and the drug. The drug is released via diffusion and as the polymer begins to degrade. The key aspect of this formulation is that it can slowly release the drug over time, while still having a high enough concentration to provide full protection.

Although the technology is sound, past iterations of the formulation weren’t reaching the drug plasma levels the researchers wanted. They could not reach the established benchmark for antiretroviral drugs to achieve protection against seminal HIV (SHIV) infection in macaques, which have similar immune systems to humans. So they re-engineered the formulation, and their results exceeded expectations on multiple fronts.

The first success involved a significantly low burst release of the drug — “the lowest we’ve ever seen with any drug that was formulated in this injectable”, Benhabbour said. “It is important to maintain a low burst release upon injection to mitigate safety concerns due to exposure to high drug levels if the burst is too high. The low burst also allows the drug to last longer in the body, provided that initial drug levels are enough to achieve protection.”

Another benefit to this formulation is that the small implant can be removed if one needs to terminate the treatment due to any adverse reactions or a breakthrough infection. The team’s most recent experiments saw a rapid decrease of the drug’s levels in the plasma once the implant is removed from the body.

The formulation was once again tested in macaques, which were challenged with simian HIV by the rectal route — one of the most efficient routes of HIV infection. Over the course of the study, six macaques were exposed to SHIV weekly over several months. Despite a cumulative of 38 challenges, none of the macaques contracted simian HIV.

“This is the first time we showed 100% protection against multiple virus challenges in a macaque model of PrEP over an extended period of time,” Benhabbour said.

When the dosage was determined to be effective in the macaques, it was up to UNC Assistant Professor Mackenzie Cottrell to model the length of protection in humans. Her model estimated that the same dose given to the macaques would stay in the human body for 5.6 months.

The next step in the research is to adapt the technology for human use, with the aim of a once- or twice-yearly injection that could be self-administered. Benhabbour and the CDC team are now seeking funding to support IND-enabling studies prior to translation to human clinical trials.

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