For people at high risk of contracting HIV, missing doses of their day by day HIV prevention pills can have big consequences. In some cases, missing a pill can result in lack of protection against the virus.
Since 2017, the lab of Rahima Benhabbour, PhD, MSc, associate professor within the UNC/NCSU Joint Department of Biomedical Engineering, has been working with a research team on the Centers for Disease Control and Prevention (CDC) consisting of J. Gerardo García-Lerma, MSc, PhD, Ivana Massud, PhD, and Charles Dobard, PhD and others at UNC, to develop an injectable implant that may release HIV pre-exposure prophylaxis (PrEP) medications into the body for a protracted time period.
Their latest research, published in Nature Communications, shows that the team’s latest formulation can provide as much as six months of full protection.
That is the primary time we showed 100% protection against multiple virus challenges in a macaque model of PrEP over an prolonged time period. Our goal with this technology is an once or twice-yearly injection that might be self-administered.”
Rahima Benhabbour, PhD, MSc, Associate Professor, UNC/NCSU Joint Department of Biomedical Engineering
Day by day oral PrEP has been shown to be highly effective in stopping HIV infection, but it surely is handiest when taken consistently. Adherence to the day by day regimen might be difficult, particularly amongst young sub-Saharan African women due to high stigma. Consequently, researchers are developing long-acting PrEP drugs and technologies that do not have a day by day burden.
Benhabbour has been specializing in refining the formulation — the fabric contained within the injection. Their past research produced a formulation that consists of a solvent system, a biodegradable polymer, and the drug of interest. Cabotegravir is an integrase inhibitor that was chosen by the researchers for the study
Once the formulation is injected into the skin, the solvent components are absorbed by the encompassing environment. What’s left behind is a solid implant of the biodegradable polymer and the drug. The drug is released through two mechanisms: diffusion and degradation of the polymer. The important thing aspect of this formulation is to slowly release the drug over time, while still having a high enough concentration to supply full protection.
Although the technology is sound, past iterations of the formulation weren’t reaching the drug plasma levels the researchers wanted. They might not reach the established benchmark for antiretroviral drugs to attain protection against seminal HIV (SHIV) infection in macaques. So, they re-engineered the formulation, and their results exceeded expectations on multiple fronts.
The primary success involved a significantly low burst release of the drug.
“The burst release was the bottom we have ever seen with any drug that was formulated on this injectable,” said Benhabbour. “It is vital to take care of a low burst release upon injection to mitigate safety concerns resulting from exposure to high drug levels if the burst is simply too high. The low burst also allows the drug to last more within the body, provided that initial drug levels are enough to attain protection.”
One other profit to this formulation is that the small implant might be removed if one must terminate the treatment resulting from any adversarial reactions or a breakthrough infection. Their most up-to-date experiments saw a rapid decrease of the drug’s levels within the plasma once the implant is faraway from the body.
For Benhabbour, “the cherry on top” was the efficacy results from the macaque challenges. Macaques, which have similar immune systems to humans, were challenged with simian HIV by the rectal route. Rectal exposure is one of the crucial efficient routes of HIV infection.
Over the study, 6 macaques were exposed to SHIV weekly over several months. Despite a cumulative of 38 challenges, not one of the macaques contracted simian HIV.
When the dosage was determined to be effective within the macaques, it was as much as Mackenzie Cottrell, PharmD, MS., assistant professor within the Division of Pharmacotherapy and Experimental Therapeutics on the UNC Eshelman School of Pharmacy, to model the length of protection in humans. Her model estimated that the identical dose given to the macaques would stay within the human body for five.6 months.
The subsequent step of their research is to adapt the technology for human use. To achieve this, Benhabbour and the CDC team will acquire funding to support IND-enabling studies prior to translation to human clinical trials.
“UNC is home of world class experts in clinical trials for HIV prevention,” said Benhabbour. “It could be terrific to reap the benefits of this in-house expertise in clinical trials to guage our technology.”
Source:
University of North Carolina Health Care
Journal reference:
Young, I.C., et al. (2023) Ultra-long-acting in-situ forming implants with cabotegravir protect female macaques against rectal SHIV infection. Nature Communications. doi.org/10.1038/s41467-023-36330-5.