A Further Step Toward Long-Acting Injectable HIV Drugs

One of the biggest barriers for people at risk of acquiring HIV, or who have already been diagnosed with it, is the burden of pill taking. Although pre-exposure prophylaxis, or PrEP, is offered as a once-a-day regimen, as are various antiretroviral therapy (ART) regimens, accessibility to these drugs, the stigma of HIV, and simple human error can present significant obstacles to adherence. New research using mouse models shows a pathway toward streamlining HIV prevention and treatment into an injectable implant that can deliver multiple drugs continuously for months or even a year, thus dangling the possibility of an annual or biannual shot instead of a daily pill.

A team of investigators at the University of North Carolina at Chapel Hill’s UNC/NCSU Joint Department of Biomedical Engineering; UNC Eshelman School of Pharmacy; and UNC’s International Center for the Advancement of Translational Science, part of the Division of Infectious Diseases at the Center for AIDS Research at UNC’s School of Medicine, have demonstrated the efficacy of a single injectable implant for delivery of 1 or more drugs.

The injection consists of a solvent, a polymer, and the drug or drugs prescribed. Once injected under the skin, these elements combine to become a solid mass. “The solidification is relatively fast, and it occurs in a matter of hours or a few days,” Martina Kovarova, PhD, associate professor of medicine and J. Victor Garcia, PhD, professor of medicine, who are in the Division of Infectious Diseases and are 2 of the authors of the study, told Contagion®. “It allows for the formation of a depot from which [the] drug[s] can be slowly released with appropriate kinetics. In the models used in this manuscript, the formulation is clearly visible and palpable underneath the skin. This was done by design to facilitate experimentation and analysis.”

The implant’s kinetics include an initial burst release, in which the drugs are quickly released during the first day or 2 after implantation. The drugs then continue to be released as the solvent diffuses and the polymer degrades. When all of the drugs are dispensed, the residual matter fully absorbs into the body.

Six different ART drugs were tested in various combinations. The investigators looked at the drugs’ solubility, density, viscosity, stability, and activity after having been stored for 6 months and then solidified. All of their physical and chemical properties were retained during the study, and drugs were released from the implant for periods of time ranging from 1 month to 1 year.

While other researchers have been working to develop injectable antivirals, the UNC investigators’ long-acting implant is different because it can be quickly removed, such as in the case of an adverse reaction or pregnancy, rendering the drugs undetectable in the body after 1 week. The implant also is adjustable, with the ability to alter the amounts and kinds of polymers and solvents to fine-tune the kinetics of the drug release.

“The long-term goal of this work is to set a framework for the development of ultra-long-acting formulations that could provide appropriate coverage for a target of 6 months or longer to improve adherence and to facilitate compliance,” said Kovarova and Garcia.

The investigators said further testing using larger animals is needed to determine whether their approach can be scaled up for use in humans; the timeline for this is unknown.