HIV therapies have come a long way since the 1980s, when the first antiretroviral therapy, AZT, was approved by the FDA. Patients have gone from having to take multiple pills a day to two or even fewer, thanks to the approval of long-acting injectable drugs administered just once a month.
Now, in a study published Sept. 25 in the Journal of the American Chemical Society, a team led by biomedical engineers at Johns Hopkins University School of Medicine reported that they have developed a new injectable hydrogel that maintains plasma concentrations of a common HIV drug, lamivudine—also known as 3TC—for six weeks in mice. Eventually, the scientists hope to add other HIV drugs given alongside 3TC to the same hydrogel, so they can all be administered at once.
“This is a novel way to deliver anti-HIV meds, and this platform has the advantage that a single polymer can be programmed to deliver several different drugs simultaneously,” study co-author Charles Flexner, M.D., said in a press release.
The hydrogel is a new formulation of the drug itself as opposed to being a “carrier” or a separate delivery system. It’s designed to be injected under the skin, where it self-forms into a sort of storage site that gradually dissipates into the bloodstream. After tweaking the polymer to maximize its longevity, the researchers injected it into the backs of five adult male mice, which were compared with a second group that received injections of 3TC without the hydrogel.
While the drug was undetectable by Day 3 in the controls, concentrations continued to rise in the experimental group until Day 7, then remained at levels high enough to suppress HIV for another 36 days. Even at Day 49, the drug was still at high levels in tissues like the liver, spleen, lymph nodes, lungs and kidneys.
The researchers are now looking at ways to add other drugs commonly given alongside 3TC to the hydrogel. They also think they can get the dosing intervals to last “several months or even longer” by optimizing the design of the hydrogel and drug dosage, according to the paper. This could give it potential utility as an HIV prophylaxis, the press release noted.
“Keeping the high drug levels in plasma for 42 days is very impressive,” lead researcher Honggang Cui, Ph.D., said in the release. “But in the future, we hope it will be even longer.”
Meanwhile, the researchers also noted that because lamivudine is used to treat hepatitis B, the new hydrogel has potential against that virus as well. Given that hepatitis B is a common co-infection with HIV, this is one advantage the drug has over currently approved injectable HIV therapies, which treat that virus alone, Flexner said in the release. The hydrogel can already be modified to hold the drug tenofovir, the standard-of-care therapy for chronic hepatitis B and another medication in the HIV treatment and prevention arsenal.
“The primary challenge in HIV treatment is the need for lifelong management of the virus,” Cui said in the release. “This new molecular design shows us a future in which drug hydrogelation can do that to improve HIV treatment.”