In order to keep an HIV infection at bay, those affected usually have to swallow medication every day. If you neglect to take it, the virus can multiply in your body and cause AIDS. Now researchers have developed an injectable gel that releases an HIV drug over several weeks. In mice, a single injection was enough to maintain consistently high levels of the active ingredient for 42 days. Studies on humans are still pending.
Anyone who is infected with HIV retains the virus in their body for life. However, antiretroviral drugs can prevent the virus from multiplying and leading to AIDS. To do this, however, those affected must follow a strict intake schedule throughout their lives and take the medication once or several times a day, ideally always at the same time. This not only limits the quality of life of those affected, but also means that many people do not stick with therapy long-term. Researchers are therefore looking for solutions that enable treatment without swallowing pills every day.
Gel made from active ingredient molecules
A team led by Han Wang from Johns Hopkins University in Baltimore, Maryland, has now developed an injectable solution that forms a gel in the body and delivers the HIV drug lamivudine over several weeks. “The biggest challenge in HIV therapy is the need for lifelong treatment,” says Wang’s colleague Honggang Cui. “Reducing dosing frequency may help patients adhere to treatment regimens.”
Lamivudine has traditionally been taken in tablet form. Wang and his team modified the drug molecules so that they form an injectable solution and assemble into filaments several micrometers long in the body. These filaments are able to bind water, creating a gel-like consistency that resembles biological tissue. “The most exciting aspect of these gel filaments is that they are made entirely of the therapeutic agent itself,” says Cui. The individual active ingredient molecules are gradually released from the gel, so that a consistently high drug level in the blood is maintained over a longer period of time.
Consistent release over six weeks
To test how long the active ingredient is released in a therapeutically relevant concentration, the researchers injected the solution under the skin of mice. “The experiments confirmed that the solution is easy to inject, quickly forms a hydrogel in the body and releases the active ingredient over a long period of time,” writes the team. The active ingredient was detectable in the blood of the mice at a therapeutically effective concentration over 42 days. “Maintaining the high drug concentration in plasma over 42 days is very impressive,” says Cui. “But we hope that this will be possible for longer in the future.”
The researchers also want to work on making other HIV medications available as hydrogels. Lamivudine alone often loses its effectiveness after a short time because the virus quickly develops resistance to the active ingredient. It is therefore combined with other medications in common therapy regimens. “Our technology offers a platform that can also be programmed so that several different medications can be administered at the same time,” explains Wang’s colleague Charles Flexner.
Also against hepatitis B
From the researchers' point of view, one advantage of lamivudine is that it not only works against HIV, but also against hepatitis B. “Especially in Africa and Asia, many people infected with HIV also suffer from hepatitis B,” says Flexner. The therapy could therefore help against both diseases at the same time. Additional active ingredients against hepatitis B could also be added. “We assume that our results will make an important contribution to the development of long-acting injectable active ingredients,” write the researchers. “The presented antiretroviral hydrogel is very promising for improving HIV treatment.”
In the long term, it is also conceivable that risk groups could use the hydrogel as a preventative measure to avoid infection with HIV. However, the hydrogel has not yet been tested on humans. It remains to be seen whether it is actually able to keep the virus in check in the bodies of people infected with HIV.
Source: Han Wang (Johns Hopkins University, Baltimore, Maryland) et al., Journal of the American Chemical Society; doi: 10.1021/jacs.3c05645