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HomeHIV/AIDSLong-acting injectable implant shows promise

Long-acting injectable implant shows promise

An ultra-long-acting, injectable, and removable formulation of dolutegravir has proved effective in animal models.

A persistent challenge in HIV/Aids treatment and prevention is medication adherence – getting patients to take their medication as required to get the best results. Currently, a once-daily pill to prevent HIV infection is available. However, adherence to a once-daily regimen can be difficult for some people.

Researchers from the University of North Carolina School of Medicine and the US Centres for Disease Control and Prevention have published a study that reports a potentially promising remedy for this problem. The researchers developed an ultra-long-acting, injectable, and removable formulation of an antiretroviral medication called dolutegravir, and they tested the formulation’s effectiveness in animal models.

The injectable formulation includes the anti-HIV drug, a polymer, and a solvent. The three-component liquid solidifies into an implant once injected under the skin. As the polymer slowly degrades, the drug is released.

“Our study found that the formulation delivered the drug effectively, and the implants were well tolerated with little or no sign of toxicity, for five months,” said Dr Martina Kovarova, co-principal investigator of the study, assistant professor of infectious diseases at UNC-Chapel Hill, and a member of the UNC Centre for AIDS Research. “It seems to us to be the ideal drug formulation for the prevention and treatment of HIV and Aids.”

The researchers also found that the implant could be quickly and safely removed by making a small incision in the skin at the site of the implant.

Study co-author Dr Rahima Benhabbour, co-principal investigator in the study and an assistant professor in the UNC-NCSU joint department of biomedical engineering, said this means the implant could be removed if a patient has an adverse reaction, or if a patient becomes pregnant while the implant is in place. This gives it a safety advantage over other long-acting injectables that are currently in clinical trials but cannot be removed after they have been injected, according to the researchers.

“Adherence to medications is essential for treatment success. This in clearly important for HIV/Aids treatment and prevention but also for the treatment of many other chronic conditions like mental illnesses, hypertension and diabetes where this technology might have applications”, said Dr J Victor Garcia, co-investigator of the study and Oliver Smithies investigator at UNC-Chapel Hill School of Medicine.

The study was funded by a three-year, $1.8m grant from the National Institutes of Health.

Abstract
Non-adherence to medication is an important health care problem, especially in the treatment of chronic conditions. Injectable long-acting (LA) formulations of antiretrovirals (ARVs) represent a viable alternative to improve adherence to HIV/AIDS treatment and prevention. However, the LA-ARV formulations currently in clinical trials cannot be removed after administration even if adverse events occur. Here we show an ultra-LA removable system that delivers drug for up to 9 months and can be safely removed to stop drug delivery. We use two pre-clinical models for HIV transmission and treatment, non-human primates (NHP) and humanized BLT (bone marrow/liver/thymus) mice and show a single dose of subcutaneously administered ultra-LA dolutegravir effectively delivers the drug in both models and show suppression of viremia and protection from multiple high-dose vaginal HIV challenges in BLT mice. This approach represents a potentially effective strategy for the ultra-LA drug delivery with multiple possible therapeutic applications.

Authors
Martina Kovarova, S Rahima Benhabbour, Ivana Massud, Rae Ann Spagnuolo, Brianna Skinner, Caroline E Baker, Craig Sykes, Katie R Mollan, Angela DM Kashuba, J Gerardo García-Lerma, Russell J Mumper, J Victor Garcia

[link url="https://www.infectioncontroltoday.com/hivaids/long-acting-injectable-implant-shows-promise-hiv-treatment-and-prevention"]University of North Carolina School of Medicine material[/link]
[link url="https://www.nature.com/articles/s41467-018-06490-w"]Nature Communications abstract[/link]

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