Abstract
Long-acting parenteral drug delivery is an established and widely accepted solution to the problem of poor adherence when daily oral medications are used to treat or prevent chronic medical conditions. Poor adherence to oral formulations remains a major barrier to successfully treating or preventing HIV, tuberculosis (TB), and viral hepatitis. The uptake of long-acting formulations developed for these infections is uncertain, despite their promise. This review addresses the current state of development of long-acting and extended-release approaches to HIV, TB, and viral hepatitis in the context of creating market demand for such products. Two nanoformulated long-acting injectable antiretroviral compounds, cabotegravir and rilpivirine, recently completed Phase 2 clinical trials demonstrating safety, tolerability, and antiretroviral activity, and should be available in high income countries following completion of ongoing Phase 3 trials. Long-acting polymer implants of the antiretroviral nucleosides tenofovir alafenamide and 4'-ethynyl-2-fluoro-2'-deoxyadenosine are being tested in animals and should soon enter human studies; tenofovir alafenamide also has activity against hepatitis B virus. Long-acting versions of several broadly neutralizing monoclonal antibodies are in advanced clinical trials for HIV prevention and treatment. Long-acting formulations for TB are in preclinical development. There is no evidence that comparable formulations for viral hepatitis are being developed at present. Long-acting and extended release formulations are promising approaches to the treatment and prevention of common infectious diseases, but their availability is limited at this time. These products hold great promise for the global control of important human infections. Based on experience with other diseases, it is likely that their use will become more widespread if they are cost competitive with generic oral formulations.
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