What Clinicians Need to Know About the Development of Long-Acting Formulation

When thinking about the potential impact of long-acting formulations on the treatment and prevention of infectious diseases, it is important to first define what is meant by “long-acting.” In most clinical circumstances, the concept of long-acting is a relative one, based on the frequency of dosing of other treatments available for the same disease. For example, although intramuscular procaine penicillin G has an apparent half-life in plasma of 3.4 hours, and might be considered long-acting when compared to the 30 minute half-life of unaltered penicillin G, neither compares to the 672 hour apparent half-life of intramuscular benzathine penicillin G. For human immunodeficiency virus (HIV) treatments, long-acting benchmarks of ≥ 1 week, ≥1 month, and ≥ 6 months were proposed for oral, injectable, and implantable strategies, respectively, largely based on clinical benefit and patient preference.

For contemporary audiences, the term long-acting (LA) generally implies a formulation that incorporates a slow or extended release depot or device. Strategies for creating LA products could involve the unmodified original drug of interest, as is the case in the penicillin example above, or the identification of a novel small molecule or prodrug specifically designed for compatibility with LA delivery. This is how we will be using the term “long-acting” in this overview and in the accompanying Supplement of Clinical Infectious Diseases.

This Supplement was inspired by the ongoing efforts of the Long-Acting Extended-Release Antiretroviral Research Resource Program (LEAP), which is supported by grants from the National Institutes of Health (NIH). LEAP is a first-of-its-kind research support program that provides access to a broad set of scientific resources including a dedicated website, academic and industrial investigators, regulatory experts, and representatives of communities affected by HIV, tuberculosis, and viral hepatitis. This Supplement draws on the expertise of LEAP collaborators to give the clinician a comprehensive look at the current state of LA anti-infectives, including preclinical and clinical scientific topics, and regulatory, global health, and community perspectives.