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The Promise of Long-Acting Antiretroviral Therapies: From Need to Manufacture

Gendelman, Howard E., McMillan, JoEllyn, Bade, Aditya N., Edagwa, Benson, Kevadiya, Bhavesh D.
Trends in microbiology 2019 v.27 no.7 pp. 593-606
HIV infections, Human immunodeficiency virus 1, antiretroviral agents, chronic diseases, death, drugs, hydrophobicity, injection site, lipophilicity, manufacturing, surfactants, therapeutics, viral load, virus transmission
Antiretroviral therapy has transformed human immunodeficiency virus infections from certain death to a manageable chronic disease. Achieving strict adherence to drug regimens that limit toxicities and viral resistance is an achievable goal. Success is defined by halting viral transmission and by continuous viral restriction. A step towards improving treatment outcomes is in long-acting antiretrovirals. While early results remain encouraging there remain opportunities for improvement. These rest, in part, on the required large drug dosing volumes, local injection-site reactions, and frequency of injections. Thus, implantable devices and long-acting parenteral prodrugs have emerged which may provide more effective clinical outcomes. The recent successes in transforming native antiretrovirals into lipophilic and hydrophobic prodrugs stabilized into biocompatible surfactants can positively affect both. Formulating antiretroviral prodrugs demonstrates improvements in cell and tissue targeting, in drug-dosing intervals, and in the administered volumes of nanosuspensions. As such, the newer formulations also hold the potential to suppress viral loads beyond more conventional therapies with the ultimate goal of HIV-1 elimination when combined with other modalities.