New approaches to antiretroviral drug delivery: challenges and opportunities associated with the use of long-acting injectable agents.

Research on improved treatment of HIV infection and pre-exposure prophylaxis continues. Poor adherence to treatment is the critical risk factor for virological failure and resistance development, and long-acting formulations of anti-HIV medications that need only infrequent dosing may facilitate long-term therapeutic responses. Importantly, long-acting formulations of therapeutic agents have been used to avoid missing doses or treatment fatigue to prescribed lifelong medications in a number of different medical fields, with demonstrable success. However, such formulations are associated with challenges, such as the prolongation of adverse events with the persistence of drug concentrations and concerns over the development of resistance as a result of selective pressure as drug concentrations decline. Furthermore, long-acting injectable formulations of antiretroviral (ARV) agents with infrequent dosing may be advantageous over daily oral drug intake to prevent transmission of HIV. However, the knowledge on protective drug concentrations and frequency of dosing is poor to date and implementation globally is challenging. Importantly, if nanoformulations of ARVs requiring lower drug doses become available globally, the potential for treatment cost reductions is high, as, especially in resource-limited settings, the active pharmaceutical ingredient accounts for the greater proportion of the total cost of the medicine. In conclusion, different long-acting ARVs are being studied in phase I/II for both the treatment and prevention of HIV infection, and research on administering these agents in combination has started.