Long-Acting Antiretroviral Formulations: A New Perspective Aimed to Improve Adherence to HIV Therapy

Despite multiple therapeutic options available to HIV patients that include several classes of antiretrovirals (ARVs) the HIV pandemic has reportedly affected more than 35 million patients in 2014. Optimizing treatment success requires new ARV molecules and an adherence to treatment above 95%. Long-acting ARV formulations that could be administered every 1-3 months offer a promising solution to these two priorities.

Long-acting ARVs are available as nanoformulations, achieve high intracellular concentrations and a good tissue distribution. Thus, long-acting ARVs could be used for both pre and post-exposure prophylaxis as well as for the treatment of the HIV infections. Moreover, long-acting ARV could significantly increase adherence to treatment while also displaying fewer adverse effects and offering an economic alternative in non-adherent HIV infected patients failing on other ARV therapies. Still, there is insufficient data on these formulations and further studies on HIV patients are needed to assess issues related to the pharmacokinetics, safety, tolerance, efficacy and potential combinations with other ARV drugs. The longacting ARV candidates in the latest stages of development are GSK744 -an Integrase Strand Transfer Inhibitor and TMC278 -a Non-nucleoside Reverse Transcriptase Inhibitor.

The current chapter reviews the results of various trials on GSK744 and TMC278 longacting ARV candidates, their advantages and disadvantages compared with the ARV drugs already in use as well as the possibility to comply with HAART principles thus becoming a reliable alternative to current ARV drugs.

Keywords: Adherence, antiretroviral agents, antiretroviral regimen, antiretroviral resistance, antiretroviral efficacy, side effects, cabotegravir, clinical trials, GSK1265744, HAART, HIV, human studies, once-daily formulation, long-acting drug, nanoformulations, parenteral antiretrovirals, pharmacokinetics, prophylaxis, rilpivirine, TMC278 LA