Clinical Pharmacology of the Single Tablet Regimen Bictegravir/Emtricitabine/Tenofovir Alafenamide in the evolving era of antiretroviral therapies.

Abstract

In this fast-evolving era of antiretroviral chemotherapy, the single-tablet regimen (STR) BIC/FTC/TAF, an oral regimen including a potent INSTI (strand-transfer integrase inhibitors) like Bictegravir plus two different NRTIs (Nucleoside Reverse Transcriptase Inhibitors), is increasingly challenged by new oral combinations. Furthermore, long-acting injectable drugs have also been developed and others are being under development. Notably, no new STR consisting of two NRTIs plus a 3rd drug like an INSTI are in the industrial pipeline. However, many People with HIV (PWH) still need potent multidrug regimens, especially those newly diagnosed with advanced HIV (defined late presenters), which represent over 50% of new infections. The asymmetrical comparison between a potent STR like BIC/FTC/TAF and new combinations is difficult to make. By comparing the STR BIC/FTC/TAF, the most representative of potent multi-drug regimens, with all approved new options, we can distinguish some features that are worthy of attention. The stronger genetic barrier and the better forgiveness resulting from BIC/FTC/TAF is self-evident, with the extra coverage here provided by the remarkable pharmacologic properties of TAF, consisting of great diffusion into target cells, long persistence at high concentration, and a much lower plasma exposure. On the pharmacokinetic side, the main difference is between oral and long-acting injectable regimens. Pk of long-acting injectables consists of a single peak (followed by a slow decrease in drug concentration), while with oral regimens daily C max - C trough fluctuations take place instead. The latter property of oral regimens should be taken into account whenever the Pk exposure is suboptimal, as it might allow inhibition of the growth of quasi-species that are less sensitive. The choice of the new combinations including long acting injectables instead of the STR BIC/FTC/TAF might be made for sure for several reasons, but compared to the past when combinations included TDF, toxicity by TAF is no longer an issue today. The size of the tablet and its net weight may be disproportional to the number of drugs, as there are multidrug regimens like the STR BIC/FTC/TAF whose weight may be lower than those of the new oral combinations INSTI-based for both naive and switching PWH. Although multi-drug regimens like the STR BIC/FTC/TAF are no longer in development, their use in clinical practice will still remain substantial for a long time and knowledge of their properties is necessary to properly select the most appropriate regimens for PWH.