Strategies for optimizing antiretroviral treatment in virologically suppressed patients are
still a major challenge in the field of HIV. These strategies include improving the toxicity
and tolerability of drugs in the short and long term, such as replacing toxic agents with
safer ones or reducing the number of drugs in the combination. Tenofovir alafenamide (TAF) is
a novel prodrug of tenofovir (TFV) that is converted intracellularly to the active form,
resulting in higher concentrations of TFV diphosphate in circulating lymphocytes than those
obtained with tenofovir disoproxil fumarate (TDF). Because of these pharmacokinetic
properties, TAF results in 91% lower plasma exposure to TFV. Phase 3 studies have established
the virological noninferiority of TAF to TDF, with a lower frequency of renal and bone
adverse events. Replacing TDF with TAF may be a safe and effective option to reduce
toxicities when switching from one ARV strategy to another and, to date, could represent the
optimization of a three-drug regimen. Dolutegravir (DTG) is a potent INSTI that exhibits
rapid and potent viral load reduction and a high barrier to resistance.