Introduction: Treatment of HIV infection has consistently evolved in the last three decades. A steady improvement in efficacy tolerability, safety, and practical aspects of treatment intake has made HIV infection much easier to manage over the long term, and in optimal treatment conditions the life expectancy of persons living with HIV infection now approaches the values of the general population. The last category of antiretrovirals to be fully developed for clinical use is the one of strand-transfer integrase inhibitors (INSTIs). Areas covered: In this review, the evolution of the knowledge on INSTIs use in the clinical setting is reviewed, analyzed, and interpreted. Emphasis is placed on the properties possibly accounting for several superiority results achieved by INSTIs in non-inferiority designed comparative clinical trials, which led to their inclusion as first line options in all versions of HIV therapeutic guidelines. Expert commentary: Some unprecedented clinical-pharmacological properties of INSTIs, such as their rapid and sustained action against HIV replication, the optimal tolerability and safety profile and a clinically proven robust genetic barrier are the main factors justifying the successful clinical use of INSTIs. Based on these unique features, novel INSTIs-based treatment modalities are being developed, including the reduction of antiretroviral regimens to two drugs only.
Keywords: HIV infection; clinical pharmacology; integrase strand-transfer inhibitors; pharmacodynamics; pharmacokinetics.