Efficacy and Tolerability of Integrase Inhibitors in Antiretroviral-Naive Patients

Abstract

Integrase strand transfer inhibitors are a new class of antiretroviral agents recently licensed for the treatment of both naive and experienced HIV-infected patients. They inhibit the catalytic activity of the HIV-encoded enzyme integrase and prevent the integration of the HIV genome into the host cell genome, so slowing the propagation of the infection. Integrase strand transfer inhibitors cause a rapid drop in viral load, exhibit very low drug interactions (except elvitegravir/cobicistat), and have low pill burden and convenient dosing frequency. Drugs in this class have been compared to others in antiretroviral-naive patients with efavirenz and with protease inhibitors. Final results of the STARTMRK trial highlighted the better virologic and immunologic performance of raltegravir over efavirenz/emtricitabine/tenofovir disoproxil co-formulation. Raltegravir was also superior to atazanavir/ritonavir and darunavir/ritonavir in the ACTG 5257 study for the combined virologic/tolerability endpoint. Elvitegravir/cobicistat/emtricitabine/tenofovir was non-inferior to efavirenz/emtricitabine/tenofovir and to atazanavir/ritonavir plus emtricitabine/tenofovir in terms of confirmed virologic response in the GS-US-236-0102 and GS-US-236-0103 studies, respectively. Finally, dolutegravir showed non-inferiority compared to raltegravir in the SPRING-2 study and was superior to efavirenz and darunavir/ritonavir in the SINGLE and FLAMINGO trials, respectively. The aim of this review is to analyze the data on efficacy and safety of integrase strand transfer inhibitors in antiretroviral-naive HIV patients and discuss the strengths and weaknesses of drugs within this class.