Drug safety profile of integrase strand transfer inhibitors

Abstract

Introduction: HIV-1 integrase strand transfer inhibitors (INSTIs) are a novel class of antiretroviral drugs with a good safety profile. Several INSTIs have been developed clinically.

Areas covered: The purpose of this review is to examine the safety data of the three FDA-approved INSTIs: Raltegravir (RAL), Elvitegravir (EVG) and Dolutegravir (DTG). The most relevant papers related to the safety profile of integrase inhibitors were selected and summarized.

Expert opinion: INSTIs have demonstrated a favorable safety profile in Phase II and III trials. The most common clinical adverse events reported were diarrhea, nausea and headache. DTG and cobicistat, a component of Stribild^™, increase serum creatinine and decrease estimated creatinine clearance due to inhibition of active tubular secretion of creatinine without affecting renal glomerular function. INSTIs intrinsic potency, together with an outstanding safety profile, preludes an important role for these drugs to build up highly active antiretroviral treatment (HAART) in the near future.

Keywords::

• antiretroviral therapy
• dolutegravir
• elvitegravir
• HIV-1 infection
• integrase inhibitors
• integrase strand transfer inhibitors
• raltegravir
• safety
• toxicity

Declaration of interest

This work has been partially financed by grants from the Fondo de Investigación Sanitaria (08/1032, 08/1195, 09/1715, 10/2635, PI11/02512 and 13/0796), Instituto de Salud Carlos III; Fondos Europeos para el Desarrollo Regional (FEDER); Ministerio de Sanidad, Política Social e Igualdad (EC11-293); Fundación para la Investigación y Prevención del Sida en España (FIPSE 06/36572 and 06/36610); Programa de Suport als Grups de Recerca AGAUR (2009 SGR 1061); Red de Investigación en Sida (RIS): RIS-EST29 and RD12/0017/0001, RD12/0017/0005, RD17/0017/0022, RD17/0017/0029, Instituto de Salud Carlos III. Spain. F Vidal and P Domingo are supported by a grant from the Programa de Intensificación de Investigadores, Instituto de Salud Carlos III (INT11/240, INT12/282 and INT12/383). The authors do not have any conflict of interest to declare.

Notes

This box summarizes key points contained in the article.