Tolerability of HIV integrase inhibitors

Lee, Frederick J.; Carr, Andrew

doi: 10.1097/COH.0b013e328356682a
INTEGRASE INHIBITORS: Edited by Charles Hicks and Esteban Martinez

Purpose of review: This review discusses the available safety data for three integrase strand transfer inhibitors (INSTIs) – raltegravir, elvitegravir and dolutegravir – derived from studies in both HIV-infected and HIV-uninfected cohorts.

Recent findings: Phase 2 and 3 clinical trials show that all three INSTIs are well tolerated in treatment-naive and treatment-experienced patients with headache and gastrointestinal effects being the most commonly reported adverse events. Other nervous system (including neuropsychiatric) effects are often reported with INSTIs but are milder and less frequent than with efavirenz. Limited data suggest that effects upon lipid metabolism with raltegravir and dolutegravir are favourable compared with efavirenz and protease inhibitors, with more variable findings for elvitegravir because of coadministration with the boosting agent cobicistat. Cobicistat and dolutegravir have effects upon proximal renal tubular function causing mild-to-moderate creatinine elevation. Rare and severe events possibly related to INSTIs include systemic hypersensitivity reactions and rhabdomyolysis.

Summary: INSTIs are an important recent addition to the antiretroviral armamentarium, with good short-term and medium-term safety. Long-term data from ongoing clinical studies are needed for a definitive assessment of their safety profile.

HIV, Immunology and Infectious Diseases Unit and Centre for Applied Medical Research, St. Vincent's Hospital, Sydney, New South Wales, Australia

Correspondence to Dr Frederick J. Lee, St. Vincent's Centre for Applied Medical Research, Level 4, Xavier Building, St. Vincent's Hospital, 390 Victoria Street, Darlinghurst, New South Wales 2010, Australia. Tel: +61 2 8382 3599; fax: +61 2 8382 2090; e-mail: flee3@stvincents.com.au

© 2012 Lippincott Williams & Wilkins, Inc.