Safety and efficacy of treatment switch to raltegravir plus tenofovir/emtricitabine or abacavir/lamivudine in patients with optimal virological control: 48-week results from a randomized pilot study (Raltegravir Switch for Toxicity or Adverse Events, RASTA Study)

Abstract

Background: The Raltegravir Switch for Toxicity or Adverse Events (RASTA) Study is a 2-arm randomized pilot study exploring the safety and efficacy at 48 weeks of a treatment switch to raltegravir associated with tenofovir/emtricitabine or abacavir/lamivudine in patients with regimens with optimal virological control. Methods: Patients treated with stable protease inhibitor (PI)-, non-nucleoside reverse transcriptase inhibitor (NNRTI)-, or nucleoside reverse transcriptase inhibitor (NRTI)-based regimens, with HIV-RNA levels < 50 copies/ml for ≥ 3 months and a CD4 cell count > 200 cells/μl were eligible. Enrollment of 40 patients was planned: at baseline patients were randomized 1:1 to switch to raltegravir plus tenofovir/emtricitabine (arm A) or abacavir/lamivudine (arm B). Laboratory parameters, raltegravir plasma levels, self- reported adherence, quality of life parameters, neurocognitive performance, bone composition, and body fat distribution were monitored. Virological failure was defined as HIV-RNA > 50 copies/ml on 2 consecutive determinations. Results: After 48 weeks, 5/40 (12.5%) regimen discontinuations occurred: 2 were for low-level viremia virological failure (both in arm A, at weeks 24 and 48) and 3 were for adverse events (neurological disturbances and skin rash in arm B; proximal tubulopathy in arm A). Overall, a significant CD4 increase was observed at weeks 36 and 48, and a significant decrease in total cholesterol, non-high density lipoprotein cholesterol, and triglycerides was observed at each study visit. Physical health/satisfaction in therapy scores and neuropsychological performance improved. The lumbar column Z-score improved, with no modification in other bone composition and fat distribution parameters. Conclusions: The investigated switch strategy was associated with rare virological failure. Improvements in lipid levels, quality of life measures, neuropsychological performance, and bone composition suggest good tolerability of raltegravir-based regimens.

Keywords::

• HIV
• antiretroviral therapy
• toxicity
• treatment simplification
• raltegravir

Declaration of interest: The Institute of Clinical Infectious Diseases, Catholic University of Sacred Heart, Rome, Italy, received an unrestricted grant from Merck Sharp & Dohme. The Institute of Pharmacology, Catholic University of Sacred Heart, Rome, Italy, received a grant from Merck Sharp & Dohme in support of a local IISP (#34876) entitled “Therapeutic drug monitoring (TDM) of the integrase inhibitor MK-0518”. MF has received speakers’ honoraria from Abbott Virology, Merck Sharp & Dohme, and Janssen-Cilag. MC has been a paid consultant for Merck Sharp & Dohme, Italy and was employed by Bristol-Myers-Squibb, Italy from May 10, 2010 to February 28, 2011. RM has received speakers’ honoraria from Abbott, Gilead and Bristol-Meyers Squibb. RC has been advisor for Gilead and Janssen-Cilag, has received speakers’ honoraria from ViiV, Bristol-Myers Squibb, Merck Sharp & Dohme, and Janssen-Cilag, and has received research support from “Fondazione Roma”. ADL has received speaker's honoraria and fees for attending advisory boards for ViiV Healthcare, Gilead, Abbott Virology, Janssen-Tibotec, Siemens Diagnostics and Monogram Biosciences. SDG has received speakers’ honoraria and support for travel meetings from Gilead, Bristol-Myers Squibb, Abbott, Boehringer Ingelheim, Janssen-Cilag, and GlaxoSmithKline. All other authors have nothing to declare.