Safety and efficacy of a raltegravir‐based dual antiretroviral therapy in clinical practice

Abstract

Background: HAART has revolutionized HIV disease management and increased life expectancy for most HIV-infected individuals on treatment. A nucleoside/tide reverse transcriptase (NRTI) inhibitor backbone is a recommended component of standard first-line HAART. Nevertheless, NRTI-sparing alternatives are warranted in order to reduce long-term toxicities in many patients (pts). Aim of the study was to evaluate safety of raltegravir-based dual antiretroviral therapy (DUAL) in a clinical practice setting. Methods: All pts on DUAL regimen followed at our outpatient HIV service on May 31st 2012 were recruited. Their clinical files were retrospectively studied. Collected data included: demographics, CDC staging, reason to DUAL switching, cholesterol (total and HDL), creatinine, CK, CD4+ count and HIV RNA were recorded at switch and every six months after for the first year. Change in CD4 count after the switch was evaluated by Student t-test. Results: The cohort included 55 pts (27 M); mean age was 54 years (38-72). HIV infection was acquired through: injective drug abuse (25), unprotected homosexual (24) and heterosexual (16) intercourse. CDC staging was: A=16, B=26, C=13. Mean previous treatment regimens were 4. At time of study pts had been on DUAL regimen for 23 months. They had been switched to DUAL therapy for: drug resistance (14; 25.5%) (DRR) or drug toxicity (41; 74.5%). The most frequently associated drug was darunavir/rtv (19; 34.5%), followed by atazanavir (13; 23.6%; 5 were unboosted); lopinavir/rtv (12; 21.8%), and NVP (11; 20%). DRR pts presented at baseline a mean viral load of 40,153 copies of HIV-RNA/ml; after at 12 months all but 3 showed undetectable (<40 copies) viral load and a mean CD4 gain of 142 cells/ml. Pts switched to DUAL for toxicity presented persistent undetectable viral load and a mean CD4+gain of 94 cells/ml. The observed CD4+increase in both groups (DRR and toxicity) presented a statistical significance (p<0.01). Total and HDL cholesterol, and creatinine did not present significant variations. CK remained stable and no toxicity episode was observed. Conclusion: DUAL approach showed good safety and also remarkable results in terms of viral suppression and immunological recovery. Notwithstanding the potential low genetic barrier of some combinations (e.g. NVP+RAL) this strategy demonstrated to be effective. The long term reliability of DUAL should be confirmed by studies with a longer follow up and a wider sample.