Raltegravir plus abacavir/lamivudine in virologically suppressed HIV-1-infected patients: 48-week results of the KIRAL study

Abstract

BackgroundLong-term combination antiretroviral therapy often results in toxicity/tolerability problems, which are one of the main reasons for switching treatment. Despite the favorable profile of raltegravir (RAL), data on its combination with abacavir/lamivudine (ABC/3TC) are scarce. Based on clinical data, we evaluated this regimen as a switching strategy.DesignMulticenter, non-controlled, retrospective study including all virologically suppressed HIV-1-infected patients who had switched to RAL+ABC/3TC.MethodsWe evaluated effectiveness (defined as maintenance of HIV-1-RNA <50 copies/mL at 48 weeks) safety, tolerability, laboratory data, and CD4+ count at week 48 of this switching strategy.ResultsThe study population comprised 467 patients. Median age was 49 years (IQR: 45–53). Males accounted for 75.4%. Median CD4+ count at baseline was 580 cells/μL (IQR, 409). The main reasons for switching were toxicity/tolerability problems (197; 42.2%) and physician’s criteria (133; 28.5%). At week 48, HIV-1 RNA remained at <50 copies/mL in 371/380 (97.6%; 95%CI: 96.4–99.0) when non-virological failure was censured. Virological failure was recorded in 1.9% patients and treatment failure in 20.5% of patients (96/467 [95%CI, 16.9–24.2]). The main reasons for treatment failure included switch to fixed-dose combination regimens (31; 6.6%), toxicity/poor tolerability (27; 5.8%), and physician’s decision (17; 3.6%). A total of 73 adverse events were detected in 64 patients (13.7%). These resolved in 43 patients (67.2%). Of the 33 cases related or likely related to treatment, 30 were Grade-1 (90.9%). CD4+ count and renal, hepatic, and lipid profiles remained clinically stable over the 48 weeks.ConclusionsOur findings suggest that RAL+ABC/3TC could be an effective, safe/tolerable, and low-toxicity option for virologically suppressed HIV-1-infected patients.

Efficacy and safety of abacavir/lamivudine with raltegravir in treatment-experienced and treatment-naïve patients with HIV-1 infection: an observational, retrospective, multi-centre study

“…9 The KIRAL study, a recent multicentre, non-controlled, retrospective study, assessed the efficacy of ABC/3TC plus RAL in 380 virologically-suppressed patients, showing a high virological suppression rate at 48 weeks (97.6% of subjects with HIV-RNA <50 copies/mL). 10 With regard to the metabolic profile, as already mentioned, we observed a significant difference in triglycerides between mean values before the switch to ABC/3TC plus RAL and mean values at the latest measurement. We have therefore differentiated subjects according to the previous regimen: in the patients who switched from PI-based regimens, we observed a significant improvement of the lipid profile, particularly a decrease of total cholesterol and triglycerides.…”

“…Similarly to our study, in other studies the switch to ABC/3TC plus RAL led to an improvement in lipid levels and liver function, particularly if the previous regimen contained a PI. 6,7,10,11 In the treatment-naı¨ve group, all five patients achieved viral suppression at the latest measurement, suggesting the efficacy of ABC/3TC plus RAL among treatment-naı¨ve patients. Three patients had pretreatment viral loads > 100,000 copies/mL, and all of them achieved viral suppression.…”

“…9 The KIRAL study, a recent multi-centre, non-controlled, retrospective study, assessed the efficacy of ABC/3TC plus RAL in 380 virologically-suppressed patients, showing a high virological suppression rate at 48 weeks (97.6% of subjects with HIV-RNA <50 copies/mL). 10…”

Effectiveness of integrase strand transfer inhibitors among treatment-experienced patients in a clinical setting

“…Clinical trials have demonstrated that patients with suppressed viral loads maintain high rates of virologic suppression after switching to INSTI-containing regimens. 5,14,15 Some observational studies have also shown good virologic outcomes in suppressed patients switching to RAL, [16][17][18] one study in patients switching to EVG, 9 and one in patients switching to DTG. 19 One cohort study reported low failure rates over two years after switching while suppressed to an INSTI-based regimen, including RAL, DTG, and EVG, though it did not compare INSTI agents.…”

Efectividad y seguridad del cambio a esquema basado en raltegravir en pacientes con infección por VIH dislipidémicos bajo terapia anti-retroviral en Fundación Arriarán

“…Llama la atención que, pese a la mejoría significativa del perfil lipídico, sólo una proporción menor de los pacientes logró normalizarlo. El efecto de la modificación de la TAR a RAL sobre el perfil lipídico de los pacientes con supresión virológica ha sido menos consistente en los estudios de cohorte "de la vida real" (ECVR) que han sido publicados [14][15][16][17] . Los cambios reportados en los TG van desde descensos no significativos (estudios ORASWIRAL 15 y KIRAL 16 ) hasta caídas de 26,1% del valor basal 17 .…”