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| |  Switch From a Boosted PI to Raltegravir Maintains Virological Control, Lowers Plasma Lipids: Presented at AIDS 2010 By Evelyn Harvey VIENNA -- July 27, 2010 -- Raltegravir can replace a boosted protease inhibitor (PI) in antiretroviral therapy regimens for HIV-infected patients who have achieved stable virological control, according to results from the Switching From PI to RALtegravir in HIV Stable Patients (SPIRAL) study, presented here at the 18th International AIDS Conference. Substitution with raltegravir improves lipid profiles and may reduce cardiovascular risk, added lead investigator Esteban Martinez, MD, Hospital Clinic, Institut d'Investigations Biomediques August Pi i Sunyer, University of Barcelona, Barcelona, Spain, speaking here on July 20, 2010. The 48-week SPIRAL study aimed to demonstrate the non-inferiority of raltegravir in terms of virological control and tolerability, compared with protease inhibitors. Two hundred eighty-six adults infected with HIV-1 were recruited, of whom 273 were included in the study analysis. At baseline, all patients had maintained a viral load of <50 copies/mL of plasma HIV RNA for at least the previous 6 months on a ritonavir-boosted PI-based therapy. Subjects were assigned to switch to raltegravir (n = 139) or to continue with the boosted PI regimen (n = 134). In each arm, 52% of patients continued on an emtricitabine/tenofovir DF backbone, 20% on abacavir/lamivudine, and 28% on other regimens. The primary endpoint was the proportion of patients who were free of treatment failure, defined as discontinuation, virological rebound, AIDS-defining illness, or death, at 48 weeks. The Data and Safety Monitoring Board recommended continuing the SPIRAL study after an unplanned analysis following the interruption of the SWITCHMRK studies. The study was powered to show non-inferior efficacy of raltegravir-based therapy with a margin of -12.5%. At 48 weeks, 89% of patients who switched to raltegravir and 87% of those continuing on PIs remained free of treatment failure (difference 2.6%; 95% confidence interval [CI] -5.2% to 10.6%). In the raltegravir group, 97% of patients remained free of virological failure, compared with 95% in the boosted PI group (difference 1.8%; 95% CI -3.5% to 7.5%). In both groups, around 50% of patients with virological failure had prior suboptimal antiretroviral therapy or virological failure, or resistance mutations. Significant decreases in plasma lipids, including total cholesterol, triglycerides, and low-density lipoprotein cholesterol (all P < .001), were observed after switching to raltegravir, relative to continuing a ritonavir-boosted PI regimen. Severe adverse events and study-drug discontinuations due to any adverse event in the raltegravir and protease-inhibitor groups occurred in 4% and 2% of patients, respectively. Comparing data from SPIRAL with pooled results from the SWITCHMRK studies, Dr. Martinez noted that response rates for raltegravir in the SPIRAL study were substantially higher. The SWITHCMRK trials, however, established a much shorter period of stable virological control prior to switching from protease inhibitors to raltegravir, which may account for the difference. "In patients with sustained virological suppression on boosted protease inhibitor-based therapy, switching from protease inhibitors to raltegravir demonstrated non-inferior efficacy and resulted in a more favourable lipid profile at 48 weeks than continuing on protease inhibitors," concluded Dr. Martinez. The SPIRAL results extend the treatment options for long-term virological suppression in patients with HIV-1, although further refinements will doubtless emerge over subsequent studies and through open-label data.
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