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| |  Switching HIV-Infected Patients to Raltegravir Improves Lipids, But With Lower Virological Control NEW YORK -- January 12, 2010 -- Patients with HIV who are stable on a regimen of lopinavir-ritonavir can reduce their levels of blood fats by switching to raltegravir; however, switching also leads to a lower proportion of patients reaching the target for viral suppression. These are the conclusions of the Switch to Raltegravir From Lopinavir in Highly Treatment-Experienced Patient (SWITCHMRK) 1 and 2 studies, reported in an article published online first and appearing in an upcoming edition of The Lancet. The 2 randomised, blinded SWITCHMRK trials compared substitution of raltegravir for lopinavir-ritonavir with continuation of lopinavir-ritonavir in HIV-positive patients with stable viral suppression on lopinavir-ritonavir-based combination therapy. For the study, Joseph J. Eron, MD, University of North Carolina School of Medicine, Chapel Hill, North Carolina, and colleagues randomised 707 patients in a 1:1 ratio to switch from lopinavir-ritonavir to raltegravir 400 mg twice daily (n = 353) or to remain on lopinavir-ritonavir given as two 200 mg/50 mg tablets twice daily (n = 354), while continuing background therapy consisting of at least 1 nucleoside or nucleotide reverse transcriptase inhibitors. Primary endpoints were the mean percentage change in blood fat concentrations from baseline to week 12; the proportion of patients with HIV RNA concentration <50 copies per mL at week 24 (with all treated patients who did not complete the study counted as failures) with a prespecified non-inferiority margin of -12% for each study; and the frequency of adverse events up to 24 weeks. The final results showed that 702 patients received at least 1 dose of study drug and were included in the efficacy and safety analyses (raltegravir, n = 350; lopinavir-ritonavir, n = 352). Percentage changes in lipid concentrations from baseline to week 12 were greater in the raltegravir group than in the lopinavir-ritonavir group in each study, yielding combined results for total cholesterol -12.6% vs 1.0%, non-HDL -15.0% vs 2.6%, and triglycerides -42.2% vs 6.2%. At week 24, 84% of patients in the raltegravir group had an HIV viral load of <50 copies per mL compared with 91% of patients in the lopinavir-ritonavir group (treatment difference -6.2%). Clinical and laboratory adverse events occurred at similar frequencies in the treatment groups. There were no serious drug-related adverse events or deaths. The only drug-related clinical adverse event of moderate to severe intensity reported in 1% or more of either treatment group was diarrhoea, which occurred in 10 patients in the lopinavir-ritonavir group (3%) and no patients in the raltegravir group. The studies were terminated at week 24 because of lower than expected virological efficacy in the raltegravir group compared with the lopinavir-ritonavir group. The authors discuss that the failure of raltegravir to be as effective at viral suppression in these patients as lopinavir-ritonavir (despite raltegravir reducing blood fats) underlines the complex considerations involved in providing the best possible care for individual patients. Since the studies were stopped early, a post-trial analysis was completed to understand why the differences in virological suppression had occurred. It was found that patients whose lopinavir-based regimen at screening was their first regimen or patients without previous virological failure had similar response rate at week 24 in both treatment groups in the two studies combined. Those patients who had previously failed other regimens may have had partial resistance to the nucleoside reverse transcriptase inhibitor in their regimen which could have contributed to the higher rate of virological failure when they switched to raltegravir. “In practice, clinicians need to gather all available background information, including past resistance tests and treatment outcomes, when contemplating the potential risks and benefits of modifying a suppressive antiretroviral regimen,” the authors wrote. “Efficacy, tolerability, and safety data from rigorous clinical trials that can be applied contextually to individual patients will help to inform these difficult decisions.” “Although switching to raltegravir was associated with greater reductions in serum lipid concentrations than was continuation of lopinavir-ritonavir, efficacy results did not establish non-inferiority of raltegravir to lopinavir-ritonavir.” SOURCE: The Lancet
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