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| |  Ritonavir-Sparing and Nucleoside Dual HIV Regimen Lowers Virus Levels, but Safety and Resistance Derail Study: Presented at AIDS 2010 By Ed Susman VIENNA -- July 27, 2010 -- An experimental treatment combining the integrase inhibitor raltegravir and the protease inhibitor atazanavir successfully reduced HIV to undetectable levels, but the emergence of resistance and other side effects has resulted in the program being abandoned by its sponsors, researchers reported here at the 18th International AIDS Conference. The 2-drug combination -- the main subject of the so-called SPARTAN trial -- appeared to lower virus at least as well as the standard boosted atazanavir/ritonavir-based regimen, which also employed nucleoside reverse transcriptase inhibitors, said author Michael J Kozal, MD, Yale HIV Clinical Trials, Yale University, New Haven, Connecticut. Unfortunately, the experimental coupling had several problems, Dr. Kozal added. The 2-drug combination required twice-daily dosing compared with single-daily dosing for the standard therapy. Additionally, resistance to raltegravir was seen in 6% of patients in the experimental arm. Finally, evidence of bilirubin -- often seen with atazanavir -- appeared to occur more often in the 2-drug combination. Dr. Kozal noted that all of those concerns played a role in the decision by Merck and Bristol-Myers Squibb to halt the program. He reported the results from the study in his oral late-breaker oral presentation here on July 22. The research team enrolled 94 patients naïve to antiretroviral treatment to receive either a regimen of atazanavir and raltegravir twice a day and compared these 64 patients with a reference cohort of 31 patients infected with HIV who were treated with a once-daily regimen of atazanavir boosted with ritonavir plus the nucleoside reverse transcriptase inhibitor combination tenofovir/emtricitabine. At 24 weeks, 74.6% of the patients on simplified regimen achieved suppression of the virus to undetectable levels based on the 50-copy/mL assay, while 63.3% of the patients on the once-daily regimen achieved that endpoint. The 2 groups were used for comparison purposes, but statistical significance was not calculated. Dr. Kozal reported that 4 of the 63 patients on the raltegravir combination developed resistance to the integrase inhibitor. About 60.3% of patients in the atazanavir/raltegravir group experienced grade 3 or 4 bilirubin abnormalities, while 46.7% of the 3-drug combination patients experienced grade 3 to 4 bilirubin abnormalities. "There were no new or unexpected safety signals for raltegravir 400 mg twice a day dosing," Dr. Kozal noted. [Presentation title: The SPARTAN Study: A Pilot Study to Assess the Safety and Efficacy of an Investigational NRTI- and RTV-Sparing Regimen of Atazanavir (ATV) Experimental Dose of 300mg BID Plus Raltegravir (RAL) 400mg BID (ATV+RAL) in Treatment-Naïve HIV-Infected Subjects. Abstract THLBB204]
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