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【medical-news】《Lancet》阿扎那韦/利托那韦每日一
"Atazanavir/ritonavir is as effective as lopinavir/ritonavir, with a more favourable lipid profile and less gastrointestinal toxicity, in treatment-experienced HIV-1-infected patients," write Jean-Michel Molina, MD, from Saint-Louis Hospital, AP-HP, Paris, and University of Paris-Diderot, in France, and colleagues from the CASTLE Study Team. "We compared these two combinations directly in treatment-naive patients."
The study sample consisted of 883 antiretroviral-naive, HIV-1–infected patients who were randomly assigned to receive treatment with atazanavir/ritonavir 300/100 mg once daily (n = 440) or lopinavir/ritonavir 400/100 mg twice daily (n = 443), in combination with fixed-dose tenofovir/emtricitabine 300/200 mg given once daily.
A computer-generated centralized randomization schedule stratified participants by baseline levels of HIV RNA (viral load) and geographic region. Efficacy analysis was by intent-to-treat, with the main outcome measure being the proportion of patients with viral load less than 50 copies per mL at week 48.
Viral load of less than 50 copies per mL at week 48 was achieved by 343 (78%) of 440 patients receiving atazanavir/ritonavir and by 338 (76%) of 443 patients receiving lopinavir/ritonavir (difference, 1.7%; 95% confidence interval [CI], –3.8 to 7.1). Both groups had similar mean increases from baseline in CD4 cell count (203 cells per μL in the atazanavir/ritonavir group vs 219 cells per μL in the lopinavir/ritonavir group).
By week 48, virologic failures occurred in 25 (6%) patients in the atazanavir/ritonavir group and 26 (6%) in the lopinavir/ritonavir group. There were only 2 patients, both in the atazanavir/ritonavir group, in whom nonpolymorphic protease-inhibitor–resistance mutations emerged with treatment. In 1 of these 2 patients, these mutations conferred phenotypic resistance to atazanavir.
Serious adverse events occurred in 51 (12%) of 441 patients in the atazanavir/ritonavir group and in 42 (10%) of 437 patients in the lopinavir/ritonavir group. Compared with patients in the lopinavir/ritonavir group, fewer patients in the atazanavir/ritonavir group had grade 2 to 4 treatment-related diarrhea (10 [2%] vs 50 [11%]) and nausea (17 [4%] vs 33 [8%]).
Grade 2 to 4 jaundice occurred in 16 (4%) of 441 patients in the atazanavir/ritonavir group but in none of 437 patients in the lopinavir/ritonavir group. There were grade 3 to 4 increases in total bilirubin levels in 146 (34%) of 435 patients in the atazanavir/ritonavir group and in 1 (< 1%) of 431 patients in the lopinavir/ritonavir group.
Limitations of this study include open-label design and use of 3 capsules twice daily of lopinavir/ritonavir during the 48-week assessment period, rather than the newer tablet formulation of 2 tablets twice daily.
"In treatment-naive patients, atazanavir/ritonavir once-daily demonstrated similar antiviral efficacy to lopinavir/ritonavir twice-daily, with less gastrointestinal toxicity but with a higher rate of hyperbilirubinaemia," the study authors write. "The results of this study support the use of once-daily atazanavir/ritonavir as a recommended first-line treatment option, with a number of patient benefits over the currently recommended ritonavir-boosted twice-daily lopinavir for the treatment of HIV-infected antiretroviral-naive patients."
Bristol-Myers Squibb supported this study. Five of the study authors are employees with Bristol-Myers Squibb. Four of the study authors have disclosed various financial relationships with Bristol-Myers Squibb, GlaxoSmithKline, Abbott, Gilead, Tibotec, Pfizer, Merck Sharpe & Dohme, Abbott, Schering-Plough, Anormed Inc, Ardea, Gilead, Merck Inc, Theratechnologies, Tobira Pharmaceuticals, and/or Tibotec/Johnson & Johnson. The remaining 3 study authors have disclosed no relevant financial relationships.
Lancet. Published online August 2, 2008. [标签:content1][标签:content2]
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作者:admin@医学,生命科学 2011-04-07 18:32
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