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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Once-daily atazanavir/ritonavir versus twice-daily lopinavir/ritonavir, each in combination with tenofovir and emtricitabine, for management of antiretroviral-naive HIV-1-infected patients: 48 week efficacy and safety results of the CASTLE study
The Lancet, Volume 372, No. 9639, Year 2008
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Description
Background: 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. We compared these two combinations directly in treatment-naive patients. Methods: In this open-label, international non-inferiority study, 883 antiretroviral-naive, HIV-1-infected patients were randomly assigned to receive 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 once daily. Randomisation was done with a computer-generated centralised randomisation schedule and was stratified by baseline levels of HIV RNA (viral load) and geographic region. The primary endpoint was the proportion of patients with viral load less than 50 copies per mL at week 48. The main efficacy analysis was done by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00272779. Findings: At week 48, 343 (78%) of 440 patients receiving atazanavir/ritonavir and 338 (76%) of 443 patients receiving lopinavir/ritonavir had achieved a viral load of less than 50 copies per mL (difference 1·7%, 95% CI -3·8 to 7·1). Mean increases from baseline in CD4 cell count were similar (203 cells per μL in the atazanavir/ritonavir group vs 219 cells per μL in the lopinavir/ritonavir group). 25 (6%) patients in the atazanavir/ritonavir group and 26 (6%) in the lopinavir/ritonavir group were virological failures by week 48. Only two patients, both in the atazanavir/ritonavir group, had non-polymorphic protease inhibitor resistance mutations emerge on treatment, which conferred phenotypic resistance to atazanavir in one patient. Serious adverse events were noted in 51 (12%) of 441 patients in the atazanavir/ritonavir group and in 42 (10%) of 437 patients in the lopinavir/ritonavir group. Fewer patients in the atazanavir/ritonavir group than in the lopinavir/ritonavir group experienced grade 2-4 treatment-related diarrhoea (10 [2%] vs 50 [11%]) and nausea (17 [4%] vs 33 [8%]). Grade 2-4 jaundice was seen in 16 (4%) of 441 patients in the atazanavir/ritonavir group versus none of 437 patients in the lopinavir/ritonavir group; grade 3-4 increases in total bilirubin were seen in 146 (34%) of 435 patients on atazanavir/ritonavir and in one (<1%) of 431 patients on lopinavir/ritonavir. Interpretation: 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. Funding: Bristol-Myers Squibb. © 2008 Elsevier Ltd. All rights reserved.
Authors & Co-Authors
Molina, Jean Michel
France, Paris
Hôpital Saint-louis
France, Paris
Université Paris Cité
Andrade-Villanueva, Jaime
Mexico, Guadalajara
Hospital Civil de Guadalajara
Echevarría, Juan
Peru, Lima
Hospital Nacional Cayetano Heredia
Chetchotisakd, Ploenchan
Thailand, Khon Kaen
Khon Kaen University
Corral, Jorge A.
Argentina, Buenos Aires
Hospital Interzonal de Agudos Oscar Alende
David, Neal
South Africa, Brooklyn
Brooklyn
Moyle, Graeme J.
United Kingdom, London
Chelsea and Westminster Hospital
Mancini, Marco
United States, New York
Bristol-myers Squibb
Percival, Lisa
United States, New York
Bristol-myers Squibb
Yang, Rong
United States, New York
Bristol-myers Squibb
Thiry, Alexandra
United States, New York
Bristol-myers Squibb
McGrath, Donnie
United States, New York
Bristol-myers Squibb
Statistics
Citations: 514
Authors: 12
Affiliations: 9
Identifiers
Doi:
10.1016/S0140-6736(08)61081-8
ISSN:
01406736
Research Areas
Health System And Policy
Infectious Diseases