Early lipid changes with atazanavir/ritonavir or darunavir/ritonavir
Por:
Martinez, E, Gonzalez-Cordon, A, Ferrer, E, Domingo, P, Negredo, E, Gutierrez, F, Portilla, J, Curran, A, Podzamczer, D, Murillas, J, Bernardino, JI, Santos, I, Carton, JA, Peraire, J, Pich, J, Perez, I and Gatell, JM
Publicada:
1 jul 2014
Resumen:
Objectives Ritonavir-boosted atazanavir and darunavir are protease inhibitors that are recommended for initial treatment of HIV infection because each has shown better lipid effects and overall tolerability than ritonavir-boosted lopinavir. The extent to which lipid effects and overall tolerability differ between treatments with atazanavir and darunavir and whether atazanavir-induced hyperbilirubinaemia may result in more favourable metabolic effects are issues that remain to be resolved. Methods A 96-week randomized clinical trial was carried out. The primary endpoint was change in total cholesterol at 24 weeks. Secondary endpoints were changes in lipids other than total cholesterol, insulin sensitivity, total bilirubin, estimated glomerular filtration rate, and CD4 and CD8 cell counts, and the proportion of patients with plasma HIV RNA <50 HIV-1 RNA copies/mL and study drug discontinuation because of adverse effects at 24 weeks. Analyses were intent-to-treat. Results One hundred and seventy-eight patients received once-daily treatment with either atazanavir/ritonavir (n=90) or darunavir/ritonavir (n=88) plus tenofovir/emtricitabine. At 24 weeks, mean total cholesterol had increased by 7.26 and 11.47mg/dL in the atazanavir/ritonavir and darunavir/ritonavir arms, respectively [estimated difference -4.21mg/dL; 95% confidence interval (CI) -12.11 to +3.69mg/dL; P=0.75]. However, the ratio of total to high-density lipoprotein (HDL) cholesterol tended to show a greater decrease with atazanavir/ritonavir compared with darunavir/ritonavir (estimated difference -1.02; 95% CI -2.35 to +0.13; P=0.07). Total bilirubin significantly increased with atazanavir/ritonavir (estimated difference +1.87mg/dL; 95% CI +1.58 to +2.16mg/dL; P<0.01), but bilirubin changes were not associated with lipid changes. Secondary endpoints other than total bilirubin were not significantly different between arms. Conclusions Atazanavir/ritonavir and darunavir/ritonavir plus tenofovir/emtricitabine did not show significant differences in total cholesterol change or overall tolerability at 24 weeks. However, there was a trend towards a lower total to HDL cholesterol ratio with atazanavir/ritonavir and this effect was unrelated to bilirubin.
Filiaciones:
Martinez, E:
Univ Barcelona, Hosp Clin, IDIBAPS, E-08036 Barcelona, Spain
Gonzalez-Cordon, A:
Univ Barcelona, Hosp Clin, IDIBAPS, E-08036 Barcelona, Spain
Ferrer, E:
Univ Barcelona, Hosp Univ Bellvitge, Lhospitalet De Llobregat, Spain
Domingo, P:
Univ Autonoma Barcelona, Hosp St Pau, E-08193 Barcelona, Spain
:
Univ Autonoma Barcelona, Lluita SIDA Fdn, Hosp Germans Trias & Pujol, Badalona, Spain
Gutierrez, F:
Univ Miguel Hernandez, Hosp Univ Elche, Elche, Spain
Portilla, J:
Univ Alicante, Hosp Univ Alicante, E-03080 Alicante, Spain
Curran, A:
Univ Autonoma Barcelona, Hosp Univ Vall dHebron, E-08193 Barcelona, Spain
Podzamczer, D:
Univ Barcelona, Hosp Univ Bellvitge, Lhospitalet De Llobregat, Spain
Murillas, J:
Hosp Son Espases, Palma De Mallorca, Spain
Bernardino, JI:
Univ Autonoma Madrid, Hosp Univ La Paz, Madrid, Spain
Santos, I:
Univ Autonoma Madrid, Hosp Univ La Princesa, Madrid, Spain
Carton, JA:
Univ Oviedo, Hosp Univ Cent Asturias, Oviedo, Spain
Peraire, J:
Univ Rovira & Virgili, Hosp Univ Joan 23, E-43007 Tarragona, Spain
Pich, J:
Univ Barcelona, Hosp Clin, IDIBAPS, E-08036 Barcelona, Spain
Perez, I:
Univ Barcelona, Hosp Clin, IDIBAPS, E-08036 Barcelona, Spain
Gatell, JM:
Univ Barcelona, Hosp Clin, IDIBAPS, E-08036 Barcelona, Spain
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