Differential body composition effects of protease inhibitors recommended for initial treatment of HIV infection: a randomized clinical trial
Esteban Martinez, Ana Gonzalez-Cordon, Elena Ferrer, Pere Domingo, Eugenia Negredo, Felix Gutierrez, Joaquin Portilla, Adrià Curran, Daniel Podzamczer, Esteban Ribera, Javier Murillas, Jose I Bernardino, Ignacio Santos, Jose A Carton, Joaquim Peraire, Judit Pich, Ramon Deulofeu, Ignacio Perez, Jose M Gatell, ATADAR Study Group, Esteban Martínez, José M Gatell, Juan A Arnaiz, Helena Beleta, David Garcia, Judit Pich, Andrea Pejenaute, Nuria Ramos, Ignacio Pérez, P Arcaina, L Giner, S Moya, M Pampliega, J Portilla, G Barrera, D Podzamczer, N Rozas, M Saumoy, E Ferrer, V Asensi, J A Cartón, J M Gatell, A González-Cordón, I Pérez, E Martínez, M Masiá, S Padilla, J R Ramos, C Robledano, F Gutiérrez, J Puig, E Negredo, J R Arribas, J M Castro, J I Bernardino, J Sanz, I Santos, M Cairó, P Velli, D Dalmau, A Lamas, P Martí-Belda, F Dronda, J R Blanco, M Gutierrez, M G Mateo, P Domingo, E Losada, A Prieto, A Antela, J Murillas, A Aguilar, J Peraire, M Vargas, C Viladés, F Vidal, M Crespo, A Curran, E Ribera, J A Arnaiz, H Beleta, D Garcia, A Pejenaute, N Ramos, J Pich, Esteban Martinez, Ana Gonzalez-Cordon, Elena Ferrer, Pere Domingo, Eugenia Negredo, Felix Gutierrez, Joaquin Portilla, Adrià Curran, Daniel Podzamczer, Esteban Ribera, Javier Murillas, Jose I Bernardino, Ignacio Santos, Jose A Carton, Joaquim Peraire, Judit Pich, Ramon Deulofeu, Ignacio Perez, Jose M Gatell, ATADAR Study Group, Esteban Martínez, José M Gatell, Juan A Arnaiz, Helena Beleta, David Garcia, Judit Pich, Andrea Pejenaute, Nuria Ramos, Ignacio Pérez, P Arcaina, L Giner, S Moya, M Pampliega, J Portilla, G Barrera, D Podzamczer, N Rozas, M Saumoy, E Ferrer, V Asensi, J A Cartón, J M Gatell, A González-Cordón, I Pérez, E Martínez, M Masiá, S Padilla, J R Ramos, C Robledano, F Gutiérrez, J Puig, E Negredo, J R Arribas, J M Castro, J I Bernardino, J Sanz, I Santos, M Cairó, P Velli, D Dalmau, A Lamas, P Martí-Belda, F Dronda, J R Blanco, M Gutierrez, M G Mateo, P Domingo, E Losada, A Prieto, A Antela, J Murillas, A Aguilar, J Peraire, M Vargas, C Viladés, F Vidal, M Crespo, A Curran, E Ribera, J A Arnaiz, H Beleta, D Garcia, A Pejenaute, N Ramos, J Pich
Abstract
Background: It is unclear whether metabolic or body composition effects differ between protease inhibitor-based regimens recommended for initial treatment of human immunodeficiency virus (HIV) infection.
Methods: ATADAR is a phase 4, open-label, multicenter, randomized clinical trial. Stable antiretroviral-naive HIV-infected adults were randomly assigned to atazanavir/ritonavir 300/100 mg or darunavir/ritonavir 800/100 mg in combination with tenofovir/emtricitabine daily. Predefined endpoints were treatment or virological failure, drug discontinuation due to adverse effects, and laboratory and body composition changes at 96 weeks.
Results: At 96 weeks, 56 (62%) atazanavir/ritonavir and 62 (71%) darunavir/ritonavir patients remained free of treatment failure (estimated difference 8.2%; 95% confidence interval [CI], -.6 to 21.6) and 71 (79%) atazanavir/ritonavir and 75 (85%) darunavir/ritonavir patients remained free of virological failure (estimated difference 6.3%; 95% CI, -.5 to 17.6). Seven patients discontinued atazanavir/ritonavir and 5 discontinued darunavir/ritonavir due to adverse effects. Total and high-density lipoprotein cholesterol similarly increased in both arms, but there was a greater increase in triglycerides in the atazanavir/ritonavir arm. At 96 weeks, body fat (estimated difference 2862.2 gr; 95% CI, 726.7 to 4997.7; P = .0090), limb fat (estimated difference 1403.3 gr; 95% CI, 388.4 to 2418.2; P = .0071), and subcutaneous abdominal adipose tissue (estimated difference 28.4 cm(2); 95% CI, 1.9 to 55.0; P = .0362) increased more in the atazanavir/ritonavir arm than in darunavir/ritonavir arm. Body fat changes in the atazanavir/ritonavir arm were associated with higher insulin resistance.
Conclusions: We found no major differences between atazanavir/ritonavir and darunavir/ritonavir in efficacy, clinically relevant side effects, or plasma cholesterol fractions. However, atazanavir/ritonavir led to higher triglycerides and more total and subcutaneous fat than darunavir/ritonavir. Also, fat gains with atazanavir/ritonavir were associated with insulin resistance. Clinical Trials Registration. NCT01274780.
Keywords: HIV protease inhibitors; antiretroviral therapy; body composition; plasma lipids.
© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
Source: PubMed