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; J. A. Arnaiz; H. Beleta; D. Garcia; A. Pejenaute; N. Ramos; P. Arcaina; L. Giner; S. Moya; M. Pampliega; G. Barrera; N. Rozas; M. Saumoy; V. Asensi; A. González-Cordón; I. Pérez; E. Martínez; M. Masiá; S. Padilla; J. R. Ramos; C. Robledano; F. Gutiérrez; J. Puig; J. R. Arribas; J. M. Castro; J. Sanz; M. Cairó; P. Velli; D. Dalmau; A. Lamas; P. Martí-Belda; F. Dronda; J. R. Blanco; M. Gutierrez; M. G. Mateo; E. Losada; A. Prieto; A. Antela; A. Aguilar; M. Vargas; C. Viladés; F. Vidal; M. Crespo

doi:10.1093/cid/ciu898

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, J. A. ArnaizH. Beleta, D. Garcia, A. Pejenaute, N. Ramos, P. Arcaina, L. Giner, S. Moya, M. Pampliega, G. Barrera, N. Rozas, M. Saumoy, V. Asensi, A. González-Cordón, I. Pérez, E. Martínez, M. Masiá, S. Padilla, J. R. Ramos, C. Robledano, F. Gutiérrez, J. Puig, J. R. Arribas, J. M. Castro, J. Sanz, M. Cairó, P. Velli, D. Dalmau, A. Lamas, P. Martí-Belda, F. Dronda, J. R. Blanco, M. Gutierrez, M. G. Mateo, E. Losada, A. Prieto, A. Antela, A. Aguilar, M. Vargas, C. Viladés, F. Vidal, M. Crespo

Research output: Contribution to journal › Article › Research › peer-review

22 Citations (Scopus)

Abstract

© The Author 2014. Background. It is unclear whether metabolic or body composition effects differ between protease inhibitorbased 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 cm2; 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.

Original language	English
Pages (from-to)	811-820
Journal	Clinical Infectious Diseases
Volume	60
Issue number	5
DOIs	https://doi.org/10.1093/cid/ciu898
Publication status	Published - 1 Jan 2015

Keywords

Antiretroviral therapy
Body composition
HIV protease inhibitors
Plasma lipids

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Martinez, E., Gonzalez-Cordon, A., Ferrer, E., Domingo, P., Negredo, E., Gutierrez, F., Portilla, J., Curran, A., Podzamczer, D., Ribera, E., Murillas, J., Bernardino, J. I., Santos, I., Carton, J. A., Peraire, J., Pich, J., Deulofeu, R., Perez, I., Gatell, J. M., ... Crespo, M. (2015). Differential body composition effects of protease inhibitors recommended for initial treatment of HIV infection: A randomized clinical trial. Clinical Infectious Diseases, 60(5), 811-820. https://doi.org/10.1093/cid/ciu898

Martinez, Esteban ; Gonzalez-Cordon, Ana ; Ferrer, Elena ; Domingo, Pere ; Negredo, Eugenia ; Gutierrez, Felix ; Portilla, Joaquin ; Curran, Adrià ; Podzamczer, Daniel ; Ribera, Esteban ; Murillas, Javier ; Bernardino, Jose I. ; Santos, Ignacio ; Carton, Jose A. ; Peraire, Joaquim ; Pich, Judit ; Deulofeu, Ramon ; Perez, Ignacio ; Gatell, Jose M. ; Arnaiz, J. A. ; Beleta, H. ; Garcia, D. ; Pejenaute, A. ; Ramos, N. ; Arcaina, P. ; Giner, L. ; Moya, S. ; Pampliega, M. ; Barrera, G. ; Rozas, N. ; Saumoy, M. ; Asensi, V. ; González-Cordón, A. ; Pérez, I. ; Martínez, E. ; Masiá, M. ; Padilla, S. ; Ramos, J. R. ; Robledano, C. ; Gutiérrez, F. ; Puig, J. ; Arribas, J. R. ; Castro, J. M. ; Sanz, J. ; Cairó, M. ; Velli, P. ; Dalmau, D. ; Lamas, A. ; Martí-Belda, P. ; Dronda, F. ; Blanco, J. R. ; Gutierrez, M. ; Mateo, M. G. ; Losada, E. ; Prieto, A. ; Antela, A. ; Aguilar, A. ; Vargas, M. ; Viladés, C. ; Vidal, F. ; Crespo, M. / Differential body composition effects of protease inhibitors recommended for initial treatment of HIV infection: A randomized clinical trial. In: Clinical Infectious Diseases. 2015 ; Vol. 60, No. 5. pp. 811-820.

@article{97bd6570a33c4a12b84bc3e940a26113,

title = "Differential body composition effects of protease inhibitors recommended for initial treatment of HIV infection: A randomized clinical trial",

abstract = "{\textcopyright} The Author 2014. Background. It is unclear whether metabolic or body composition effects differ between protease inhibitorbased 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 cm2; 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 = "Antiretroviral therapy, Body composition, HIV protease inhibitors, Plasma lipids",

author = "Esteban Martinez and Ana Gonzalez-Cordon and Elena Ferrer and Pere Domingo and Eugenia Negredo and Felix Gutierrez and Joaquin Portilla and Adri{\`a} Curran and Daniel Podzamczer and Esteban Ribera and Javier Murillas and Bernardino, {Jose I.} and Ignacio Santos and Carton, {Jose A.} and Joaquim Peraire and Judit Pich and Ramon Deulofeu and Ignacio Perez and Gatell, {Jose M.} and Arnaiz, {J. A.} and H. Beleta and D. Garcia and A. Pejenaute and N. Ramos and P. Arcaina and L. Giner and S. Moya and M. Pampliega and G. Barrera and N. Rozas and M. Saumoy and V. Asensi and A. Gonz{\'a}lez-Cord{\'o}n and I. P{\'e}rez and E. Mart{\'i}nez and M. Masi{\'a} and S. Padilla and Ramos, {J. R.} and C. Robledano and F. Guti{\'e}rrez and J. Puig and Arribas, {J. R.} and Castro, {J. M.} and J. Sanz and M. Cair{\'o} and P. Velli and D. Dalmau and A. Lamas and P. Mart{\'i}-Belda and F. Dronda and Blanco, {J. R.} and M. Gutierrez and Mateo, {M. G.} and E. Losada and A. Prieto and A. Antela and A. Aguilar and M. Vargas and C. Vilad{\'e}s and F. Vidal and M. Crespo",

year = "2015",

month = jan,

day = "1",

doi = "10.1093/cid/ciu898",

language = "English",

volume = "60",

pages = "811--820",

journal = "Clinical Infectious Diseases",

issn = "1058-4838",

number = "5",

}

Martinez, E, Gonzalez-Cordon, A, Ferrer, E, Domingo, P, Negredo, E, Gutierrez, F, Portilla, J, Curran, A, Podzamczer, D, Ribera, E, Murillas, J, Bernardino, JI, Santos, I, Carton, JA, Peraire, J, Pich, J, Deulofeu, R, Perez, I, Gatell, JM, Arnaiz, JA, Beleta, H, Garcia, D, Pejenaute, A, Ramos, N, Arcaina, P, Giner, L, Moya, S, Pampliega, M, Barrera, G, Rozas, N, Saumoy, M, Asensi, V, González-Cordón, A, Pérez, I, Martínez, E, Masiá, M, Padilla, S, Ramos, JR, Robledano, C, Gutiérrez, F, Puig, J, Arribas, JR, Castro, JM, Sanz, J, Cairó, M, Velli, P, Dalmau, D, Lamas, A, Martí-Belda, P, Dronda, F, Blanco, JR, Gutierrez, M, Mateo, MG, Losada, E, Prieto, A, Antela, A, Aguilar, A, Vargas, M, Viladés, C, Vidal, F & Crespo, M 2015, 'Differential body composition effects of protease inhibitors recommended for initial treatment of HIV infection: A randomized clinical trial', Clinical Infectious Diseases, vol. 60, no. 5, pp. 811-820. https://doi.org/10.1093/cid/ciu898

Differential body composition effects of protease inhibitors recommended for initial treatment of HIV infection: A randomized clinical trial. / Martinez, Esteban; Gonzalez-Cordon, Ana; Ferrer, Elena; Domingo, Pere; Negredo, Eugenia; Gutierrez, Felix; Portilla, Joaquin; Curran, Adrià; Podzamczer, Daniel; Ribera, Esteban; Murillas, Javier; Bernardino, Jose I.; Santos, Ignacio; Carton, Jose A.; Peraire, Joaquim; Pich, Judit; Deulofeu, Ramon; Perez, Ignacio; Gatell, Jose M.; Arnaiz, J. A.; Beleta, H.; Garcia, D.; Pejenaute, A.; Ramos, N.; Arcaina, P.; Giner, L.; Moya, S.; Pampliega, M.; Barrera, G.; Rozas, N.; Saumoy, M.; Asensi, V.; González-Cordón, A.; Pérez, I.; Martínez, E.; Masiá, M.; Padilla, S.; Ramos, J. R.; Robledano, C.; Gutiérrez, F.; Puig, J.; Arribas, J. R.; Castro, J. M.; Sanz, J.; Cairó, M.; Velli, P.; Dalmau, D.; Lamas, A.; Martí-Belda, P.; Dronda, F.; Blanco, J. R.; Gutierrez, M.; Mateo, M. G.; Losada, E.; Prieto, A.; Antela, A.; Aguilar, A.; Vargas, M.; Viladés, C.; Vidal, F.; Crespo, M.

In: Clinical Infectious Diseases, Vol. 60, No. 5, 01.01.2015, p. 811-820.

Research output: Contribution to journal › Article › Research › peer-review

TY - JOUR

T1 - Differential body composition effects of protease inhibitors recommended for initial treatment of HIV infection: A randomized clinical trial

AU - Martinez, Esteban

AU - Gonzalez-Cordon, Ana

AU - Ferrer, Elena

AU - Domingo, Pere

AU - Negredo, Eugenia

AU - Gutierrez, Felix

AU - Portilla, Joaquin

AU - Curran, Adrià

AU - Podzamczer, Daniel

AU - Ribera, Esteban

AU - Murillas, Javier

AU - Bernardino, Jose I.

AU - Santos, Ignacio

AU - Carton, Jose A.

AU - Peraire, Joaquim

AU - Pich, Judit

AU - Deulofeu, Ramon

AU - Perez, Ignacio

AU - Gatell, Jose M.

AU - Arnaiz, J. A.

AU - Beleta, H.

AU - Garcia, D.

AU - Pejenaute, A.

AU - Ramos, N.

AU - Arcaina, P.

AU - Giner, L.

AU - Moya, S.

AU - Pampliega, M.

AU - Barrera, G.

AU - Rozas, N.

AU - Saumoy, M.

AU - Asensi, V.

AU - González-Cordón, A.

AU - Pérez, I.

AU - Martínez, E.

AU - Masiá, M.

AU - Padilla, S.

AU - Ramos, J. R.

AU - Robledano, C.

AU - Gutiérrez, F.

AU - Puig, J.

AU - Arribas, J. R.

AU - Castro, J. M.

AU - Sanz, J.

AU - Cairó, M.

AU - Velli, P.

AU - Dalmau, D.

AU - Lamas, A.

AU - Martí-Belda, P.

AU - Dronda, F.

AU - Blanco, J. R.

AU - Gutierrez, M.

AU - Mateo, M. G.

AU - Losada, E.

AU - Prieto, A.

AU - Antela, A.

AU - Aguilar, A.

AU - Vargas, M.

AU - Viladés, C.

AU - Vidal, F.

AU - Crespo, M.

PY - 2015/1/1

Y1 - 2015/1/1

N2 - © The Author 2014. Background. It is unclear whether metabolic or body composition effects differ between protease inhibitorbased 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 cm2; 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.

AB - © The Author 2014. Background. It is unclear whether metabolic or body composition effects differ between protease inhibitorbased 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 cm2; 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.

KW - Antiretroviral therapy

KW - Body composition

KW - HIV protease inhibitors

KW - Plasma lipids

U2 - 10.1093/cid/ciu898

DO - 10.1093/cid/ciu898

M3 - Article

VL - 60

SP - 811

EP - 820

JO - Clinical Infectious Diseases

JF - Clinical Infectious Diseases

SN - 1058-4838

IS - 5

ER -