Differential body composition effects of protease inhibitors recommended for initial treatment of HIV infection: a randomized clinical trial.
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.
Hospital Clínic-IDIBAPS, Universitat de Barcelona.
Esteban
E
Martinez
Hospital Clínic-IDIBAPS, Universitat de Barcelona.
Ana
A
Gonzalez-Cordon
Hospital Universitari de Bellvitge, Universitat de Barcelona, L'Hospitalet de Llobregat.
Elena
E
Ferrer
Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona.
Pere
P
Domingo
Lluita Contra la SIDA Foundation, Hospital Germans Trías i Pujol, Universitat Autònoma de Barcelona, Badalona.
Eugenia
E
Negredo
Hospital Universitario de Elche, Universidad Miguel Hernández.
Felix
F
Gutierrez
Hospital Universitario de Alicante, Universidad de Alicante.
Joaquin
J
Portilla
Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona.
Adrià
A
Curran
Hospital Universitari de Bellvitge, Universitat de Barcelona, L'Hospitalet de Llobregat.
Daniel
D
Podzamczer
Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona.
Esteban
E
Ribera
Hospital Son Espases, Palma de Mallorca.
Javier
J
Murillas
Hospital Universitario La Paz, Universidad Autónoma de Madrid.
Jose I
JI
Bernardino
Hospital Universitario de La Princesa, Universidad Autónoma de Madrid.
Ignacio
I
Santos
Hospital Universitario Central de Asturias, Universidad de Oviedo.
Jose A
JA
Carton
Hospital Universitari Joan XXIII, Universitat Rovira i Virgili, Tarragona, Spain.
Joaquim
J
Peraire
Hospital Clínic-IDIBAPS, Universitat de Barcelona.
Judit
J
Pich
Hospital Clínic-IDIBAPS, Universitat de Barcelona.
Ramon
R
Deulofeu
Hospital Clínic-IDIBAPS, Universitat de Barcelona.
Ignacio
I
Perez
Hospital Clínic-IDIBAPS, Universitat de Barcelona.
Jose M
JM
Gatell
D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D001823:Body Composition / Q000187:drug effects*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use*; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D019562:Viral Load
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors
HIV protease inhibitors; antiretroviral therapy; body composition; plasma lipids