Efficacy and safety of switching from boosted lopinavir to boosted atazanavir in patients with virological suppression receiving a LPV/r-containing HAART: the ATAZIP study.
OBJECTIVE
To evaluate the efficacy and safety of switching from boosted lopinavir (LPV/r) to boosted atazanavir (ATV/r) in virologically suppressed HIV-1-infected patients versus continuing LPV/r.


METHODS
Forty-eight weeks analysis of a randomized, open-label, noninferiority trial including patients with virological suppression (< or = 200 copies/mL for > or = 6 months) on LPV/r-containing triple highly active antiretroviral therapy. Patients (n = 248) were randomized 1:1 either to continue LPV/r twice a day (n = 127) or to switch to ATV/r every day (ATV/r; n = 121), with no change in nucleoside reverse transcriptase inhibitor backbone. Those known to have >4 protease inhibitor (PI)-associated mutations and/or who had failed >2 PI-containing regimens were excluded.


RESULTS
Baseline characteristics were balanced. 30% harboured > or = 1 PI-associated mutation (10% harboured > or = 1 major mutation). Treatment failure at 48 weeks (primary end point) occurred in 20% (25 of 127) of the LPV/r arm and in 17% (21 of 121) of the ATV/r arm (difference -2.3%; 95% confidence interval: -12.0 to 8.0; P = 0.0018). Virological failure occurred in 7% (9 of 127) of the LPV/r arm and in 5% (6 of 121) of the ATV/r arm (difference -2.1%; 95% confidence interval: -8.7% to 4.2%, P < 0.0001 for noninferiorating). CD4 changes from baseline were similar in each arm (approximately 40 cells/mm). Adverse event rate leading to study drug discontinuation was 5% in both arms. Median fasting triglycerides and total cholesterol decreased significantly in the ATV/r arm (-53 and -19 mg/dL, respectively versus -4 and -4 mg/dL in the LPV/r arm; P < 0.001 in both comparisons). Alanine aminotransferase/aspartate aminotransferase hepatic abnormalities were similar in the 2 arms.


CONCLUSIONS
Switching to ATV/r in virologically suppressed patients who were receiving a LPV/r-containing highly active antiretroviral therapy provided comparable (noninferior) efficacy and a safety profile with improved lipid parameters [ISRCTN24813210].
Mallolas
Josep
J
Hospital Clinic Universitari-IDIBAPS, University of Barcelona, Barcelona, Spain. mallolas@clinic.ub.es
Podzamczer
Daniel
D
Milinkovic
Ana
A
Domingo
Pere
P
Clotet
Bonaventura
B
Ribera
Esteve
E
Gutiérrez
Félix
F
Knobel
Hernando
H
Cosin
Jaime
J
Ferrer
Elena
E
Arranz
José Alberto
JA
Roca
Victor
V
Vidal
Francesc
F
Murillas
Javier
J
Pich
Judit
J
Pedrol
Enric
E
Llibre
Josep M
JM
Dalmau
David
D
García
Isabel
I
Aranda
Miquel
M
Cruceta
Ana
A
Martínez
Esteban
E
Blanco
José L
JL
Lazzari
Elisa de
Ed
Gatell
José M
JM
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects; D023241:Antiretroviral Therapy, Highly Active; D001219:Aspartate Aminotransferases / Q000097:blood; D000069446:Atazanavir Sulfate; D024882:Drug Resistance, Viral / Q000235:genetics; D004361:Drug Tolerance; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics; D006801:Humans; D008055:Lipids / Q000097:blood; D008099:Liver / Q000187:drug effects; D061466:Lopinavir; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009842:Oligopeptides / Q000008:administration & dosage* / Q000009:adverse effects; D011725:Pyridines / Q000008:administration & dosage* / Q000009:adverse effects; D011744:Pyrimidinones / Q000008:administration & dosage* / Q000009:adverse effects; D012449:Safety
D019380:Anti-HIV Agents; D008055:Lipids; D009842:Oligopeptides; D011725:Pyridines; D011744:Pyrimidinones; D061466:Lopinavir; D000069446:Atazanavir Sulfate; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase