Efficacy and safety of switching from boosted Lopinavir (LPV/r) to boosted Atazanavir (ATV/r) in patients with virologic suppression receiving a LPV/r containing HAART: The ATAZIP study
Reported by Jules Levin
IAS Conference 22-25 July, 2007, Sydney, Australia
Mallolas J.1, Podzamczer D.2, Domingo P.3, Clotet B.4, Ribera E.5, Gutierrez F.6, Knobel H.7, Cosin J.8, Ferrer E.2, Arranz J.A.9, Roca V. á10, Vidal F.13, Peľaranda M.14, Pedrol E.15, Llibre J.M.16, Dalmau D.17, Garcia I.18, Aranda M.19, Pich J.11, de Lazzari E.12, Gatell J.M.1, for the ATAZIP study group
Switching to ATV/r in virologically suppressed patients who were receiving a LPV/r containing HAART provided comparable efficacy (meets non-inferiority criteria) and safety profile.
It was associated with improved lipid parameters (triglycerides and total cholesterol).
See the data below: Viral failure (>200 c/ml): 5% ATV/r, 6% LPV/r. See lab abnormalities, lipids, AEs below.
ATV is a potent, well-tolerated, once-daily (QD) protease inhibitor (PI) extensively studied in treatment-naive and -experienced patients
The SWAN study (BMS 097)1 demonstrated that switching from PI ▒ RTV-containing regimens to an unboosted ATV-containing regimen maintained virologic suppression with improvement in plasma lipids through 48 weeks in patients without previous failures to PI containing regimens
However, there are limited data available on the utility of switching virologically suppressed patients from LPV/r-based regimens to a different boosted PI such as ATV/r including those with previous failures to PI containing regimens or PI associated mutations
1Gatell et al. Clin Infect Dis 2007
To assess the safety and efficacy of ATV/r based HAART in virologically suppressed patients receiving a LPV/r containing regimen including patients with previous failures (< 3) to PI regimens or history of having PI associated mutations (< 5) prior to starting the LPV/r-based regimen.
265 patients stable on Kaletra based regimen for >6 months and VL <200 and <3 previous viral failures while on PI based HAART and <5 PI mutations were randomized to switch to ATV/r qd or continue Kaletra bid. The primary analysis was at week 48, final analysis at week 96.
The proportion of patients with treatment failure for any reason through Week 48
--Includes virologic rebound (> 200 cp/mL), discontinuation of study therapy or lost to follow-up, progression to a new CDC event or death.
--Non-inferiority study. Upper limit of 95% CI of estimated difference < 12.5%.
The proportion of patients with virologic rebound at or prior to Week 48
--Confirmed on-study HIV RNA ≥ 200 copies/mL or last on-study HIV RNA ≥ 200 copies/mL followed by discontinuation
Time to treatment failure and to virologic failure
Evolution of fasting plasma lipids
--Risk factors for virological failure
--Focusing on those with < 50 copies at baseline
--Focusing on patients with previous PI failures or history of PI resistance mutations
Patient Disposition at month 12
Discontinuation rates 13% for those switched to ATV/r, 14% for those continuing on Kaletra: 1 for viral failure on atv/r and 1 on lpv/r; for adverse events, 6 on each arm; for ďpatient decision, 2 on lpv/r, 0 atv/r. For patients continuing assigned therapy: discts. 5 for viral failure on ATV/r and 7 on LPV/r.
Treatment Failure and Virologic Failure (≥ 200 c/mL) through month 12
20% treatment failure for LPV/r, 17% for ATV/r (p=0.7). Viral failure (>200 c.ml): 6% lpv/r (8/127), 5% ATV/r (6/121) (p=0.08).
Median changes from baseline in CD4 cell count were similar beteween groups: +26 cells/mm3 (ATV/r) and +51 cells/mm3 (LPV/r) at month 12 (p=0.2)
Adverse Events through month 12
There were total of 6 in each group; GI-related: 1 in ATV/r, 2 LPV/r; CNS, 1 in ATV/r, 1 in LPV/r; liver: 1 in ATV/r, 1 in LPV/r; metabolic-related: 1 in ATV/r, 4 in LPV/r; hyperbilirubinemia/jaundice: 2 in ATV/r, 0 in LPV/r; death: 0 in ATV/r, 1 in LPV/r; any AE: 61% in ATV/r, 50% in LPV/r.
LIVER LAB ABNORMALITIES
Liver function abnormalities, ALT/AST >200: 2% ALT, 2% AST for ATV/r; 1% ALT, 2% AST for LPV/r; ALT or AST: 4% ATV/r, 2% LPV/r. total bilirubin: 5% ATV/r, 2% LPV/r.
--Liver Function Abnormalities (ALT/AST >200) when ALT or AST were >40 at baseline (n=34 ATV/r, 33 LPV/r): ALT - 9% ATV/r, 6% PV/r; AST: 9% ATV/r, 6% LPV/r; ALT or AST: 12% ATV/r, 6% LPV/r.
LIPIDS. Median values and Changes From Baseline in Lipid Parameters at month 12
--Median TG decreased on ATV/r from 181 to 145 and increased on LPV/r from 191 to 202;
--Total chol decreased on ATV/r from 202 to 193 and on LPV/r increased from 205 to 207.
--LDL-C on ATV/r increased from 107 to 111 and on LPV/r remained the same at 111.
--HDL-C changed from 50 to 46 on ATV/r and from 49 to 46 on LPV/r.
LIPIDS. Percentage above NCEP treatment recommendations at baseline and through month 12.
--TG >500: on ATV/r, 3% at baseline, 4% at mo 12 (+1%); on LPV/r, 10% at baseline, 17% at mo 12 (+7%).
--Total chol >240: on ATV/r, 23% at baseline, 20% at month 12 (-3%); on LPV/r, 20% at baseline, 26% at mo 12 (+6%);
--LDL>130: on ATV/r, 20% at baseline, 25% at mo 12 (+5%); on LPV/r, 20% at baseline, 30% at mo 12 (+10%);
--HDL-C <40: on ATV/r, 16% at baseline, 32% at mo 12 (+16%); on LPV/r, 21% at baseline, 29% at mo 12 (+8%).
No significant changes were obseved in Lipid Lowering Agents (LLA) usage during the follow-up in both arms