70aLB
Switching from Stable Lopinavir/Ritonavir-based to Raltegravir-based Combination ART Resulted in a Superior Lipid Profile at Week 12 but Did Not Demonstrate Non-Inferior Virologic Efficacy at Week 24
Joseph Eron*1, J Andrade2, R Zajdenverg3, C Workman4, D Cooper5, B Young6, X Xu7, B-Y Nguyen7, R Leavitt7, and P Sklar7
1Univ of North Carolina at Chapel Hill, US; 2Antinguo Hosp Civil de Guadalajara, Mexico; 3Hosp Escola Sao Francisco de Assis, Rio de Janeiro, Brazil; 4AIDS Res Initiative, Darlinghurst, Australia; 5Univ of New South Wales, Sydney, Australia; 6Denver Infectious Disease Consultants, CO, US; and 7Merck Res Labs, West Point, PA, US
Background: Ritonavir-boosted protease inhibitors
(PI) have become an essential part of ART; however, such treatment has been
associated with toxicities, particularly lipid abnormalities. Studies in
treatment-naive patients demonstrated that the HIV integrase inhibitor raltegravir
(RAL) in combination therapy with 2 NRTI is clinically effective and
well-tolerated with minimal effects on lipids.
Methods: SWITCHMRK 1 and 2 were parallel,
multicenter, double-blind, randomized, active-controlled studies in HIV+
patients who were virologically well controlled on a stable lopinavir/ritonavir
(LPVr) -based regimen. Patients who failed prior therapies and were suppressed
for ≥3 months were not excluded. Patients were randomized (1:1) to switch
LPVr to RAL (400 mg bid) or continue on LPVr (400/100 mg bid) while remaining
on the same background ART which included at least 2 NRTI (and no other PI);
randomization was stratified by duration of prior LPVr-based therapy (≤
or >1 year). Primary endpoints were: mean percentage change in lipids at
week 12; proportion of patients with HIV RNA <50 copies/mL at week 24; and
safety and tolerability as long as 24 weeks.
Results: In SWITCHMRK 2, 355 patients were
randomized and 354 treated; 176 switched to RAL, 178 remained on LPVr. Baseline
characteristics were generally well balanced; 81.9% of patients had LPVr-based
therapy >1 year before enrolling in the study. RAL was superior to LPVr for
the mean percentage change from baseline in total cholesterol (–12.41 vs 1.29, p
<0.001), triglycerides (–42.82 vs 8.20, < 0.001), and non-HDL-C (–14.77
vs 2.91, p <0.001) at week 12. HDL change was not significantly
different. At week 24, 154 of 175 (88.0%) vs 167 of 178 (93.8%) of patients had
HIV RNA <50 copies/mL in the RAL and LPVr groups, respectively; treatment
difference –5.8% (95%CI –12.2 to 0.22; NC = F). RAL did not demonstrate
non-inferiority of RAL as compared to LPVr based on the pre-defined margin of
–12%. Response varied by important demographic factors (data not shown). Clinical
adverse experiences of all severities, RAL vs. LPVr, (69.9% vs. 62.9%) and
drug-related adverse experiences (13.1% vs 19.7%) were similar.
Conclusions: In virologically suppressed patients on
LPVr-based therapy, switching to RAL was well tolerated and resulted in
improved lipid parameters at week 12, but did not demonstrate non-inferiority
with respect to HIV RNA <50 copies/mL at week 24 as compared to remaining on
LPVr. Factors associated with continued virologic suppression after switching
to RAL are being evaluated.
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