A switch in therapy to a reverse transcriptase inhibitor sparing combination of lopinavir/ritonavir and raltegravir in virologically suppressed HIV-infected patients: a pilot randomized trial to assess efficacy and safety profile: the KITE study

Abstract

A nucleoside reverse transcriptase inhibitor (NRTI) backbone is a recommended component of standard highly active antiretroviral therapy (sHAART). However, long-term NRTI exposure can be limited by toxicities. NRTI class-sparing alternatives are warranted in select patient populations. This is a 48-week single-center, open-label pilot study in which 60 HIV-infected adults with plasma HIV-1 RNA (<50 copies/ml) on sHAART were randomized (2:1) to lopinavir/ritonavir (LPV/r) 400/100 mg BID+raltegravir (RAL) 400 mg BID switch (LPV-r/RAL arm) or to continue on sHAART. The primary endpoint was the proportion of subjects with HIV-RNA<50 copies/ml at week 48. Secondary efficacy and immunologic and safety endpoints were evaluated. Demographics and baseline lipid profile were similar across arms. Mean entry CD4 T cell count was 493 cells/mm(3). At week 48, 92% [95% confidence interval (CI): 83-100%] of the LPV-r/RAL arm and 88% (95% CI: 75-100%) of the sHAART arm had HIV-RNA<50 copies/ml (p=0.70). Lipid profile (mean ± SEM, mg/dl, LPV-r/RAL vs. sHAART) at week 24 was total-cholesterol 194 ± 5 vs. 176 ± 9 (p=0.07), triglycerides 234 ± 30 vs. 133 ± 27 (p=0.003), and LDL-cholesterol 121 ± 6 vs. 110 ± 8 (p=0.27). There were no serious adverse events (AEs) in either arm. Regimen change occurred in three LPV-r/RAL subjects (n=1, due to LPV-r/RAL-related AEs) vs. 0 in sHAART. There were no differences between arms in bone mineral density, total body fat composition, creatinine clearance, or CD4 T cell counts at week 48. In virologically suppressed patients on HAART, switching therapy to the NRTI-sparing LPV-r/RAL combination produced similar sustained virologic suppression and immunologic profile as sHAART. AEs were comparable between arms, but the LPV-r/RAL arm experienced higher triglyceridemia.

Figures

FIG. 1.

Consort diagram of the progress through the phases (enrollment, treatment allocation, follow-up, and data analysis) of a parallel randomized trial of two arms [the lopinavir/ritonavir (LPV/r) 400/100 mg BID+raltegravir (RAL) 400 mg BID switch or continue standard highly active antiretroviral therapy (sHAART)].

FIG. 2.

Longitudinal changes in the percentages of patients with undetectable plasma viral load (HIV-RNA(A). The time-trend lines are the model-based estimates obtained from a generalized estimating equations analysis of repeated binary responses within patients. The vertical bars are the 95% confidence intervals. The numbers provided at the bottom of the plot indicate the number of patients with data at each time point. (B) Estimates of the cumulative percentage of patients without virologic failure or a regimen change (event-free treatment failure) by treatment group (p=0.77, log-rank test). The numbers provided at the bottom of the plot indicate the number of patients that remain at risk.

FIG. 3.

Longitudinal changes in mean total cholesterol (mg/dl; A), triglycerides (mg/dl). (B) Triglycerides were significantly higher in the lopinavir/ritonavir-raltegravir (LPV-r/RAL) group at 24 weeks (p=0.05) but not at week 48 (p=0.61), HDL (mg/dl; C), LDL (mg/dl; D), CD4 T cell count (cells/mm3; E), and creatinine clearance (ml/min; F) by treatment arm. The time trend lines are the model-based means obtained from a repeated-measures analysis. The vertical bars are the 95% confidence intervals.

FIG. 4.

Longitudinal changes in mean body fat composition (total fat (kg; A), trunk fat (kg; B), arm fat (kg; C), leg fat (kg; D), and bone mineral density (pelvis density, g/cm2; E and spine density g/cm2; F) by treatment arm. The time trend lines are the model-based means obtained from a repeated-measures analysis. The vertical bars are the 95% confidence intervals.