A Comparison of Dyslipidemias Associated with Either Lopinavir/Ritonavir- or Indinavir/Ritonavir-based Antiretroviral Therapy

Lopinavir/ritonavir/LPV/r (Kaletra) and indinavir/ritonavir/IDV/r are among the more commonly used dual protease inhibitor (PI)-based combinations. Factors that may influence selection of one approach over another include treatment history, genotypic resistance testing, pill burden, and adverse effects.

Antiretroviral-mediated dyslipidemias and associated clinical outcomes are important considerations as patients with HIV live longer. Differences among agents with respect to lipid profile may therefore be a determining factor in the selection of antiretroviral regimens, especially for patients with other risk factors for coronary heart disease.

Both IDV/r and LPV/r have been associated with adverse changes in lipid profile relative to boosted saquinavir in 2 separate randomized trials. However, data comparing the potential for dyslipidemia between IDV/r and LPV/r are limited to a single retrospective study of antiretroviral-naive patients, and no data are available in the treatment-experienced population.

The primary purpose of this retrospective cohort study was to evaluate and compare the lipid profile (total cholesterol and triglycerides) of patients receiving LPV/r- or IDV/r-based regimens.

IDV/r and LPV/r were initiated by 24 and 21 patients, respectively. At baseline, all patients in the IDV/r group were antiretroviral experienced, whereas 5 of the patients starting LPV/r-based therapy had been previously antiretroviral naive.

No significant differences were found between the IDV/r and LPV/r groups with respect to several prognostic variables associated with the onset of coronary artery disease and dyslipidemia, including age (41.6 vs. 42.4 years), the presence of at least 1 risk factor for heart disease such as smoking, hypertension, or diabetes mellitus (37.5 vs. 23.8%), concurrent use of stavudine (45.8 vs. 42.9%), or concurrent use of other medications that can potentially increase lipids (70.8 vs. 61.9%).

However, patients on IDV/r had a significantly longer cumulative exposure to HAART relative to LPV/r patients (3.9 vs. 2.8 years; P = 0.05). In addition, patients starting LPV/r had a significantly higher mean baseline viral load (4.6 vs. 3.1 log₁₀ copies/mL; P < 0.01) and lower mean baseline CD4⁺ cell count (125 vs. 352 cells/mm³; P < 0.01) relative to patients starting IDV/r.

At 12 months of follow-up, no significant differences were seen between IDV/r and LPV/r with respect to changes in serum lipids in this small cohort of HIV-positive patients. Results of a previously published retrospective study comparing IDV/r and LPV/r noted higher serum total cholesterol levels in the IDV/r group at month 3 and month 12 of the analysis. That cohort differed from the one reviewed here, however, in that the patients studied were all antiretroviral naive. As well, it was unclear from the data if the 2 groups were well balanced with respect to baseline characteristics that may be predisposed to elevations in serum lipids.

The authors conclude, “Comparative randomized trials of IDV/r and LPV/r are necessary to fully elucidate the virologic, immunologic, and metabolic profiles of each approach.”

02/11/05

Reference
T Antoniou and others. A Comparison of Dyslipidemias Associated With Either Lopinavir/Ritonavir- or Indinavir/Ritonavir-Based Antiretroviral Therapy. Journal of Acquired Immune Deficiency Syndromes 37(5): 1666-1667. December 15, 2004.