Changes in lipids and lipoprotein particle concentrations after interruption of antiretroviral therapy

Abstract

Background: The effect of interruption of antiretroviral therapy (ART) on lipoprotein particle subclasses has not been studied. We examined short-term changes in lipids and lipoprotein particles among 332 HIV-infected individuals randomized to interrupt or continue ART in the "Strategies for Management of Antiretroviral Therapy" trial.

Methods: Lipids and lipoprotein particles measured by nuclear magnetic resonance spectroscopy were compared between randomized groups at month 1; associations with inflammatory and coagulation markers (high sensitivity C-reactive protein; interleukin 6; amyloid A; amyloid P; D-dimer; prothrombin fragment 1 + 2) were assessed.

Results: Compared with continuation of ART, treatment interruption resulted in substantial declines in total, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, and triglyceride, at month 1 but had little net effect on total/HDL cholesterol ratio [baseline-adjusted mean difference [95% confidence interval (CI)] interruption versus continuation arms: -0.10 (-0.59 to 0.38); P = 0.67]. ART interruption resulted in declines in total, large, and medium very low density lipoprotein (VLDL) particle concentrations (VLDL-p) and total and medium HDL-p. However, there was no change in small HDL-p [baseline-adjusted percentage difference between arms: -4.6% (-13.1%, +5.1% ); P = 0.35], small LDL-p [-5.0% (-16.9%, +8.6%); P = 0.45], or other LDL-p subclasses. Changes in lipid parameters on ART interruption did not differ according to baseline ART class (protease inhibitor versus non-nucleoside reverse transcriptase inhibitor) but were negatively associated both with changes in HIV viral load and with changes in inflammatory and coagulation markers, particularly D-dimer.

Conclusions: These results suggest that ART interruption does not favorably influence overall lipid profile: there was little net effect on total/HDL cholesterol ratio, and no change in small LDL-p or small HDL-p, the lipoprotein particle subclasses most consistently linked to coronary risk. Short-term declines in lipid parameters after ART interruption were not associated with class of ART and may be linked to increases in viral replication, inflammation and coagulation.

Trial registration: ClinicalTrials.gov NCT00027352.

Figures

FIGURE 1

Mean changes from baseline in lipids according to randomized group, among 332 patients on antiretroviral therapy at baseline. (1) TC; (2) LDL cholesterol; (3) HDL cholesterol; (4) total/HDL cholesterol ratio (v) Log TG. DC arm represented by closed triangles; VS arm represented by open circles. Minimum denominators at months 0, 1, 2, 4, 8 are 156, 155, 142, 130, 107 for DC arm and 176, 175, 159, 149, 123 for VS arm.