Inflammation predicts changes in high-density lipoprotein particles and apolipoprotein A1 following initiation of antiretroviral therapy

Abstract

The effects of HIV infection and antiretroviral therapy (ART) on usual lipid levels have been reported. The effects of initiating versus deferring ART on high-density and low-density lipoprotein particle (HDL-P and LDL-P, respectively) concentrations and apolipoprotein (Apo) levels are not well described. In a subgroup of participants not taking ART at study entry who were randomized in the Strategies for Management of Antiretroviral Therapy (SMART) trial to immediately initiate ART ('viral suppression group') or to defer it ('drug conservation group'), lipoprotein particle concentrations and ApoA1 and ApoB levels were measured at baseline and at 2 and 6 months following randomization. Compared with drug conservation group (n = 126), HDL-P and ApoA1 levels increased among viral suppression participants (n = 128) after starting ART. At 6 months, viral suppression participants had 13% higher total HDL-P (P < 0.001) and 9% higher ApoA1 (P < 0.001). LDL-P, very low density lipoprotein particle, and ApoB did not differ significantly between the viral suppression and drug conservation groups. Among viral suppression participants, predictors of HDL-P and ApoA1 increases included baseline levels of high-sensitivity C-reactive protein (hsCRP) and interleukin 6 (IL-6), but not HIV RNA level, CD4 cell count, or traditional cardiovascular disease risk factors. The effect of starting ART on changes in HDL-P and ApoA1 was greater for those with higher versus lower baseline levels of IL-6 (P = 0.001 and 0.08, respectively, for interaction) or hsCRP (P = 0.01 and 0.04, respectively, for interaction). HDL-P and ApoA1 increase following ART initiation, to a degree that depends on the degree of inflammation present at entry. These findings suggest that activation of inflammatory pathways contribute to HIV-associated changes in HDL.