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

Abstract

Background 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- and low-density lipoprotein particle concentrations (HDL-P and LDL-P) and apolipoprotein (Apo) levels are not well described. Methods In a subgroup of participants not taking ART at study entry who were randomized in the Strategies for Management of Antiretroviral Therapy (SMART) to immediately initiate ART (‘VS group’) or to defer it (‘DC group’), lipoprotein particle concentrations and ApoA1 and ApoB levels were measured at baseline and at 2 and 6 months following randomization. Results Compared to DC group (n=126), HDL-P and ApoA1 levels increased among VS participants (n=128) after starting ART. At 6 months, VS participants had 13% higher total HDL-P (p < 0.001) and 9% higher ApoA1 (p < 0.001). LDL-P, VLDL-P, and ApoB did not differ significantly between the VS and DC groups. Among VS participants, predictors of HDL-P and ApoA1 increases included baseline levels of hsCRP and IL-6, but not HIV RNA level, CD4 count or traditional CVD 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). Conclusion 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.

Association of Apolipoprotein B and Nuclear Magnetic Resonance Spectroscopy–Derived LDL Particle Number with Outcomes in 25 Clinical Studies: Assessment by the AACC Lipoprotein and Vascular Diseases Division Working Group on Best Practices

“…A consistent role of apo B or LDL-P in this grouping is not evident because of the number of outcomes in which both parameters were not statistically significant; however, in instances in which both were significant, both were generally affected to the same extent (35)(36)(37)(38)(39).…”

The feature of Metabolic Syndrome in HIV naive patients is not the same of those treated: Results from a prospective study

“…The association between HIV infection and low HDL is well established [29,30]. A recent study [31] suggested that HIV-associated dyslipidemia was, partially at least, related to chronic inflammation, and that the effect of HAART on HDL changes could be mediated by suppressing inflammation. In fact, inflammation induces major changes in HDL levels and composition.…”

Outcomes after reinitiating antiretroviral therapy in children randomized to planned treatment interruptions

“…For example, growth, which is an important and often sensitive measure of successful treatment in children and youth, were comparable between PTI and cARTarms, and more recently we have reported no difference between cART and PTI arms in neurodevelopmental test scores performed cross-sectionally in the PENTA 11 children after the end of the trial [10]. Similarly, although a decline in total, low and high-density lipoprotein from baseline was seen in the first 12 weeks off ART among PTI children in the main trial [8], no differences in fasting lipids were observed between the two arms during longterm follow-up; in contrast, PTI was associated with increased low high-density lipoprotein levels in SMART [28].…”