Lipids, biomarkers, and subclinical atherosclerosis in treatment-naive HIV patients starting or not starting antiretroviral therapy: Comparison with a healthy control group in a 2-year prospective study

Abstract

Objective To assess the effect of HIV infection and combined antiretroviral therapy (c-ART) on various proatherogenic biomarkers and lipids and to investigate their relationship with subclinical atherosclerosis in a cohort of treatment-naive HIV-infected patients. Methods We performed a prospective, comparative, multicenter study of 2 groups of treatment-naive HIV-infected patients (group A, CD4>500 cells/μL, not starting c-ART; and group B, CD4<500 cells/μL, starting c-ART at baseline) and a healthy control group. Laboratory analyses and carotid ultrasound were performed at baseline and at months 12 and 24. The parameters measured were low-density lipoprotein (LDL) particle phenotype, lipoprotein-associated phospholipase A2 (Lp-PLA2), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), sCD14, sCD163, monocyte chemoattractant protein-1(MCP-1), and asymmetric dimethylarginine (ADMA). A linear mixed model based on patient clusters was used to assess differences in biomarkers between the study groups and over time. Results The study population comprised 62 HIV-infected patients (group A, n = 31; group B, n = 31) and 22 controls. Age was 37 (30–43) years, and 81% were men. At baseline, the HIV-infected patients had a worse LDL particle phenotype and higher plasma concentration of sCD14, sCD163, hs-CRP, and LDL-Lp-PLA2 than the controls. At month 12, there was an increase in total cholesterol (p = 0.002), HDL-c (p = 0.003), and Apo A-I (p = 0.049) and a decrease in sCD14 (p = <0.001) and sCD163 (p<0.001), although only in group B. LDL particle size increased in group B at month 24 (p = 0.038). No changes were observed in group A or in the healthy controls. Common carotid intima-media thickness increased in HIV-infected patients at month 24 (Group A p = 0.053; group B p = 0.048). Plasma levels of sCD14, sCD163, and hs-CRP correlated with lipid values. Conclusions In treatment-naive HIV-infected patients, initiation of c-ART was associated with an improvement in LDL particle phenotype and inflammatory/immune biomarkers, reaching values similar to those of the controls. HIV infection was associated with progression of carotid intima-media thickness.

Do All Integrase Strand Transfer Inhibitors Have the Same Lipid Profile? Review of Randomised Controlled Trials in Naïve and Switch Scenarios in HIV-Infected Patients

“…This increase was higher than expected for the intraindividual long-term biological variation, which was established in 6% for TC, 7.8% for LDL-c, 19.9% for TG, and 7.3% for HDL-c [32]. These increases may be considered a return of a healthier state in terms of lipids, as previously described in observational studies, and they may be related to decreases in inflammation and immune activation mediated by virological suppression [5,8]. However, when RAL and DTG (no data are available for BIC) were combined with TDF, no changes or even a tendency toward reducing lipid plasma concentrations were found in the trials.…”

“…Non-treated chronic HIV infection, as well as other chronic infections and inflammation conditions, is associated with an atherogenic lipid phenotype. This phenotype is characterized by changes in lipid concentrations, including decreased levels of high-density lipoprotein cholesterol (HDL-c), total cholesterol (TC), and increased levels of triglycerides (TG), as well as modifications in lipid composition and function [5][6][7][8]. The initiation of combined ART has been associated with lipid changes, which can be considered a return to a "healthy" state [5,8].…”

Inflammatory markers as correlates of body composition and grip strength among adults with and without HIV: A cross-sectional study in Ethiopia

“…Other studies have also reported higher CRP levels among individuals with HIV compared to individuals without HIV (21)(22)(23), but higher levels among individuals without HIV have also been observed (24). CRP levels observed in different studies varies remarkedly as it is affected by factors such as nutritional status, ART experience, and other chronic comorbidities or infections (10,21,(23)(24)(25). In the present study the median s-CRP was 2.08 mg/l in individuals with HIV and the CRP concentration increased with disease progression.…”

“…In the present study, the median CRP level was higher in individuals with HIV compared to individuals without HIV. Other studies have also reported higher CRP levels among individuals with HIV compared to individuals without HIV (21)(22)(23), but higher levels among individuals without HIV have also been observed (24). CRP levels observed in different studies varies remarkedly as it is affected by factors such as nutritional status, ART experience, and other chronic comorbidities or infections (10,21,(23)(24)(25).…”

Spatial Heterogeneity of Brain Lipids in SIV-infected Macaques Treated with Antiretroviral Therapy

“…Even though newer antiretrovirals do not elevate circulating lipids to the same extent, tenofovir prodrugs, including tenofovir alafenamide, increase cholesterol species (91). This occurs despite the known impact of HIV on diminishing total cholesterol levels (86,(92)(93)(94)(95). Conversely other ARTs, including raltegravir, dolutegravir, and bictegravir, have either a beneficial or minimal impact on the cholesterol profile after changing regimens from older protease inhibitors (86,96).…”