Altered relationship of plasma triglycerides to HDL cholesterol in patients with HIV/HAART-associated dyslipidemia: Further evidence for a unique form of Metabolic Syndrome in HIV patients

Abstract

Introduction Plasma triglycerides (TG) and HDL-C are inversely related in Metabolic Syndrome (MetS), due to exchange of VLDL-TG for HDL-cholesteryl esters catalyzed by cholesteryl ester transfer protein (CETP). We investigated the relationship of TG to HDL-C in highly-active antiretroviral drug (HAART)-treated HIV patients. Methods Fasting plasma TG and HDL-C levels were compared in 179 hypertriglyceridemic HIV/HAART patients and 71 HIV-negative persons (31 normotriglyceridemic (NL) and 40 hypertriglyceridemic due to type IV hyperlipidemia (HTG)). CETP mass and activity were compared in 19 NL and 87 HIV/HAART subjects. Results Among the three groups, a plot of HDL-C vs. TG gave similar slopes but significantly different y-intercepts (9.24 ± 0.45, 8.16 ± 0.54, 6.70 ± 0.65, sqrt(HDL-C) for NL, HIV and HTG respectively; P<0.001); this difference persisted after adjusting HDL-C for TG, age, BMI, gender, glucose, CD4 count, viral load and HAART strata (7.18 ± 0.20, 6.20 ± 0.05 and 4.55 ± 0.15 sqrt(HDL-C) for NL, HIV and HTG, respectively, P <0.001). CETP activity was not different between NL and HIV, but CETP mass was significantly higher in HIV (1.47 ± 0.53 compared to 0.93 ± 0.27 μg/mL, P<0.0001), hence CETP specific activity was lower in HIV (22.67 ± 13.46 compared to 28.46 ± 8.24 nmol/μg/h, P=0.001). Conclusions Dyslipidemic HIV/HAART patients have a distinctive HDL-C plasma concentration adjusted for TG. The weak inverse relationship between HDL-C and TG is not explained by altered total CETP activity; it could result from a non-CETP-dependent mechanism or a decrease in CETP function due to inhibitors of CETP activity in HIV patients’ plasma.

HIV therapy, metabolic and cardiovascular health are associated with glomerular hyperfiltration among men with and without HIV infection

“…In the general population, proteinuria and impaired kidney function related to these conditions can be preceded by glomerular hyperfiltration, in which the glomerular filtration rate (GFR) increases to above normal levels [7–11], due to compensatory hemodynamic alterations within the kidney. Metabolic dysfunction characterized by impaired fasting glucose [12], diabetes mellitus [9,11,13], hypertension, and obesity [9] -conditions for which HIV-infected persons receiving HAART are at higher risk [14,15] - have also been linked to hyperfiltration.…”

Metabolic Syndrome, Diabetes, and Cardiovascular Risk in HIV

“…Studies from the general population have reported a link between cholesteryl ester transfer protein (CETP) activity and metabolic syndrome or DM. 33–35 Vu et al 36 found little difference in the CETP activity in 31 healthy adults compared to 179 HIV-infected adults from the Heart Positive Study who were on a stable HAART regimen for at least 6 months and had mean fasting triglyceride levels of 321 ± 194 mg/dL. By contrast, they observed significantly different HDL-C levels—highest in controls, intermediate in HIV-infected and lowest in a group of 40 patients with type IV high triglyceride group.…”

Perfil Metabólico De Portadores Do Hiv - Hospital De Clínicas De Curitiba

“…2/15 (13,33) 0/15 ( -) 0,2500 (5) TRIGLICERÍDEOS (n) 16 0,8065 (3) Média ± DP (2) Média ± DP (1) 6,80 ± 3,86…”

“…Além do uso de antirretrovirais, outros fatores têm sido associados às alterações metabólicas em portadores do HIV: fatores específicos do vírus, mecanismos inflamatórios relacionados com a infecção e/ou seu tratamento, ativação crônica do sistema imunológico e predisposição genética 3 . Ainda assim, a contribuição relativa à TARV e aos efeitos da própria doença na gênese dessas alterações não está bem definida na literatura.…”