Antiretroviral therapy in HIV‐positive men is associated with increased apolipoprotein CIII in triglyceride‐rich lipoproteins

Abstract

Dyslipidaemia has become a common problem in HIV disease, especially in patients on current antiretroviral therapy. However, the pathogenic mechanisms involved are not well understood or documented using conventional lipid measurements. MethodsUsing a cross-sectional design, the prevalence of abnormal standard lipid measurements and novel biomarkers for abnormal lipid metabolism was determined in 271 HIV-positive men from two HIV clinics in Atlanta, GA, USA. ResultsA total of 147 men were treated with protease inhibitors (PIs) for 43 months (54%), 84 were treated with nonnucleoside reverse transcriptase inhibitors (NNRTIs) for 43 months (31%) and 40 had not received antiretroviral therapy in the past 3 months (15%). Patients being treated with a PI had higher total cholesterol and triglyceride (TG) levels than patients on no therapy (Po0.05 for each). Patients in the NNRTI group had higher TG, lower high-density lipoprotein (HDL) levels, and higher low-density lipoprotein (LDL) levels than patients on no therapy (Po0.05 for each). Patients treated with either PIs or NNRTIs were more likely to have higher apolipoprotein CIII (apoCIII) levels (Po0.05 for each) than patients on no therapy. Elevated TG was associated with disproportionably elevated apoCIII levels in both treatment groups. ConclusionsIn this cross-sectional study of HIV-infected men, either PI or NNRTI therapy elevated levels of TG and apoCIII. Higher concentrations of apoCIII in apoB-containing lipoproteins [very low-density lipoproteins (VLDLs), intermediate density lipoprotein (IDL) and LDLs] have been predictive of an increased incidence of coronary events in clinical trials and more rapid progression of coronary lesions measured by angiography. These findings, on a background of an older population with additional risk factors of smoking and diabetes, portend future atherosclerotic events in these patients.

HIV infection and high density lipoprotein metabolism

“…Higher activity of CETP, especially when associated with hypertriglyceridemia, would increase the transfer of cholesteryl esters from HDL to apoB-containing lipoproteins. Consistent with this finding, the ratio of cholesterol to apoA-I in HDL was 50% lower in HIV-infected patients, indicating the presence of cholesterol poor (and presumably triglyceride-rich) HDL particles, a finding consistent with that of Rimland et al [21]. Moreover, in HIV-infected patients, the level of HDL-C correlated negatively with CETP levels, suggesting that the higher activity of CETP is an important contributor to the low HDL-C levels.…”

Antiretroviral Therapy in HIV-Positive Women Is Associated With Increased Apolipoproteins and Total Cholesterol

“…These abnormalities are similar to our previous study in men from the same patient population. 5 These findings suggest impaired metabolism of triglyceriderich lipoproteins. On a background of an older population with additional risk factors of smoking, obesity, and diabetes, this may be associated with future atherosclerotic events in these patients.…”

“…In addition, little data are available on antiretroviral-associated changes in newer markers of lipid metabolism, such as specific apolipoproteins (apo B, apo E, and apo C-III) and lipoprotein particle size. 5,10,11 These lipoprotein subclasses, as defined by particle concentration and size, have different atherogenic risk. Further elucidating the changes produced by antiretroviral therapy will help define the mechanisms underlying the lipoprotein changes.…”

Antiretroviral therapy-induced lipid alterations: in-vitro, animal and human studies

“…In HIV-infected patients, levels of apoC-III correlate with plasma triglycerides [25], with apoC-III levels in protease-inhibitor-treated males almost double that of controls [26]. The presence of apoC-III polymorphisms, such as -455T>C, -482C>T and SstI (3238C>G) -common in HIV-infected populations [27,28] -has been associated with hypertriglyceridaemia [24].…”