Longitudinal changes in serum lipids among HIV‐infected men on highly active antiretroviral therapy

Abstract

ObjectiveThe aim of the study was to describe longitudinal changes in serum lipids among HIV-infected men receiving highly active antiretroviral therapy (HAART) with long-term follow-up. MethodsA total of 304 HIV-infected men who initiated HAART and who had serum lipid measurements prior to and for up to 7 years after HAART initiation were identified from the Multicenter AIDS Cohort Study (MACS). Mean levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were examined at biannual time-points. ResultsSignificant lipid changes were seen within 0.5 years of HAART initiation but increases in TC ( 1 1.09 mmol/L), LDL-C ( 1 0.57 mmol/L), HDL-C ( 1 0.16 mmol/L) and non-HDL-C ( 1 0.91 mmol/L) reached peak levels 2-3 years after HAART initiation. Declines in serum TC, LDL-C and non-HDL-C in subsequent years occurred concurrently with a substantial increase in use of lipid-lowering medications (from 1% usage pre-HAART to 43% 6-7 years after HAART initiation) but the proportion of men who either were treated with cholesterol-lowering medication or had elevated cholesterol levels (45.18 mmol/L) did not change during the 2-7-year interval after HAART. Mean HDL-C also decreased after 2-3 years and was low (o1.04 mmol/L) in 55% of HIV-infected men 6-7 years after HAART initiation. ConclusionsAtherogenic serum lipids increased early after the initiation of HAART, peaked at 2-3 years and remained high or required treatment thereafter. Low HDL-C levels persisted in the majority of men. The long-term effects of lipid abnormalities on cardiovascular risk and the effectiveness and toxicity of prolonged use of lipid-lowering medications in combination with HAART are not known.Keywords: cohort studies, dyslipidemia, HAART, HIV-1, HIV infection Introduction HIV-1 infection has been associated with reductions in serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) and with elevations in triglycerides (TG) observed later in the disease course [1][2][3]. Use of single or dual nucleoside reverse transcriptase inhibitors (NRTIs) was not associated with significant changes in serum lipid levels. However, within 2 years of the widespread availability of potent protease inhibitor (PI)-based highly active antiretroviral therapy (HAART), there were numerous reports of moderate to severe changes in serum lipids as well as other metabolic alterations [4][5][6][7][8][9][10][11][12]. These observations were initially anecdotal or based on limited case series, but in recent years large randomized clinical trials of HAART have routinely included prospective measurement of serum lipids [13,14].Several important questions regarding the impact of serum lipid abnormalities in HAART-treated individuals remain unanswered. The incidence of cardiovascular events among HAART recipients has been assessed in several large cohort and database studies [15][16][17][18][19]. In aggregate, these studies suggest a small but sig...

HAART-Associated Dyslipidemia Varies by Biogeographical Ancestry in the Multicenter AIDS Cohort Study

“…Contrary to previous findings, HAART that contained a PI had significant effects only on TRIG and HDL-C levels. 6,8,9,15,52 Also, while these were statistically significant, only TRIG levels seemed to be substantially affected by PI/ HAART, with an associated higher level of 35.3 mg/dl. In contrast, the effects of PI/HAART were associated with a 3.2 mg/dl lower HDL-C level.…”

“…5 Yet drug-specific metabolic side effects such as lipodystrophy and dyslipidemia have been reported in HIV-1-seropositive patients receiving HAART. [6][7][8][9][10][11][12][13][14][15] These drug-related side effects augment the aberrant metabolic state associated with HIV-1 infection. The overriding clinical concern is that these metabolic alterations may be associated with an increased risk of cardiovascular disease (CVD) and myocardial infarction in this population.…”

Interferon-Free Treatment of Hepatitis C Virus in HIV/Hepatitis C Virus-Coinfected Subjects Results in Increased Serum Low-Density Lipoprotein Concentration

“…3,[24][25][26] Chronic HIV infection and treatment with ARVs are both associated with dyslipidemia, and cardiovascular risk is often modulated by the administration of LDL-lowering statin therapy. 1,2,4,27,28 Interestingly, the phenotypes of low LDL associated with HCV and hypercholesterolemia associated with HIV are often attenuated in the setting of HIV/HCV coinfection. [5][6][7][8]10 Treatment of chronic HCV infection is now possible with interferon (IFN)-free regimens composed of directly acting antiviral (DAA) agents that directly inhibit viral proteins.…”

“…[1][2][3][4][5][6][7][8][9][10][11][12][13] HCV infection is associated with lipid and lipoprotein metabolism disorders including hepatic steatosis, hypobetalipoproteinemia, and hypocholesterolemia.…”

Mg supplementation attenuates ritonavir-induced hyperlipidemia, oxidative stress, and cardiac dysfunction in rats

“…With the introduction of protein inhibitors (PIs) in the mid 1990s, HIV-1 replication in the patients was shown to be dramatically reduced, and currently, to the extent that HIV-1 infection has become a more manageable disease (20,23). However, along with the chronic use of PIs, significant metabolic side effects of hyperlipidemia, tissue lipodystrophy, and insulin resistance may result (18,42). Hyperlipidemia may contribute to the increased atherosclerotic vascular disease, resulting in endothelial and cardiac dysfunction (18,19).…”