Evolution of Blood Lipids and Risk Factors of Dyslipidemia Among People Living with Human Immunodeficiency Virus Who Had Received First-Line Antiretroviral Regimens for 3 Years in Shenzhen
Introduction Antiretroviral therapy (ART) has significantly improved the prognosis of people living with human immunodeficiency virus (HIV) (PLWH). However, ART is associated with metabolic complications, including dyslipidemia, which can increase the risk of cardiovascular disease (CVD). PLWH have a higher risk for CVD compared to the general population, and the risk of myocardial infarction (MI) increases with exposure to certain ART regimens. Understanding the evolution of blood lipids and identifying risk factors for dyslipidemia in PLWH on long-term ART is crucial for optimizing treatment and reducing CVD risk.
Study Design and Methods This retrospective cohort study included 7623 ART-naïve adult PLWH who sought care at the Third People’s Hospital of Shenzhen from January 2014 to December 2018. Inclusion criteria were: age ≥15 years, confirmed HIV diagnosis, ART duration ≥3 months, and at least one follow-up measurement of blood lipids. Exclusion criteria included presence of tumors, autoimmune diseases, active infections, pregnancy or lactation, and no lipid testing within 6 months of ART initiation. The first-line ART regimens included combinations of two nucleoside reverse transcriptase inhibitors (NRTIs) and one non-nucleoside reverse transcriptase inhibitor (NNRTI) or a boosted protease inhibitor (PI). The regimens were: tenofovir disoproxil fumarate (TDF) + lamivudine (3TC) + efavirenz (EFV), TDF + 3TC + ritonavir-boosted lopinavir (LPV/r), zidovudine (AZT) + 3TC + EFV, and AZT + 3TC + LPV/r.
Baseline Characteristics The study population consisted of 91.8% males with a mean age of 32 ± 10 years. The primary route of HIV transmission was men who have sex with men (MSM). Most patients had CD4 cell counts between 200 and 349 cells/mL, and 29.3% were in WHO HIV clinical stages III-IV. The most commonly used regimen was TDF + 3TC + EFV (87.6%), followed by AZT + 3TC + EFV (5.5%), TDF + 3TC + LPV/r (5.4%), and AZT + 3TC + LPV/r (1.5%).
Blood Lipid Levels at Baseline At baseline, the mean levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were 4.23 ± 0.85 mmol/L, 1.27 ± 0.29 mmol/L, and 2.54 ± 0.65 mmol/L, respectively. The median triglyceride (TG) level was 1.17 (IQR: 0.85–1.68) mmol/L. Higher levels of TC, TG, and LDL-C were observed in older patients, overweight and obese individuals, and those with heterosexual transmission. HDL-C levels were lower in males, overweight and obese individuals, and those with lower CD4 cell counts and higher HIV RNA loads.
Evolution of Dyslipidemia The study found that the rates of dyslipidemia varied among different ART regimens. The rate of hypertriglyceridemia (TG ≥1.70 mmol/L) was lower in patients receiving TDF + 3TC + EFV (22.4%) and AZT + 3TC + EFV (26.7%) compared to those receiving TDF + 3TC + LPV/r (50.9%) and AZT + 3TC + LPV/r (48.4%). Three months after ART initiation, TG levels increased significantly in all regimens, but the rates of hypertriglyceridemia decreased over time in PLWH receiving TDF + 3TC + EFV, TDF + 3TC + LPV/r, and AZT + 3TC + LPV/r, while it increased in those receiving AZT + 3TC + EFV.
The highest rate of hypercholesterolemia (TC ≥5.20 mmol/L) at baseline was found in PLWH treated with AZT + 3TC + LPV/r (28.2%), followed by AZT + 3TC + EFV (19.7%) and TDF + 3TC + EFV (11.4%). After ART initiation, hypercholesterolemia rates increased in all groups.
The highest rate of elevated LDL-C (LDL-C ≥3.37 mmol/L) at baseline was observed in PLWH receiving AZT + 3TC + LPV/r (17.7%), followed by AZT + 3TC + EFV (13.6%). After ART initiation, elevated LDL-C rates increased in PLWH receiving AZT + 3TC + LPV/r, AZT + 3TC + EFV, and TDF + 3TC + LPV/r, but remained low in those receiving TDF + 3TC + EFV.
The rate of decreased HDL-C (HDL-C <1.04 mmol/L) at baseline was highest in PLWH receiving TDF + 3TC + LPV/r (28.3%). Three months after ART initiation, the rates of decreased HDL-C decreased significantly in PLWH receiving TDF + 3TC + LPV/r and TDF + 3TC + EFV, but increased in those receiving AZT + 3TC + EFV.
Risk Factors for Dyslipidemia Multivariate analysis identified several risk factors for dyslipidemia. Compared to TDF + 3TC + EFV, the risks of elevated TG, TC, and LDL-C were higher with TDF + 3TC + LPV/r, AZT + 3TC + EFV, and AZT + 3TC + LPV/r. TDF + 3TC + LPV/r was also associated with a decreased HDL-C level. Female sex, older age, overweight, and obesity were independent risk factors for high TC. Male sex, older age, overweight, and obesity were risk factors for high TG. Overweight and obesity were risk factors for low HDL-C, while older age, overweight, and obesity were risk factors for low LDL-C. ART duration was also an independent factor for dyslipidemia, with higher risks of elevated TG, TC, and LDL levels observed at various time points after ART initiation.
Discussion This study highlights the impact of different ART regimens on lipid profiles in PLWH. TDF + 3TC + EFV was associated with a lower risk of dyslipidemia compared to other first-line free antiretroviral regimens in China. PIs, particularly LPV/r, were more likely to cause hypertriglyceridemia and hypercholesterolemia, while TDF had a lipid-lowering effect similar to statins. The findings suggest that TDF + 3TC + EFV is preferred for PLWH with dyslipidemia or cardiovascular risk factors, and regular monitoring of blood lipids is essential during ART.
In addition to ART, traditional risk factors such as older age, overweight, and obesity were significant contributors to dyslipidemia in PLWH. The study underscores the importance of comprehensive management of modifiable risk factors, including lifestyle interventions and potential use of lipid-lowering agents, to reduce CVD risk in this population.
Conclusion The incidence of dyslipidemia varies among different ART regimens, with TDF + 3TC + EFV having a lower risk compared to other first-line free antiretroviral regimens in China. Regular monitoring of blood lipids and management of modifiable risk factors are crucial for optimizing the long-term health outcomes of PLWH on ART.
doi.org/10.1097/CM9.0000000000001245
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