Prevalence of dyslipidemia and associated risk factors among Chinese people living with HIV

Dyslipidemia is a metabolic disorder with a higher prevalence among people living with human immunodeficiency virus (HIV) than that among the general population, and it significantly increases the risk of cardiovascular disease (CVD).[1] HIV infection can lead to dyslipidemia through persistent inflammation, immune activation, and direct effects on lipid metabolism.[1] The initiation of antiretroviral therapy (ART) can exacerbate dyslipidemia, often characterized by increased concentrations of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG), along with a decrease in the concentration of high-density lipoprotein cholesterol (HDL-C).[2] Additionally, traditional risk factors contribute to the development of dyslipidemia in this population.[3] Previous studies on dyslipidemia and its associated factors were conducted in various regions of China.[4–6] However, they were limited by the lack of large-scale data that were nationally representative, and they were conducted in controlled environments. The aim of our study was to investigate this issue in real-life clinical settings in a larger area. Our study involved 149 medical centers and covered all provincial administrative divisions in China with a high HIV prevalence. The patients enrolled in this study represent a diverse cross-section of the overall population of individuals infected with HIV in China. The inclusion criteria were a confirmed diagnosis of HIV infection and being registered in one of the participating hospitals. Sociodemographic and clinical data, along with blood samples for lipid and HIV-related tests, were collected by trained study staff. Dyslipidemia was defined according to the National Cholesterol Education Program Adult Treatment Panel III guidelines: TC concentration ≥5.20 mmol/L, HDL-C concentration <1.04 mmol/L, LDL-C concentration ≥3.37 mmol/L, or TG concentration ≥1.70 mmol/L.[7] The study was approved by the Institutional Review Board of the Chinese Center for Disease Control and Prevention (No. X220314682) and conducted in accordance with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from all participants. Statistical analyses were conducted using SAS 9.4 (SAS Institute Inc., Cary, NC, USA) and R software (Version 4.2.2, https://www.r-project.org). Qualitative data were presented as rates or proportions (%), and between-group comparisons were made using the chi-squared test or Fisher’s exact test. Variables for multivariable analysis of dyslipidemia were selected based on clinical expertise, statistically significant variables upon univariate analysis, and collinearity between independent variables. A multivariable logistic regression model was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for the association between risk factors and dyslipidemia, with a P-value <0.05 indicating statistical significance. This cross-sectional study included 5211 participants infected with HIV, with a mean ± standard deviation age of 43.2 ± 13.7 years. Overall, 79.9% (4163/5211) of participants were classified as being infected with HIV stages I–II. The median CD4 cell count was 408 (interquartile range [IQR], 232–621) cells/μL, and the median CD8 cell count was 836 (IQR, 581–1168) cells/μL. The numbers of participants with hypertension (77/5211, 1.5%), diabetes (60/5211, 1.2%), and CVD (39/5211, 0.8%) were relatively small. A total of 3121 participants had received prior ART, and 2090 were treatment-naïve [Supplementary Table 1, https://links.lww.com/CM9/C190]. The overall prevalence of dyslipidemia among individuals with an HIV infection was 75.5% (3933/5211). The prevalences of high TC, high TG, low HDL-C, and high LDL-C concentrations were 27.8% (1447/5211), 49.5% (2581/5211), 44.7% (2327/5211), and 18.3% (954/5211), respectively [Supplementary Table 2, https://links.lww.com/CM9/C190]. In this study, the overall prevalence of dyslipidemia among individuals with an HIV infection was twice as high as previously reported in the general Chinese population (35.6%).[3] Notably, we also observed a higher rate of dyslipidemia (73.6%) among antiretroviral-naïve patients than that in prior reports in China.[5,6,8] Our study revealed that smoking and having a high body mass index (BMI) were independent risk factors for dyslipidemia among treatment-naïve patients [Supplementary Table 3, https://links.lww.com/CM9/C190]. Therefore, the discrepancies between our study and previous studies may be attributed to the considerable proportion of smokers (27.1%, 567/2090) and individuals who were overweight or obese (31.1%, 639/2090) within the treatment-naïve group in this study. A meta-analysis of 51 studies from 2000 to 2014, involving 37,110 patients, linked ART to higher serum lipid concentrations and the risk of dyslipidemia.[9] Patients on ART had notably higher levels of TC, LDL-C, and TGs than the ART-naïve patients. The risks of hypercholesterolemia (pooled OR = 3.8, 95% CI: 3.1–4.7) and hypertriglyceridemia (pooled OR = 2.2, 95% CI: 1.7–2.9) were significantly greater among patients who had undergone ART.[9] In this study, the prevalence of dyslipidemia differed significantly between ART-naïve and ART-treated participants (73.3% [1532/2090] and 76.9% [2401/3121], respectively, P = 0.003). Logistic regression analysis revealed that ART was an independent risk factor for hypercholesterolemia (OR = 2.19, 95% CI: 1.49–3.21), hypertriglyceridemia (OR = 2.44, 95% CI: 1.80–3.32), and a high LDL-C concentration (OR = 2.73, 95% CI: 1.93–3.84) [Supplementary Table 4, https://links.lww.com/CM9/C190]. In our study, hypertriglyceridemia and low HDL-C were the most common abnormalities among patients with dyslipidemias, in line with the results of other studies in China and Ethiopia.[5,10,11] The prevalence of hypertriglyceridemia (49.5%) was comparable to those observed in a study in Singapore (45.5%) and the DAD study in Europe, Australia, and the United States (47.3%).[12,13] The elevated TG concentrations in people living with HIV (PLWH) are attributed to chronic immune activation and inflammation, which impair the oxidation of plasma-free fatty acids and promote hepatic re-esterification of TG.[2] A meta-analysis of 14 trials involving 21,023 people in sub-Saharan Africa between 2003 and 2014 revealed that ART was associated with a two-fold higher probability of hypertriglyceridemia (relative risk = 2.05, 95% CI: 1.51–2.77).[14] As expected, the prevalence of hypertriglyceridemia differed significantly between ART-naïve and ART-treated participants, with rates of 36.0% and 58.6% respectively. In addition to ART, this study demonstrated that a high BMI, duration of HIV infection >5 years, and a CD8 cell count ≥1000 cells/μL were also independent risk factors of hypertriglyceridemia. HDL-C reduction is common among PLWH, affecting up to 44.9% of patients in China.[5] In this study, the overall prevalence of a low HDL-C concentration was 44.7%. A significant difference in the prevalence of a low HDL-C concentration was observed between ART-naïve and ART-treated PLWH (53.3% vs. 38.9%, P <0.001), but we were unable to establish a direct association between ART and a low HDL-C concentration. Li et al[5] observed a normalization of HDL-C concentrations following ART treatment. They attributed this improvement in the lipid profile to two ART-induced effects: the suppression of viral replication and the restoration of immune function, which together promote a transition toward a less inflammatory physiological state. This interpretation may be relevant to our results. The HIV-1-specific viral protein Nef can directly block adenosine-triphosphate-binding cassette transporter A1-mediated cholesterol efflux to HDL particles; therefore, HIV infection results in a reduced HDL-C concentration.[15] The HDL-C concentration decreases significantly with the progression of HIV infection and is associated with the viral load. Furthermore, several studies have revealed a strong association between the CD4 cell count and dyslipidemia.[10,16,17] Advanced HIV disease is associated with T-cell proliferation, heightened T-cell activation, and increases in inflammatory cells and pro-inflammatory cytokines.[8] Those factors likely correlate to a lower nadir CD4 cell count.[18] We observed that a decreased CD4 count was linked to a higher prevalence of low HDL-C among patients with a CD4 cell count <500 cells/μL. The prevalence of a CD4/CD8 ratio ≥0.60 in treatment-naïve patients was inversely correlated with the prevalence of a low HDL-C concentration. Furthermore, we discovered that an advanced HIV stage and an HIV RNA viral load ≥104 copies/mL were both associated with a reduced HDL-C concentration. These results emphasize the correlation between dyslipidemia and HIV disease status. Apart from HIV-related factors, we demonstrated that being a man and being overweight or obese were also independent risk factors for a low HDL-C concentration. Evidence from epidemiological, genetic, and clinical studies strongly indicates that an increased LDL-C concentration is a major risk factor for atherosclerotic CVD and a primary target of lipid-lowering therapy.[1,3] A series of meta-analyses suggested that a reduction of 1 mmol/L in the LDL-C concentration achieved with statins yields a relative risk reduction (RRR) of major vascular events of approximately 21% and of all-cause mortality of approximately 10%.[1] The prevalence of a high LDL-C concentration was 18.3% among all participants in this study, 11.9% among treatment-naïve participants, and 22.6% among ART-treated participants. Logistic regression analysis revealed several risk factors of an increased LDL-C concentration: a history of ART (OR = 2.73, 95% CI: 1.93–3.84), being overweight (OR = 2.18, 95% CI: 1.02–4.66), being obese (OR = 3.19, 95% CI: 1.27–7.99), and having a CD8 cell count ≥1000 cells/μL (OR = 2.65, 95% CI: 1.50–4.68). These results were consistent with those in a meta-analysis and previous clinical studies.[5,9,12] ART has a dual effect on the lipid profiles of individuals with an HIV infection, providing both benefits and risks, as previously reported.[1] Among the various first-line ART regimens, the tenofovir disoproxil fumarate (TDF) + lamivudine (3TC) + efavirenz (EFV) regimen has a distinct impact on dyslipidemia rates and is preferred for HIV treatment owing to its efficacy and tolerability.[4] In our study of 3121 patients who had received ART, 56.5% (1763/3121) had previously received TDF + 3TC + EFV. Those on this regimen exhibited a significantly lower prevalence of dyslipidemia, including hypercholesterolemia, hypertriglyceridemia, and low HDL-C concentration than those on other regimens (P <0.05) [Supplementary Tables 5 and 6, https://links.lww.com/CM9/C190]. This result highlights the influence of specific ART regimens, such as TDF + 3TC + EFV, on lipid metabolism and the potential reduction in dyslipidemia risk among patients with an HIV infection who receive such regimens, consistent with previous research.[4,5] In conclusion, this study emphasized the considerable prevalence of dyslipidemia among Chinese PLWH and identified various risk factors linked to this condition. These results highlight the importance of regular monitoring of lipid concentrations among PLWH, especially those who exhibit the identified risk factors. Furthermore, interventions aimed at the reduction of dyslipidemia among PLWH should be tailored to address the unique risk factors in this population.