Lipodystrophy-Associated Metabolic Syndrome in Patients With HIV

People with HIV have an increased risk for glucose and lipid disorders, including insulin resistance, glucose intolerance, type 2 diabetes, dyslipidemia, and lipodystrophy (ie, lipoatrophy or lipohypertrophy).3,6 Metabolic disorders in the HIV population likely arise from a combination of traditional risk factors, HIV-related factors, and adverse ART-related effects.3,6 Drugs used to treat various comorbidities may also contribute to metabolic dysregulation.3 Older combination ART regimens are associated with a greater risk for glucose or lipid abnormalities than newer regimens.3 Metabolic disease increases the risk for cardiovascular disease in people with HIV, who already have a greater risk for cardiovascular-related morbidity and mortality than the general population.3,6 There are no guidelines for managing metabolic disorders in people with HIV.3 Generally, the approach is the same as that used for the general population but with consideration of potential drug-drug interactions in patients using ART. Photo Credit: Carolina Biological.

People with HIV have an increased risk for glucose and lipid disorders, including insulin resistance, glucose intolerance, type 2 diabetes, dyslipidemia, and lipodystrophy (ie, lipoatrophy or lipohypertrophy).3,6 Metabolic disorders in the HIV population likely arise from a combination of traditional risk factors, HIV-related factors, and adverse ART-related effects.3,6 Drugs used to treat various comorbidities may also contribute to metabolic dysregulation.3 Older combination ART regimens are associated with a greater risk for glucose or lipid abnormalities than newer regimens.3

Metabolic disease increases the risk for cardiovascular disease in people with HIV, who already have a greater risk for cardiovascular-related morbidity and mortality than the general population.3,6 There are no guidelines for managing metabolic disorders in people with HIV.3 Generally, the approach is the same as that used for the general population but with consideration of potential drug-drug interactions in patients using ART.

Photo Credit: Carolina Biological.

Researchers assessed the effect of lipodystrophy-associated metabolic syndrome on oxidative stress and inflammatory processes in patients with HIV infection.

In patients with HIV infection and metabolic syndrome (MS), those with lipodystrophy (LD) receiving protease inhibitor (PI)-based antiretroviral therapy (ART) regimens for at least 6 months were more likely to experience worsening inflammatory processes and oxidative stress. These findings were published in Enfermedades Infecciosas y Microbiología Clínica.

Patients (N=243) diagnosed with HIV infection and MS were enrolled in this study between 2011 and 2012 at the Reginal Hospital Carlos Haya in Spain. The researchers assessed the effect of different ART regimens on immune system activation oxidative stress between patients with vs without LD. Atherogenic index of plasma (AIP) and Framingham risk scores were calculated to estimate patients’ cardiovascular risk.

Among patients  with (n=119) and without (n=124) LD included in the analysis, 39.5% and 45.16% were men, the mean age was 43.5±7.1 and 43.4±10.9 years, and the mean BMI was 28.5±7.6 and 24.3±6.1 kg/m2, respectively. In regard to cardiovascular risk, the mean AIP score was similar among patients with vs without LD (4.4±0.8 vs 4.3±1.1), but mean Framingham risk scores were increased among those with LD (6.1%±5.1% vs 3.5%±4.8%; P =.014). Compared with patients without LD, those with LD had increased mean systolic blood pressure measurements and HIV viral loads and decreased mean lymphocyte CD4 counts and CD4/CD8 ratios (all P <.001).

Further comparisons between patients with vs without LD showed that inflammation and oxidative stress variables, including interleukin (IL)-6, IL-8, carbonylated proteins, and lipid peroxidation were significantly increased among those with LD. However, patients with LD had decreased adiponectin, catalase activity, glutathione peroxidase activity, glutathione reductase activity, leptin, superoxide dismutase activity, and total antioxidant capacity (all P £.034).

For patients with LD, AIP scores were correlated with C-reactive protein (r, 0.333), carbonylated proteins (r, 0.900), catalase activity (r, -0.812), glutathione reductase activity (r, -0.999), and total antioxidant capacity (r, -0.825). Further analysis showed that Framingham risk scores among these patients were correlated with glutathione peroxidase activity (r, -0.886), and total antioxidant capacity (r, -0.620; all P <.05).

For patients without LD, AIP scores were correlated with adiponectin (r, 0.475), C-reactive protein (r, 0.333), catalase activity (r, -0.414), glutathione peroxidase activity (r, -0.869), and glutathione reductase activity (r, -0.742). Framingham risk scores among these patients were correlated with IL-6 (r, 0.284), C-reactive protein (r, 0.438), catalase activity (r, -0.264), and total antioxidant capacity (r, -0.620; all P £.05).

Stratified by ART regimens, patients with LD receiving PI-based ART had the lowest high-density lipoprotein cholesterol and highest triglyceride levels, as well as a significantly increased risk for cardiovascular events.

This study was limited by the relatively short duration of ART among the patients.

According to the researchers, these findings indicate “…a clear contribution of fat redistribution and metabolic disturbances to inflammatory process and oxidative stress in HIV-1 infected patients…”

Reference

González-Domenech CM, Plaza-Andrades IJ, Garrido-Sanchez L, Queipo-Ortuño MI. Synergic effect of metabolic syndrome and lipodystrophy on oxidative stress and inflammation process in treated HIV-patients. Enferm Infecc Microbiol Clin. 2022;40(6):310-316. doi:10.1016/j.eimce.2020.11.026