Prevalencia de ateromatosis subclínica en pacientes infectados por el virus de la inmunodeficiencia humana. Influencia de la coinfección por el virus de la hepatitis C

Resumen

The implementation of antiretroviral therapy in the HIV-infected population has increased the life expectancy of these patients, leading to an increase in traditional lifestyle and age-related vascular risk factors. These patients have an added vascular burden, attributed to HIV's own immune and inflammatory activity, dyslipidemia associated with viral infection and antiretroviral therapies, specifically protease inhibitors. Hepatitis C virus infection is often associated with HIV, and is also a risk factor for the development of subclinical atheromatosis and cardiovascular events. This study aims to assess the effect of HIV/HCV coinfection on the development of subclinical atheromatosis in patients without a previous cardiovascular event and determine the main factors associated with atherosclerotic plaque, both classical and HIV-specific. A cross-sectional, multicentre study was conducted on the cohort of HIV-infected and HIV/HCV-coinfected patients in the province of Huelva. The study was undertaken by the Lipid and Vascular Risk Unit of the Infanta Elena Hospital together with the Infectious Diseases Unit of the Infanta Elena and Juan Ramón Jiménez Hospital in Huelva. The clinical histories and analytical determinations of the 1208 HIV patients registered in the ACyH® database in October 2020 were reviewed. During the period between October 2020 and July 2021, 183 patients were included, who accepted their inclusion in the study and signed the informed consent. 57 (31.14 %) were women and the mean age was 51.84 years. 69 patients (37.70 %) had no atheromatous plaque and 114 (62.29 %) showed subclinical atheromatosis detected on ultrasound study. Subclinical atheromatosis was present in 62.29 % of HIVinfected patients in our cohort. Atherosclerotic plaque was mainly distributed in the carotid territory (83.32 %) where it was independently associated with older age and CD4/CD8 ratio < 0.7. The prevalence of femoral atheromatosis was 57.93 % and was related to older age, male sex and smoking. 41.2 % of patients had plaque in both vascular territories.HCV coinfection was significantly associated with the presence of subclinical atheromatosis, with plaque present in 73.8 % of coinfected and 55.9 % of monoinfected patients (p = 0.017). Protease inhibitor use was higher in the group with atherosclerotic plaque (70.6 % vs. 29.4 %; p = 0.009). Patients taking darunavir, atazanavir or lopinavir/ritonavir were found to have a non-significantly higher overall plaque frequency than those not taking them. The presence of classical cardiovascular risk factors was assessed according to the presence or absence of atheromatous plaque. Age was clearly related to the presence of subclinical atheromatosis. The mean age was 5.3 years older in the group with plaque than in the group without plaque (p < 0.001). Smoking was significantly related to the presence of subclinical atheromatosis, with plaque detected in 72.7 % of smokers and 50 % of non-smokers (p = 0.002). The mean packs smoked per year was more than double in patients with subclinical atheromatosis compared to those without plaque (11.89 vs. 5.88; p = 0.001). Dyslipidemia was shown to be a possible predictor of subclinical atheromatosis. Plaque was found in 70.7 % of patients with hypercholesterolemia vs. 56.5 % of the group without hypercholesterolemia (p = 0.052). However, no significant differences were observed between the means of total cholesterol, LDL-c, HDL-c and triglyceride values between patients with and without subclinical atheromatosis. The prevalence of cardiovascular risk factors specific to HIV infection was assessed according to the presence of subclinical atheromatosis. Patients with atheromatous plaque had on average 4.07 more years of exposure to HIV compared to the group without plaque (p = 0.001). The degree of immune activity and pro-inflammatory status as measured by CD4 and CD8 levels was related to the presence of atheroma plaque: a CD4/CD8 ratio < 0.7 was associated with subclinical atheromatosis (p = 0.003). The mean CD4 nadir was significantly lower in patients with atheroma plaque than in those without (p = 0.010) and the group with subclinical atheromatosis showed a worse immune profile, with a lower CD4 at diagnosis of HIV infection compared to the group without atherosclerotic plaque (p = 0.049). 100 % of patients with a CD4/CD8 ratio < 0.3 had subclinical atheromatosis (p = 0.001) and of the patients with CD4/CD8 > 1.7, none showed atheromatous plaque. Taking into account the joint and simultaneous influence of classical and specific plaquerelated risk factors, in response to the main study hypothesis, it was confirmed that HCV was significantly associated with the presence of subclinical atheromatosis (OR: 2.302; 95 % CI: 1.12-4.73; p = 0.023). After adjustment for all model variables, those that provided the most predictive information for the presence of subclinical atheromatosis were selected: age, smoking and CD4/CD8 < 0.7. The predictive ability of these three variables was analysed by multiple logistic regression analysis and led to a diagnostic yield of 75.3 % measured by the area under the ROC curve (95 % CI: 64- 80 %). In conclusion, the study demonstrates that HIV/HCV-coinfected patients without a previous cardiovascular event had significantly more subclinical atheromatosis compared to HIV-monoinfected patients (73.8 % vs. 55.9 %). CD4/CD8 ratio could be used as a marker of immune dysregulation and as an independent predictor of risk for subclinical atheromatosis, cardiovascular events and mortality.