Factores de riesgo asociados al desarrollo de deterioro cognitivo en la pacientes VIH

Abstract

Objectives: To determine the prevalence of cognitive impairment in patients with HIV infection. To evaluate the risk factors associated with cognitive alterations in infected patients. To determine the discriminative capacity of the MoCA test (The Montreal Cognitive Assessment) to detect cognitive dysfunction in patients receiving stable antiretroviral treatment (ART). To assess which antiretroviral treatment is associated with a better cognitive performance. To analyze the existence of cellular immunoactivation in patients with HIV infection and its association with the presence of HAND. Methodology: Cross-sectional and observational study that includes 126 HIV patients receiving stable ART (for at least 6 months and with undetectable viral load). The patients underwent the MoCA screening test and a complete neuropsychological study, which evaluated 7 cognitive domains (attention, information processing speed, memory/learning, executive functions and abstraction, verbal fluency, motor skills and visuo-constructive skills). The presence of HAND was determined following the Frascati criteria. Three groups were distinguished: asymptomatic cognitive impairment (ANI), mild cognitive impairment (MND), and HIV-associated dementia (HAD). Blood samples were drawn following a wash/lysis protocol with activation/senescence marker detectors. To evaluate the association between qualitative and quantitative variables the Student T test was used, or the Mann-Whitney U test if the distribution was not normal. In order to evaluate the association between the qualitative variables, the Chi square test was used. It was considered significant if p was inferior to 0.05. Binary logistic regression analysis was performed to determine the associated factors. The area under the curve (AUC) was used to establish the discriminative ability of the MoCA test. The data collection was carried out in the data collection notebook and they were processed with the statistical package SPSS v.24. The study was approved by the Ethics Committee. All patients signed the informed consent. Results: The presence of HAND was detected in 91 patients (72,2%). 76 (60,3%9 were classified as ANI, 15 (11,9%) as MND and there were no patients with ADH. Compared to patients without HAND, patients with HAND were older, 48,69 (9,18) vs 42,43 (9,94) years, p<0,001, more likely to be foreigners (19,8 % vs 2,9%, p=0,036), had a lower educational level (15,6% vs 0% p<0,001), greater depression (51,1% vs 25,7%, p=0,018), lower intellectual activity (33,3% vs 14,3%, p<0,001), were more likely to perform less physical activity (48,9% vs 28,6%, p=0,067), had increased carotid intima-media thickness (0,69 (0.1) vs. 0,63 (0.13), p=0,086), with a higher probability of having subclinical atherosclerosis (48,8% vs. 28,6%, p=0,066) and a lower CD4 nadir 249,11 (182,03) vs 318,47 (184,35) cells/ml (p=0,068). The variables that were independently associated with and protective of HAND were being born in Spain (OR 0,072 (CI95% 0,008-0,648), p=0,019 and receiving treatment with NNRTIs (OR 0,2 (CI95% 0,06-0,66), p=0,009. Age was independently associated with the development of HAND (OR 1,075 (CI95% 1,017-1,137), p=0,011, as it was having a lower educational level (OR 7,12 (CI95% 2,2-23,043) p=0,001 and having depression (OR 6,21 (CI95% 1,8-21,2), p=0,004. Regarding the evaluation of the MoCA test, the average score was lower in patients with HAND than in patients without HAND (p <0,001), and a higher number of patients with HAND obtained a score of <26 (p <0,001). According to the results of the area under the curve (AUC), we obtained that the MoCA has a discriminative capacity for cognitive dysfunction HIV-associated of 81,9% (CI95% 0,737-0,901), p<0.001 The coordinates obtained from the ROC curve showed that the sensitivity of MoCA is 97% with a specificity of 35% for the cut point of 23. The positive predictive value (PPV) of the test was 87,83%, and the negative predictive value (NPV) was 50%. In the analysis of immunoactivation markers, patients with HAND had a higher percentage of HLA-DR in CD4+ T lymphocytes over the total lymphocytes, 8,01 (5,34-12,84) vs 10,85 (8,12-16,97), p=0,023, a more elevated percentage of HLA-DR in CD8+ T lymphocytes over the total lymphocytes, 14,54 (9,54-19,83) vs 20,19 (14,46-27,7), p=0,018, a higher number of the CD86+ marker in CD8+ T lymphocytes in absolute figures 7,4 (5,4-11,78) vs 15,29 (7,59-31,99), p=0,006, and a more elevated number of CD8+DR+ lymphocytes in absolute figures, 87,78 (61,38-139,38) vs. 156,72 (88,54-242,74), p=0,002 than patients without HAND. The marker that was independently associated with HAND in the multivariate analysis was HLADR+ in the absolute figure of CD8+ T lymphocytes, OR = 1,008 (CI95% 1,001-1,016), p=0,033.