Respuesta inmune discordante en una cohorte de pacientes VIH en la provincia de Leóncaracterísticas clínicas y funcionales

Résumé

Objectives: to analyse a cohort of patients with discordant immune response (DIR) from a clinical and immunological perspective and compare them with another cohort of patients who, starting from a low nadir, achieve an adequate immune response. Patients and methods: this is a cross-sectional study that compares two cohorts of patients selected from the total number of patients with undetectable viral load under follow-up in the health service areas of El Bierzo and León. cohort 1 is made up of 16 patients with discordant immune response (<300 CD4/μL after at least 2 years of suppressed viral load). cohort 2 is made up of 17 patients with adequate immune response (patients starting from a low nadir, >500 CD4/μL after antiretroviral therapy (ART) and at least two years with suppressed viral load). The patients agreed to participate in the study and signed the Informed Consent approved by the Clinical Trials and Research Committee that governs both hospitals. Epidemiological and clinical data were obtained through clinical history and a personal interview with patients. Analytical data were obtained by determining laboratory parameters after taking blood samples from each participant. Results: the DIR rate in the studied population was 4,88%. No significant differences were found in the epidemiological or clinical variables between both cohorts, except for alcohol consumption in the past, higher in cohort 1 (p<0,001) and in the history of tuberculosis disease, higher in cohort 2 (p=0,047). There were also differences in the time that patients continuously received ART (p<0,001) and suppressed viral load, which was longer in cohort 2 (p<0,001). Under no circumstances ART was started early. All patients had adequate adherence in the two years prior to the study, however, eleven patients in cohort 1 and five in cohort 2 had presented adherence problems in the past. From an analytical point of view, significant differences were found in the absolute number of leukocytes (p<0,001), neutrophils (p=0,04), lymphocytes (p<0,001) and basophils (p<0,001), as well as in all the lymphocyte subpopulations analysed: total T (CD3+), CD4 T (CD3+CD4+), CD8 T (CD3+CD8+), NK (CD3-CD16/CD56+), total B lymphocytes (CD19+) and CD4/CD8 ratio. Regarding the analysis of memory and naïve lymphocytes, differences were found between both cohorts in absolute values, both in memory CD4 (p<0,001) and naïve CD4 (p<0,001), as well as memory CD8 (p<0,001) and naïve CD8 (p=0,03). In relation to the activation of T lymphocytes, a greater activation of CD4s (CD4+/CD69+/DR+ and CD4DR+CD25+) was detected, but not in the case of CD8s. Regarding the functional analysis of CD4+ T lymphocytes, no significant differences were observed in Th1, Th2, Th17 or Th22, but there were in the population of regulatory CD4 T lymphocytes (Treg), higher in cohort 1 (p=0,007). There were also no differences in the function of the thymus assessed according to the presence of RTE in peripheral blood. Regarding NK cells, significantly less cytotoxicity was detected in the group of discordant patients, even after increasing the proportion of NK cells and adding IL-2 (p=0,001). Regarding the function of neutrophils and monocytes, a greater phagocytic capacity was observed in monocyte phagocytosis in cohort 1 (p=0,02) but not in neutrophils. Conclusions: the DIR in this study was lower than the previously published in other studies, although their criteria are variable. Previous alcohol consumption was higher in DIR patients. This fact is possibly due to the size of the sample and the time of follow-up, no differences were demonstrated in the incidence of events related or not to AIDS or mortality. Time of suppressed viral load was a determining factor for immune recovery, since the patients with adequate immune response remained with suppressed viral load for more years. Lower absolute neutrophil and basophil values were observed in patients with DIR, as well as in all lymphocyte subpopulations (B lymphocytes, CD8+, NK cells) compared to patients with adequate immune response. Functional immunological factors: at a functional level, discordant patients presented greater activation of CD4+ lymphocytes and a decrease in naïve CD4+ lymphocytes, without differences in the recent thymic emigrants (RTE) values. NK cytotoxicity was significantly decreased in the cohort of patients with DIR, and improved after IL-2 administration, but remaining in lower ranges than those reached by patients with adequate immune recovery. The intensity of phagocytosis was higher in monocytes from patients with discordant immune response.