Avaliação de fatores clínicos, epidemiológicos e genéticos na reconstituição imune em pessoas vivendo com HIV

Abstract

HIV infection is primarily characterized by the persistent destruction of CD4 T cells, leading to AIDS progression and increased risk of morbidity and mortality. Genetic factors have been identified as modulators of the immune system, as dopamine plays a role in immunoregulation; thus, polymorphisms in dopamine receptors and the dopamine transporter may partly explain immune failure or recovery in individuals with HIV. Through the analysis of 417 medical records, the influence of clinical, epidemiological, and genetic factors on CD4 T cell counts was evaluated. In the association study, treatment duration was the only predictor of immune recovery (15 cells/µL/year). Individuals receiving the AZT/3TC/EFZ regimen showed an average annual reduction of 72 cells/µL in CD4 T cell counts compared to other regimens. Male participants had an average of 62 cells/µL fewer than females over the year. Advanced age at diagnosis negatively affected immune recovery, with an average reduction of 30 cells/µL per year. Initiating therapy with a CD4 T cell count < 200 cells/µL impaired recovery to > 500 cells/µL over seven years of treatment. Each log10 increase in viral load was associated with an average reduction of 61 cells/µL of CD4 T cells per year, and males had more difficulty achieving viral suppression than females (6.66 vs 6.34 copies/µL/log10) in the first year of therapy. This study is the first to evaluate the association between dopaminergic system polymorphisms and CD4 T cell recovery in people living with HIV; no significant association was observed for the polymorphisms DRD2: rs1800497, DRD3: rs6280, DRD4: rs1800955, and SLC6A3: rs27072 with immune recovery. We conclude that individuals with high viral load, male sex, advanced age at diagnosis, and treatment with AZT/3TC/EFZ are more likely to experience failure in CD4 T cell reconstitution.