АСОЦІАЦІЇ АЛЕЛЕЙ HLA-DRB1 З РОЗВИТКОМ ВІЛ-ІНФЕКЦІЇ ТА КОМОРБІДНІСТЮ У ПАЦІЄНТІВ ЗІ СНІД

Abstract

The complicated situation with HIV in Ukraine requires an integrated approach to addressing the complex issues of managing.The aim of the study – to investigate association of HLA -DRB 1 alleles with development of HIV infection and comorbidity.Materials and Methods. The study included 70 patients with the fourth clinical stage of HIV infection who were followed on outpatient basis in the departments of the Dnipropetrovsk regional and municipal AIDS centers (Dnipro). Most of the patients were men – 41 (58.6 %). The age of the patients varied from 24 to 61 years and on average it was (38.91±0.87) years. The DRV 1 alleles were typed by the PCR method, variant of sequence-specific primers (PCR-SSP). The study was carried out by sets of "HLA-DNA -TEH" for the typing of DRB 1 genes produced by "DNA -Technology" (RU). Separately were analyzed: tuberculosis (n=26) and cerebral toxoplasmosis (n=23). Other diseases (HIV- encephalopathy, sepsis, generalized candidiasis, herpetic infection CMV chorioretinitis, HIV-cardiomyopathy) were grouped into group of others (n=21). The statistical processing of the research results was conducted using the STAT IST ICA v.6.1® application package.Results and Discussion. In patients with 4th clinical stage of HIV infection, majority of the alleles were DRB 1 * 01 (25.7 %), DRB 1 * 04 (20.0 %), DRB 1 * 07 (27.1 %), DRB 1 * 11 (38.6 %), DRB 1 * 13 (18.6 %), DRB 1 * 15 (18.6 %), DRB 1 * 16 (24.3 %). Alleles of DRB 1 * 02, DRB 1 * 05, DRB 1 * 06, DRB 1 * 09, DRB 1 * 06, DRB 1 * 09, DRB 1 * 18 genes were not detected. There were tendencies established for increase in patients with toxoplasmosis of carriers of alleles DRB 1* 01 (34.8%), DRB 1 * 15 (26.1 %), DRB 1 * 16 (34.8 %) than with other opportunistic diseases – 21.3 % (p=0.254 FET ), 14.9 % (p=0.330 FET) and 19.1 % (p=0.234 FET) respectively. The risk of developing toxoplasmosis among HIV-positive patients with DRB 1 * 13 alleles was significantly lower (p=0.012 FET), and DRB 1 * 16 gene allele carriers were higher than with tuberculosis (p=0.032 FET). A distinctive feature of tuberculosis was the higher frequency of carrier of alleles of DRB 1 * 13 gene (34.8 %) and DRB 1 * 08 (11.5 %) compared with other infections. The DRB 1 * 08 haplotype was detected only in patients with CNS tuberculosis. Lower risk of developing tuberculosis than other diseases (p=0.058) and  toxoplasmosis (p=0.032) was found in patients with DRB 1 * 16 haplotype. Lower levels of CD4 in the 4th clinical stage of HIV were associated with DRB 1 * 11, rs=-0.26; p <0.05, and decrease in the number of CD4 in the dynamics of observation - with DRB 1 * 17 (rs=-0.26; p<0.05). A higher level of HIV RNA was observed in the carriers of the DRB 1 * 04 allele (rs=+0.26; p<0.05). The progressive replication of the virus in the dynamics was associated with the presence of DRB 1 * 03 (rs=+0.42; p<0.001). In the analysis of the dependence of the terms from the definition of HIV status to the development of the 4th clinical stage of HIV, it was determined that patients with variants of the DRB 1 * 01 alleles (rs=+0.29; p<0.05), DRB 1 * 07 (rs=+0.27 ; p<0.05) have a slower development of HIV infection, which can be regarded as a kind of protective effect of these variants of haplotypes. On the contrary, carriers of DRB 1 * 15 alleles (rs=-0.28; p<0.05) were more prone to the rapid development of the disease.Conclusions. The typing of DRV 1 HLA Class II alleles is useful in predicting the development of HIV infection and comorbidity in HIV patients.