ABSTRACT: BACKGROUND:Tuberculosis (TB) and AIDS are the leading causes of infectious disease death worldwide. In some TB-HIV co-infected individuals treated for both diseases simultaneously, a pathological inflammatory reaction termed immune reconstitution inflammatory syndrome (IRIS) may occur. The risk factors for IRIS are not fully defined. We investigated the association of HLA-B, HLA-C, and KIR genotypes with TB, HIV-1 infection, and IRIS onset. METHODS:Patients were divided into four groups: Group 1- TB+/HIV+ (n?=?88; 11 of them with IRIS), Group 2- HIV+ (n?=?24), Group 3- TB+ (n?=?24) and Group 4- healthy volunteers (n?=?26). Patients were followed up at INI/FIOCRUZ and HGNI (Rio de Janeiro/Brazil) from 2006 to 2016. The HLA-B and HLA-C loci were typed using SBT, NGS, and KIR genes by PCR-SSP. Unconditional logistic regression models were performed for Protection/risk estimation. RESULTS:Among the individuals with TB as the outcome, KIR2DS2 was associated with increased risk for TB onset (aOR?=?2.39, P?=?0.04), whereas HLA-B*08 and female gender were associated with protection against TB onset (aOR?=?0.23, P?=?0.03, and aOR?=?0.33, P?=?0.01, respectively). Not carrying KIR2DL3 (aOR?=?0.18, P?=?0.03) and carrying HLA-C*07 (aOR?=?0.32, P?=?0.04) were associated with protection against TB onset among HIV-infected patients. An increased risk for IRIS onset was associated with having a CD8 count ?500 cells/mm3 (aOR?=?18.23, P?=?0.016); carrying the KIR2DS2 gene (aOR?=?27.22, P?=?0.032), the HLA-B*41 allele (aOR?=?68.84, P?=?0.033), the KIR2DS1?+?HLA-C2 pair (aOR?=?28.58, P?=?0.024); and not carrying the KIR2DL3?+?HLA-C1/C2 pair (aOR?=?43.04, P?=?0.034), and the KIR2DL1?+?HLA-C1/C2 pair (aOR?=?43.04, P?=?0.034), CONCLUSIONS: These results suggest the participation of these genes in the immunopathogenic mechanisms related to the conditions studied. This is the first study demonstrating an association of HLA-B*41, KIR2DS2, and KIR + HLA-C pairs with IRIS onset among TB-HIV co-infected individuals.
