Associations between human leukocyte antigen polymorphisms and hypersensitivity to antiretroviral therapy in patients with human immunodeficiency virus: A meta-analysis

Abstract

Background: Human leukocyte antigen (HLA) alleles are implicated in drug-induced hypersensitivity, including by nevirapine and abacavir. The purpose of this meta-analysis was to evaluate the relationship between HLA polymorphisms and hypersensitivity to antiretroviral therapy in human immunodeficiency virus (HIV)-infected patients. Methods: We conducted a systematic search of PubMed, Embase, Web of Science, and the Cochrane Library for studies that evaluated the associations of HLA polymorphisms with antiretroviral therapy-induced hypersensitivity published in April 2019. The summary odds ratios (ORs) with 95% confidence intervals (CIs) were considered as estimates of the effect. Results: The meta-analysis included 17 studies that assessed a total of 4273 patients. First, carriers of HLA-A*24 were associated with an increased risk of hypersensitivity among patients with HIV who received antiretroviral therapy (OR: 12.12; P = 0.018). Second, five SNPs of HLA-B genotypes, including*18 (OR: 1.63; P = 0.028),*35 (OR: 2.31; P = 0.002),*39 (OR: 11.85; P = 0.040),*51 (OR: 1.66; P = 0.028), and*81 (OR: 8.11; P = 0.021), were associated with an increased risk of hypersensitivity. Conversely, carriers of HLA-B*15 were associated with a reduced risk of hypersensitivity (OR: 0.43; P < 0.001). Third, HLA-C*04 was associated with an increased risk of hypersensitivity (OR: 3.09; P < 0.001), whereas a lower risk for hypersensitivity was observed in patients who were carriers of HLA-C*02 (OR: 0.22; P = 0.030),*03 (OR: 0.53; P = 0.049), and*07 (OR: 0.61; P = 0.044). Finally, carriers of HLA-DRB1*05 (OR: 0.18; P = 0.006) and*15 (OR: 0.23; P = 0.013) were associated with a reduced risk of hypersensitivity among patients receiving antiretroviral therapy. Conclusions: The findings of this meta-analysis indicated patients carrying HLA-A*24, HLA-B*18,*35,*39,*51,*81, HLA-C*04 were associated with a higher risk of hypersensitivity. Conversely, subjects carrying HLA-B*15, HLA-C*02,*03,*07, HLA-DRB1*05,*15 were associated with a reduced risk of hypersensitivity.