MHC class I and II genes dependent hypersensitivity to nevirapine and efavirenz in Indian HIV-1 patients

Abstract

Abstract OBJECTIVE The present study demonstrates and investigates the involvement of differences in human leukocyte antigens (HLA) class I and class II genes in the risk of hypersensitive reaction to nevirapine and efavirenz among Indian HIV- 1 infected patients. METHODS Thirty-three HIV-positive patients treated with efavirenz and nevirapine were studied. The HLA class I and II molecular typing in both Non-tolerant and tolerant patients were performed using the sequence-specific primers (SSP), the Olerup HLA-A-B-C and DQ-DR SSP Combi Tray. Odds ratios (OR) with 95 % confidence intervals (CI) were calculated to assess patients’ increased risk of developing hypersensitivity in comparison with Tolerant. RESULTS Thirteen patients (39.39%), developed a hypersensitive reaction thus requiring the drug to be discontinued. AnHLA-B*40 and HLA-C*15 allelesrevealed a significant association in 8/13 (61.53%) p = 0.028, OR= 9.6; 95% CI=1.04–222.49 and 7/13 (53.84%)p = 0.05, odds ratio (OR)= 8.75; 95% CI= 0.92–205.44 of hypersensitivity reaction in HIV patients compared with only 4% in Tolerant group, respectively. MHC class I genes, HLA-A*24 allele and MHC class II genes, DRB1*10:01:01:01 allele showed significant association with skin rash in 5/13 (38.46%) and 4/13 (30.76%) respectively (p<0.05). One patient developed potentially life-threatening condition i.e. Steven Johnson Syndrome. CONCLUSION A strong significant associations were seen between the MHC genes alleles (HLA-B*40 and HLA-C*15) and cART drug (nevirapine and efavirenz) induced skin rash in the Indian population. It can be utilized to avoid a subset of hypersensitivity reaction in HIV infected patients in Indian population.