A novel association of efavirenz induced severe cutaneous adverse reactions with HLA‐ DRB1*03:01: A case‐control study from North‐East India

HIV-infected patients have a higher risk of developing cutaneous reactions to drugs than the general population. Severe cutaneous adverse reactions (SCARs) are not uncommon in patients taking antiretroviral therapy (HAART]. To evaluate HLA class I and II allele frequencies in HIV patients on HAART who develop SCARs due to nevirapine (NVP] or efavirenz (EFZ] containing regime and compare this genotype composition with HAART tolerant patients and healthy organ donors. A case-control study for 4 years was conducted with four subsets of patients hailing from north-east India:Cohort 1- HIV seropositive patients who developed SCARs due to EFZ (n = 8];Cohort 2 - HIV seropositive patients who developed SCARs due to NVP (n = 15]; Cohort 3 -HIV seropositive NVP/EFZ-tolerant patients (n = 18]; Cohort 4 - Healthy HIV seronegative organ donors (n = 169].Cohort 3 & 4 acted as control-group. These patients were genotyped for the HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQB1, and HLA-DPB1 by a sequence-based HLA typing method. HLA-DRB1*03:01 allele revealed a significant association with EFZ regimen-induced SCARs in 62.5% patients compared with only 5.56% observed in HAART-tolerant patients and 4.14% in healthy organ. HLA-B*3505was found to be significantly associated with NVP induced SCARs. We found significant novel association of HLA-DRB1*03:01 with EFZ induced SCARs in North-East Indian HIV patients. Thus, HLA-DRB*03:01 may be useful as a genetic marker to avoid EFZ induced serious cutaneous rashes. The molecular HLA characterization of these alleles may provide a novel insight into the immunological basis of the antiretroviral drug reactions.