Association of HLA‐B*53 With DRESS Syndrome in Patients Treated With Raltegravir: Two Case Reports and a Literature Review

Introduction Raltegravir, an HIV integrase inhibitor, although generally well tolerated, may cause severe reactions such as drug reaction with eosinophilia and systemic symptoms (DRESS). This syndrome has been associated with impaired drug metabolism, viral reactivation and genetic factors including HLA‐B*53:01 . We describe two cases of DRESS in a raltegravir‐treated cohort and review the relevant literature. Methodology Medical records from Hospital Universitario de La Princesa (2008–2020) were retrospectively reviewed to identify patients genotyped for HLA‐B*53 who received raltegravir. Suspected DRESS cases were assessed using the RegiSCAR scoring system and Naranjo algorithm. A structured literature search was conducted to identify additional published cases. Results Among 109 patients treated with raltegravir, three (2.8%) were HLA‐B*53 carriers. Two developed DRESS, while no events occurred in non‐carriers. One presented with fever, rash, lymphadenopathy, hepatitis and HHV‐6 reactivation (RegiSCAR 6). The second developed eosinophilia, rash and pulmonary symptoms (RegiSCAR 4). The third carrier remained asymptomatic. A continuity correction yielded a RR of 133.9. Nine additional cases were identified in the literature and summarized according to clinical features and HLA‐B*53 status. Conclusion Findings support a potential genetic predisposition involving HLA‐B*53:01 in raltegravir‐induced DRESS. Screening in high‐prevalence populations may help prevent severe reactions. Further research should refine diagnostic and management strategies.