HLA-dependent hypersensitivity to nevirapine in Sardinian HIV patients

Background: Hypersensitivity reaction to nevirapine, which in some cases can be fatal, shows a higher prevalence in Sardinia in comparison with other Italian regions. Objective: This study demonstrates that hypersensitive reaction to nevirapine in Sardinian HIV-infected patients is associated with the HLA CW8-B14 haplotype. These two HLA class I antigens are in strong linkage disequilibrium in the Sardinian population. Methods: Forty-nine Sardinian HIV-positive patients treated with nevirapine were studied. Thirteen (26%), developed a hypersensitive reaction thus requiring the drug to be discontinued. HLA class I and II molecular typing was performed in both nevirapine-hypersensitive and nevirapine-tolerant patients. To avoid biased representation of the allele frequencies in the two groups of treated patients, molecular typing was also performed in 82 HIV-positive patients who had not been treated with nevirapine. Results: Considerable overlap was observed for the clinical, immunological and demographic characteristics of the 13 hypersensitive patients and 36 tolerant patients. Clinical parameters included viral load, status of HIV infection, CD4 and CD8 cell counts, hepatitis C virus/hepatitis B virus co-infections. Forty-six percent (6/13) of the nevirapine-hypersensitive subjects had the HLA-Cw8 and HLA-B14(65) antigens compared with 5% (2/36) of the nevirapine-tolerant group (P = 0.004; P-c = 0.05). Conclusion: In agreement with other recent reports, the utility of HLA typing in HIV patients to identify genetic factors that may confer susceptibility to drug-induced hypersensitive reaction was confirmed. A careful choice of antiretroviral therapy in susceptible individuals should significantly reduce the risk of severe hypersensitive reaction