A multivariate genetic analysis confirms rs5010528 in the human leucocyte antigen-C locus as a significant contributor to Stevens-Johnson syndrome/toxic epidermal necrolysis susceptibility in a Mozambique HIV population treated with nevirapine

J Antimicrob Chemother. 2018 Aug 1;73(8):2137-2140. doi: 10.1093/jac/dky180.


Objectives: Nevirapine is used in developing countries for the treatment of HIV infection, but its use is associated with rare serious adverse reactions such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Recently, an association between rs5010528 in the human leucocyte antigen (HLA)-C locus and SJS/TEN susceptibility has been described in sub-Saharan populations. Our aim was to verify this association in a population of nevirapine-treated patients from Mozambique.

Methods: The rs5010528 SNP was analysed by direct sequencing in 27 patients who had developed SJS/TEN and 75 patients who did not develop adverse reactions after nevirapine treatment. A case-control association study was conducted. A multivariate analysis was performed in order to evaluate the role of HLA-C also in relation to other susceptibility genetic factors (CYP2B6, TRAF3IP2, HCP5, PSORS1C1 and GSTM1 genes).

Results: rs5010528 was significantly associated with a higher risk of developing SJS/TEN; the variant allele was more frequent in cases than in controls, conferring a high risk of developing this adverse reaction in carriers (OR = 5.72 and P = 0.0002 at genotype level, OR = 3.51 and P = 0.0002 at allelic level). The multivariate analysis showed that the HLA-C SNP, CYP2B6 (rs28399499), TRAF3IP2 (rs76228616) and GSTM1 (null genotype) can explain 25% of the susceptibility to this reaction, with the HLA-C SNP as the most significant contributor (P = 0.02 and OR = 5.64).

Conclusions: Our study confirmed the association of the rs5010528 SNP in the HLA-C region with susceptibility to developing SJS/TEN in a population from Mozambique, suggesting that it could be a good genomic biomarker for SJS/TEN susceptibility in different sub-Saharan populations.

MeSH terms

  • Adult
  • Alleles
  • Anti-HIV Agents / adverse effects*
  • Anti-HIV Agents / therapeutic use
  • Case-Control Studies
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genotype
  • HIV Infections / drug therapy*
  • HLA-C Antigens / genetics*
  • Humans
  • Mozambique
  • Multivariate Analysis
  • Nevirapine / adverse effects*
  • Nevirapine / therapeutic use
  • Polymorphism, Single Nucleotide
  • Stevens-Johnson Syndrome / genetics*


  • Anti-HIV Agents
  • HLA-C Antigens
  • Nevirapine