A simple screening approach to reduce B*5701-associated abacavir hypersensitivity on the basis of sequence variation in HIV reverse transcriptase

Clin Infect Dis. 2007 Jun 1;44(11):1503-8. doi: 10.1086/517499. Epub 2007 Apr 18.


Background: Abacavir hypersensitivity is strongly associated with the human leukocyte antigen (HLA)-B*5701 allele; however, the cost of routine high-resolution HLA typing before initiation of therapy remains prohibitive. We propose a simple approach to reduce B*5701-associated abacavir hypersensitivity based on the screening of human immunodeficiency virus (HIV) reverse transcriptase (RT) for a signature B*5701-associated cytotoxic T lymphocyte escape mutation at RT codon 245.

Methods: The correlation between HLA-B*5701 and RT codon 245 variation was investigated in 392 HIV-infected, antiretroviral-naive adults who were initiating highly active antiretroviral therapy. The relationship between codon 245 variation and premature abacavir discontinuation was investigated in a larger cohort of treated individuals (n=982). Associations between HLA-B*5701 and codon 245 variants were determined using Fisher's exact test or the chi (2) test.

Results: A very strong association between HLA-B*5701 and RT codon 245 variation was observed. Only 1 (4.2%) of 24 subjects with B*5701 harbored virus with the clade B "wild-type" amino acid 245V, compared with 278 (75.5%) of 368 who did not have B*5701 (P<.001). The sensitivity and specificity of codon 245 substitutions for predicting HLA-B*5701 were 96% and 75%, respectively, and the positive and negative predictive values were 20% and 99.6%, respectively. This association remained robust even after antiretroviral treatment was administered (negative predictive value, 100%; n=269). In abacavir-treated individuals (n=982), codon 245 substitutions were predictive of premature abacavir discontinuation (P=.02).

Conclusions: As HIV RT sequence is incidentally obtained as a part of routine drug-resistance testing, the examination of sequence variation at RT codon 245 could be adopted as a simple, low-cost screening method to identify individuals who could be safely treated with abacavir and/or who could benefit from HLA characterization.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Anti-HIV Agents / adverse effects*
  • Antiretroviral Therapy, Highly Active / adverse effects
  • Contraindications
  • Dideoxynucleosides / adverse effects*
  • Drug Hypersensitivity / genetics*
  • Female
  • Genetic Testing / economics
  • Genetic Testing / methods*
  • Genotype
  • HIV Reverse Transcriptase / antagonists & inhibitors
  • HIV Reverse Transcriptase / chemistry
  • HIV Reverse Transcriptase / genetics*
  • HLA-B Antigens / genetics*
  • Humans
  • Male
  • Mutation
  • Prevalence
  • Reverse Transcriptase Inhibitors / adverse effects*
  • Sensitivity and Specificity
  • Sequence Analysis, RNA


  • Anti-HIV Agents
  • Dideoxynucleosides
  • HLA-B Antigens
  • HLA-B*57:01 antigen
  • Reverse Transcriptase Inhibitors
  • HIV Reverse Transcriptase
  • abacavir