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hrsa

participating institutions:
Johns Hopkins University AIDS Service, New York State DOH AIDS Institute, The CORE Center, Cook County Hospital



NEWS AND NEW DEVELOPMENTS



Genes and HIV reviewed

Individualizing HIV Treatment-Pharmacogenetics and Immunogenetics [Telente A et al. Lancet 2002;359:722]: This is an editorial concerning the report summarized above showing that the genetic susceptibility to abacavir hypersensitivity is regulated by the MHC 57·1 ancestral haplotype HLA-B*5701, DR7 and DQ3. The author notes that several genes influence HIV in terms of susceptibility to infection, natural history, response to treatment and, based on this report, tolerance to antiretroviral agents. These associations are summarized in the following table:

 
     

Gene

 Protein Function
 Influence
Susceptibility    
CCR5 Chemokine receptor Decreased Susceptibility
RANTES Chemokine Decreased Susceptibility
     
Natural history - progression    
CCR5 Chemokine receptor Delayed progression
CCR2 Chemokine receptor Delayed progression
MIP-1a Chemokine Accelerated progression
IL-10 Cytokine Accelerated progression
     
Class 1 HLA    
HLA-B*5701 MHC Delayed progression
HLA-B 35 MHC Accelerated progression
HLA-Cw04 MHC Accelerated progression
     
Treatment response    
CCR5 Chemokine receptor Viral response
MDR-1 Drug transport Drug levels
CYP2D6 CYP 450 1S0 enzyme Drug levels
     
Treatment toxicity    
SREBP-1C Lipid regulator Hyperlipidemia
HLA-B*5701
DR7, DQ3 		MHC ABC hypersensitivity

Comment: It has been theorized, mostly by infectious disease specialists, that the recent trends in medical discovery seem to emphasize that nearly all disease is caused by infection, genetics or bad luck. This report emphasizes the interface between infectious disease and heredity. The authors speculate that gene analysis may prove useful in treatment strategies in terms of determining the need to treat, the anticipated response to therapy and prediction of drug toxicities of not only abacavir, but other drugs as well.





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