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Host genes

Exposure variable. degree of polymorphism/ adaptation. HIV Gag↔other. Drugs / Xenobiotics. HCV. Host genes. degree of polymorphism. Drug metabolising enzymes/transporters. CD4. HLA. NKr/KIR. Mallal S, Clinical Opinions in HIV and AIDS 2006, 1:218-219. Immune deficiency. Rapid

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Host genes

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  1. Exposure variable degree of polymorphism/ adaptation HIV Gag↔other Drugs / Xenobiotics HCV Host genes degree of polymorphism Drug metabolising enzymes/transporters CD4 HLA NKr/KIR Mallal S, Clinical Opinions in HIV and AIDS 2006, 1:218-219

  2. Immune deficiency Rapid Slow Polymorphisms of the Host and Pathogen Interact at Multiple Levels Over Time CCR5Δ32 Rare HLA 8.1AH KIR 3DS1 HLA-B*5701 -B*2705 B8/KS B35/MAC Host Exposed population Viral load Specific AIDS Illnesses Established Infection High Low **Adaptation to HLA restricted responses Pathogen X4 Virus

  3. 3TC ad OR= bc Both Escape and Reversion Favor an Increase in the Odds Ratio Viral polymorphism WT M184V Replicative cost (0.2) 3TC on WT (1.5) No 3TC 5.0 4.8 0.2 3TC on escaped (0.1)  a Reversion b  Drug 1.2 3TC 3.5 4.7 Escape  d c 

  4. CTL Gag T242N associated with HLA-B*5701 has a a replicative cost evident at population level Viral polymorphism Gag T242N (Escaped) Gag T242T (WT) Replicative cost (0.6, p=0.02) Host polymorphism CTL on non- escaped (1.1, p=0.02) Non- B*5701 4.9 4.3 CTL on escaped a b B*5701 3.8 4.7 c d Mean viral load (log), n=197

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