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P atients on PI may fail without key mutations in protease !

P atients on PI may fail without key mutations in protease ! Discordant resistance calls for Pr !  Complementing contributions in ga g (example I54V – ATV ?) How can Gag mutations contribute to PI resistance? CS mutations affect Gag processing

kenneth-garza
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P atients on PI may fail without key mutations in protease !

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  1. Patients on PI may fail without key mutations in protease! • Discordant resistance calls for Pr!  Complementing contributions in gag (example I54V – ATV?) How can Gag mutations contribute to PI resistance? • CS mutations affect Gag processing • Changed conformation (processing rate?) • 2ndary mutations can compensate / enhance effects • Can cause drug resistance by themselves Our Study: 870 HIV-1 subtype B genotypes (ViroSeq) from SHCS w/ treatment history, VL, CD4 3’ end of gag seq retrieved (≤600Nucleotides, focus on CS p1/p6) from hidden file information associate mutations and therapy / naïve state

  2. specific and position-precise Gag interaction with protease PR G48 + I47V associate with S451N R452S: polar contact with PR D30, Q58 lost

  3. Poster MoPDA 0101 Summary / outlook • Therapy associated Gag mutations are rare but not random (crucial positions near CS: eg. 8% vs 0.4%) • Mutations in Gag correlate strongly with PI-treatment • The most frequently found Gag-mutations alone do not cause full resistance • Gag mutations affect viral fitness • Strong links among certain new gag mutations identified (451/453: 4/7; 427/453: 4/4) • Phenotyping of triple mutant is ongoing • May help explain discordance in PI scores

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