NNRTI-Resistance Mutations and Response to New NNRTI-Containing Regimens
Three fundamental types of correlations form the basis of drug resistance knowledge: (i) Correlations between genotypic data with the treatments of persons from whom sequenced HIV-1 isolates have been obtained (genotype-treatment); (ii) Correlations between genotype and in vitro drug susceptibility (genotype-phenotype); and (iii) Correlations between genotype and the clinical response to a new treatment regimen (genotype-outcome). The following table summarizes the results of published studies linking RT genotype and the clinical response to a new NNRTI-containing regimen.
Nearly all publications on genotype and clinical outcome have described only the results of their analyses. None have published their underlying data, in part, because until now there had been no resource for making such data publicly available. As this database has now been modified to represent such data we have written to the authors of those studies that are most relevant today to request such data.
| Reference | Previous NNRTI | Follow-up NNRTI | Other Rx | No.Pts | Wk | Effect of Baseline Mutations on Response |
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| Madruga_(2007), Katlama_(2007), Lazzarin_(2007) DUET | 93% had received >= 1 NNRTI. All had >=1 NNRTI resistance mutation at screening or from a historical genotype | ETR vs placebo | DRV/RTV + OB | 406 | 24 | 13 baseline mutations were associated with a decreased response to ETR: V90I, A98G, L100I, K101EP, V106I, V179DF, Y181CIV, G190AS. When 3 or more of these mutations were present, the response to ETR was no different from placebo. |
Vingerhoets (2008)
DUET follow-up study | Additional 3 baseline mutations were identified as associated with a decreased VR (defined by RNA <50 copies/ml) at W24: K101H, E138A and V179T. 77% of patients with none of these 16 (13 from the study above + 3 new ones), 61% patients with one of these 16, 56% with two and 38% with >=3 were associated with a decreased VR. |
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