An additive/substractive genotypic score as a determinant of the virological response to didanosine in HIV-1 infected patients

Objective: To assess the genotypic determinants of the virological response (VR) to didanosine (ddl) in nucleoside reverse transcriptase inhibitors (NRTI)-experienced patients. Methods: Human immunodeficiency virus type 1 (HIV-1) genotype was determined at baseline in 74 ddI-naive-patients with baseline viral load >500 copies/ml and receiving ddl as part of a new regimen. VR was defined as a plasma HIV-1 RNA <50 copies/ml after three months on ddl. NRTI resistance mutations associated with higher or lower frequencies of VR with a p-value < 0.25 were retained in different sets of mutations, where the mutations associated with a worse VR were added, whereas the mutations associated with a better VR were substracted. The most significant mutation scores were then studied in a multivariate analysis. Results: Changes at three codons (M41L L210W, T215Y/F/D/C/E) were associated with a worse VR and three mutations (K70R, M184V, K219Q) with a better VR. The strongest association with the VR was obtained with the score M41L + L210W + T215Y/F/D/C/E - K70R - K219Q. The score was independently associated with the VR in the multivariate analysis. Conclusion: Taking into account the mutations associated with a better VR may improve genotypic resistance algorithms. Our results are of interest for the management of antiretroviral therapy in NRTI -experienced patients. (C) 2006 Elsevier B.V. All rights reserved.