We evaluated the predictive value of baseline HIV-1 genotypic resistance mutations for failure of a nucleoside reverse transcriptase inhibitor (NRTI) containing therapy. The change in therapy of 88 HIV-1-infected patients was analyzed retrospectively, relating the genotypic resistance profile at baseline to the evolution of vital load and CD4+ T cell counts. Genotypic resistance at baseline and at 6 months was evaluated with the LiPA HIV-1 RT, which detects mutations at codons 41, 69, 70, 74, 184, and 215. At 1 to 3 months after change in therapy, patients without preexisting resistance mutations to the new drug (group S) had a significantly better evolution in vital load (reduction of 0.37 log10) compared with patients with known preexisting resistance mutation(s) (group R) (increase of 0.08 log10). This difference was particularly striking for patients with the baseline M184V mutation and whose treatment was modified by the addition of lamivudine. After 6 months the median difference in vital load evolution between the two groups increased to 0.61 log10: the vital load of patients of group S was still 0.18 log10 below baseline while patients of group R had an increase of 0.43 log10 in vital load above baseline. Changes in CD4+ T cell counts were not significantly different. The evolution in vital load in HIV-1- infected patients with and without baseline resistance mutation(s) toward a newly added NRTI is significantly different at 1-3 months and at 6 months after changing or adding one NRTI.