Baseline HIV Type 1 Genotypic Resistance to a Newly Added Nucleoside Analog Is Predictive of Virologic Failure of the New Therapy

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 viral 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 viral load (reduction of 0.37 log₁₀) compared with patients with known preexisting resistance mutation(s) (group R) (increase of 0.08 log_{1 0}). 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 viral load evolution between the two groups increased to 0.61 log_{1 0}: the viral load of patients of group S was still 0.18 log₁₀ below baseline while patients of group R had an increase of 0.43 log_{1 0} in viral load above baseline. Changes in CD4⁺ T cell counts were not significantly different. The evolution in viral 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.