To validate the clinical utility of the current TPV genotypic score and describe the role of additional protease mutations in determining the virological response to tipranavir/ritonavir, 176 pluri-experienced HIV-infected patients with a baseline genotypic profile were evaluated. Univariate and multivariate analyses, using a stepwise estimation model with backward procedure, were performed to identify variables associated with virological response to a new regimen including tipranavir after 12 and 24 weeks. Results relative to the subanalysis of data using the achievement of a viral load decrease of at least 1 log as primary endpoint are presented herein.
At week 24, 62.6% of patients had a ≥1 log HIV-RNA decrease. The following variables were significantly (p<0.05) associated with response in multivariate analysis: CD4 nadir, number of previous protease inhibitors and CDC stage C. TPV score was predictive of outcome with univariate, but not multivariate, analysis. Among mutations, Q58E (p=0.040) and Q92K (p=0.027) were associated with failure, while L76V (OR p=0.002) was associated with success. This study suggests that the current TPV-associated mutation list does not fully reflect the genotypic profile of TPV resistance in our clinical cohort, and the role of additional mutations needs to be considered. Of note, the L76V mutation appeared to have a beneficial impact on the virological response to TPV. Keywords: Tipranavir; Genotypic resistance; Antiretrovirals.
Articolo presente in – HAART and correlated pathologies n. 1 –