OBJECTIVE: To investigate the influence of genotypic resistance-guided HIV-treatment decisions on long-term clinical and virological outcomes in patients failing antiretroviral therapy by a prospective 30-month observation following a 6-month randomized study (Argenta trial). METHODS:Patients (n=174) with virological failure on highly active antiretroviral therapy (HAART) were initially randomized (1:1) to receive empirical therapy or guidance by genotypic resistance results. After month 6, all patients with HIV RNA >1,000 copies/ml received genotypic resistance tests and expert advice. Predictors of virological and clinical outcomes were analysed by logistic regression and Cox's regression models. RESULTS: There was a gradual increase in the proportion of patients with HIV RNA <400 copies/ml with 29.3% at 36 months (intent-to-treat) without differences between initial randomization arms. Independent predictors of 36-month virological response were the use of a salvage therapy with less daily doses and a more pronounced 3-month viral load drop. At 36 months, 84% survived without new AIDS events/death. Independent predictors of new AIDS events/death were previous AIDS events, higher baseline viral load, less pronounced 3-month viral load drop and, in a separate model, baseline protease substitutions K20M/R and 184V. CONCLUSIONS: The virological benefit of genotype-guided treatment decisions was continuously appreciable over time. Short-term virological response and viral cross-resistance were independent predictors of long-term outcomes.
RCT Entities:
OBJECTIVE: To investigate the influence of genotypic resistance-guided HIV-treatment decisions on long-term clinical and virological outcomes in patients failing antiretroviral therapy by a prospective 30-month observation following a 6-month randomized study (Argenta trial). METHODS:Patients (n=174) with virological failure on highly active antiretroviral therapy (HAART) were initially randomized (1:1) to receive empirical therapy or guidance by genotypic resistance results. After month 6, all patients with HIV RNA >1,000 copies/ml received genotypic resistance tests and expert advice. Predictors of virological and clinical outcomes were analysed by logistic regression and Cox's regression models. RESULTS: There was a gradual increase in the proportion of patients with HIV RNA <400 copies/ml with 29.3% at 36 months (intent-to-treat) without differences between initial randomization arms. Independent predictors of 36-month virological response were the use of a salvage therapy with less daily doses and a more pronounced 3-month viral load drop. At 36 months, 84% survived without new AIDS events/death. Independent predictors of new AIDS events/death were previous AIDS events, higher baseline viral load, less pronounced 3-month viral load drop and, in a separate model, baseline protease substitutions K20M/R and 184V. CONCLUSIONS: The virological benefit of genotype-guided treatment decisions was continuously appreciable over time. Short-term virological response and viral cross-resistance were independent predictors of long-term outcomes.
Authors: Mattia C F Prosperi; Michal Rosen-Zvi; André Altmann; Maurizio Zazzi; Simona Di Giambenedetto; Rolf Kaiser; Eugen Schülter; Daniel Struck; Peter Sloot; David A van de Vijver; Anne-Mieke Vandamme; Anders Sönnerborg Journal: PLoS One Date: 2010-10-29 Impact factor: 3.240
Authors: Andrea De Luca; Philippe Flandre; David Dunn; Maurizio Zazzi; Annemarie Wensing; Maria Mercedes Santoro; Huldrych F Günthard; Linda Wittkop; Theodoros Kordossis; Federico Garcia; Antonella Castagna; Alessandro Cozzi-Lepri; Duncan Churchill; Stéphane De Wit; Norbert H Brockmeyer; Arkaitz Imaz; Cristina Mussini; Niels Obel; Carlo Federico Perno; Bernardino Roca; Peter Reiss; Eugen Schülter; Carlo Torti; Ard van Sighem; Robert Zangerle; Diane Descamps Journal: J Antimicrob Chemother Date: 2016-01-28 Impact factor: 5.790