0000000001168132
AUTHOR
Mc Re
Genotypic resistance profiles associated with virological failure to darunavir-containing regimens: a cross-sectional analysis.
Introduction: This study aimed at defining protease (PR) resistance mutations associated with darunavir (DRV) failure and PR resistance evolution at DRV failure in a large database of treatment-experienced human immunodeficiency virus (HIV) patients. Results: Overall, 1,104 patients were included: 118 (10.7%) failed at a median observation time of 16 months. The mean number of PR mutations at baseline was 2.7, but it was higher in patients who subsequently failed DRV. In addition, the number of PR mutations increased at failure. The increase in the mean number of mutations was completely related to mutations considered to be associated with DRV resistance following the indications of the ma…
Rules-based HIV-1 genotypic resistance interpretation systems predict 8 week and 24 week virological antiretroviral treatment outcome and benefit from drug potency weighting
Objectives: To test retrospectively the ability of four freely available rules-based expert systems to predict short- and medium-term virological outcome following an antiretroviral treatment switch in pre-treated HIV-1 patients. Methods: The HIV-1 genotype interpretation systems (GISs) HIVdb, ANRS, Rega and AntiRetroScan were tested for their accuracy in predicting response to highly active antiretroviral therapy using 8 week (n = 765) and 24 week (n = 634) follow-up standardized treatment change episodes extracted from the Italian Antiretroviral Resistance Cohort Analysis (ARCA) database. A genotypic sensitivity score (GSS) was derived for each genotype-treatment pair for the different GI…
A novel methodology for large-scale phylogeny partition
Understanding the determinants of virus transmission is a fundamental step for effective design of screening and intervention strategies to control viral epidemics. Phylogenetic analysis can be a valid approach for the identification of transmission chains, and very-large data sets can be analysed through parallel computation. Here we propose and validate a new methodology for the partition of large-scale phylogenies and the inference of transmission clusters. This approach, on the basis of a depth-first search algorithm, conjugates the evaluation of node reliability, tree topology and patristic distance analysis. The method has been applied to identify transmission clusters of a phylogeny …
Low Rate of Virological Failure and Maintenance of Susceptibility to HIV-1 Protease Inhibitors with First-Line Lopinavir/Ritonavir-Based Antiretroviral Treatment in Clinical Practice
Protease inhibitor (PI)-resistant HIV-1 has hardly ever been detected at failed boosted PI-based first-line antiretroviral regimens in clinical trials. However, this phenomenon has not been investigated in clinical practice. To address this gap, data from patients starting a first-line lopinavir/ritonavir (LPV/rtv)-based therapy with available baseline HIV-1 RNA load, a viral genotype and follow-up viral load after 3 and 6 months of treatment were extracted from the Italian Antiretroviral Resistance Cohort Analysis (ARCA) observational database. Based on survival analysis, 39 (7.1%) and 43 (7.8%) of the 548 examined patient cases had an HIV-1 RNA >500 and >50 copies/ml, respectively, after …
No pol mutation is associated independently with the lack of immune recovery in patients infected with HIV and failing antiretroviral therapy
An investigation was undertaken to determine whether specific pol mutations hinder long-term immune recovery regardless of virological response. In total, 826 patients with >50 HIV RNA copies/ml, who underwent genotypic resistance testing between 1 January 2000 and 31 December 2003 after >3 years of antiretroviral treatment, and were followed up for >3 years after genotypic resistance testing, were analyzed retrospectively. The outcome of the study was the lack of immune recovery after >3 years of follow-up, defined as a slope by linear regression 50 copies/ml divided by the number of HIV RNA measurements during follow-up. Logistic regression was used for univariable and multivariable analy…