Minimal Emergence of Darunavir Resistance at Treatment Failure: Are Interpretation Algorithms Adequate? Gaetana Sterrantino* 1, Mauro Zaccarelli 2, Maurizio.

Presentazione sul tema: "Minimal Emergence of Darunavir Resistance at Treatment Failure: Are Interpretation Algorithms Adequate? Gaetana Sterrantino* 1, Mauro Zaccarelli 2, Maurizio."— Transcript della presentazione:

1 Minimal Emergence of Darunavir Resistance at Treatment Failure: Are Interpretation Algorithms Adequate? Gaetana Sterrantino* 1, Mauro Zaccarelli 2, Maurizio Zazzi 3, Andrea De Luca 4, Vanni Borghi 5, Paola Meraviglia 6, Paola Corsi 1, Stefano Bonora 7, Grazia Colao 8, Fausto Baldanti 9, Simona Di Giambenedetto 10, Tiziana Carli 11, Franco Maggiolo 12, Andrea Antinori 2, Francesco Leoncini 1 1 Malattie Infettive, Azienda Ospedaliera Universitaria Careggi, Firenze, Italy, 2 Istituto Nazionale per le Malattie Infettive “Lazzaro Spallanzani”, Roma, Italy, 3 Università di Siena, Dipartimento di Biologia Molecolare, Siena, for the ARCA database study group, Italy, 4 Istituto di Clinica Malattie Infettive, Roma, Italy, 5 Clinica Malattie Infettive, Modena, Italy, 6 Seconda Divisione Malattie Infettive Ospedale L. Sacco, Milano, Italy,7 Malattie Infettive Amedeo di Savoia, Torino, Italy, 8 Virologia Careggi, Firenze, Italy, 9 Virologia S. Matteo, Pavia, Italy,10 Clinica delle Malattie Infettive, Università Cattolica del Sacro Cuore di Roma, Roma, Italy,11 Malattie Infettive, Grosseto, Italy,12 Malattie Infettive, Bergamo, Italy. Background - Due to the high genetic barrier of Ritonavir-boosted Darunavir (DRV), resistance to this drug is associated with multiple mutational profiles. -We used a large database of HIV patients who were treated with a DRV-containing regimen to investigate protease (PR) evolution under DRV therapy at failure. Methods - Data were collected from patients included in the Italian ARCA database with a genotypic resistance test (GRT) done within 3 months before DRV start. - The protease mutations used to assess drv resistance were selected taking into account IAS-USA criteria. - The interppretation of drv resistance was analysed with HIV-DB, Rega and ARNS interpretation algorithms. Results A total of 840 DRV-treated patients were included: -759 (89%) patients had still undetectable viral load after a median of 54 weeks (IQR 23-112) of a DRV-containing regimen -81 (9.5%) experienced virological failure (median 43 weeks, IQR 18-62) with a DRV-containing regimen PI mutations at baseline in patients with virological success vs. patients failing DRV Baseline vs. follow-up PI mutationsin patients failing DRV 18/81 patients (22.2%) did not show any PI resistance mutation at baseline -15/81 (18.5%) did not show any PI resistance mutation also at failure Mean PI mutations of failing patients: baseline vs. follow-up Mean baseline PI mutations: 3.2 (±2.0) Mean follow-up PI mutations: 3.6 (±2.2) Mean PI mutations at baseline: successfull vs. failing patients p=0.0018 Proportions of patients with full resistance to DRV by interpretation algorithm (baseline vs. failure) Mean PI mutations in patients with virological success: 2.5 (±1.9) Mean PI mutations in patients with treatment failure: 3.2 ((±2.0) p=NS Conclusions - In this cohort analysis, protease mutations associated with reduced virological response to Darunavir were in agreement with currently used algorithms. - However, susceptibility to DRV was generally maintained even in the presence of virological failure of regimens containing the drug. - Although there is not complete agreement between different algorithms tested, for the Stanford interpretation algorithm, full resistance to DRV is uncommon, so that most patients retained partial or complete DRV susceptibility with several patients lacking any protease mutation.