Variability in the Interpretation of Transmitted Genotypic HIV-1 Drug Resistance and Prediction of Virological Outcomes of the Initial Haart by Distinct Systems
Authors:   the ICoNA drug resistance study group,   the ICoNA study group, Luca Andrea De , Cozzi-Lepri Alessandro , Perno Carlo-Federico , Balotta Claudia , Giambenedetto Simona Di , Poggio Antonio , Pagano Gabriella , Tositti Giulia , Piscopo Rita , Forno Antonio Del , Chiodo Francesco , Magnani Giacomo , Monforte Antonella d'Arminio , Angarano G , Antinori A , Balotta C , Cozzi-Lepri A , Monforte A d'Arminio , De Luca A , Monno L , Perno CF , Rusconi S , Montroni M , Scalise G , Zoli A , Del Prete MS , Tirelli U , Di Gennaro G , Pastore G , Ladisa N , Minafra G , Suter F , Arici C , Chiodo F , Colangeli V , Fiorini C , Coronado O , Carosi G , Cadeo GP , Castelli F , Minardi C , Vangi D , Rizzardini G , Migliorino G , Manconi PE , Piano P , Ferraro T , Scerbo A , Pizzigallo E , D'Alessandro M , Santoro D , Pusterla L , Carnevale G , Galloni D , Viganò P , Mena M , Ghinelli F , Sighinolfi L , Leoncini F , Mazzotta F , Pozzi M , Caputo S Lo , Angarano G , Grisorio B , Ferrara S , Grima P , Tundo P , Pagano G , Piersantelli N , Alessandrini A , Piscopo R , Toti M , Chigiotti S , Soscia F , Tacconi L , Orani A , Perini P , Scasso A , Vincenti A , Chiodera F , Castelli P , Scalzini A , Fibbia G , Moroni M , Lazzarin A , Cargnel A , Vigevani GM , Caggese L , d'Arminio Monforte A , Repetto D , Novati R , Galli A , Merli S , Pastecchia C , Moioli MC , Esposito R , Mussini C , Abrescia N , Chirianni A , Izzo C , Piazza M , De Marco M , Montesarchio V , Manzillo E , Graf M , Colomba A , Abbadessa V , Prestileo T , Mancuso S , Ferrari C , Pizzaferri P , Filice G , Minoli L , Bruno R , Novati S , Balzelli F , Loso K , Petrelli E , Cioppi A , Alberici F , Ruggieri A , Menichetti F , Martinelli C , De Stefano C , Gala A La , Ballardini G , Briganti E , Magnani G , Ursitti MA , Arlotti M , Ortolani P , Cauda R , Dianzani F , Ippolito G , Antinori A , Antonucci G , D'Elia S , Narciso P , Petrosillo N , Vullo V , De Luca A , Di Giambenedetto S , Zaccarelli M , Acinapura R , De Longis P , Ciardi M , D'Offizi G , Trotta MP , Noto P , Lichtner M , Capobianchi MR , Girardi E , Pezzotti P , Rezza G , Mura MS , Mannazzu M , Caramello P , Sinicco A , Soranzo ML , Gennero L , Sciandra M , Bonasso M , Grossi PA , Basilico C , Poggio A , Bottari G , Raise E , Pasquinucci S , De Lalla F , Tositti G , Resta F , Chimienti A , Lepri A Cozzi 
Published: April 2022

High level HIV-1 drug resistance in recently infected treatment-naive individuals correlates with sub-optimal virological responses to highly active antiretroviral therapy (HAART). To determine whether genotypic HIV-1 drug resistance in chronic naive patients, as interpreted by various systems, could predict the virological outcomes of HAART, isolates from patients enrolled in a prospective observational cohort (ICoNA) prior to treatment start were genotyped. Genotypic susceptibility scores (GSS) assigned to the initial HAART regimens using the interpretations of pre-therapy resistance mutations by 13 systems were related to virological outcomes. Of 415 patients, 42 (10%) had at least one major resistance mutation. According to the different interpretations, 1.9–20.5% of patients had some level of resistance to at least one drug in the initial regimen. In multivariable analysis, GSS from two systems significantly predicted the time to virological success: Rega 5.5, for each unit increase in GSS adjusted relative hazard (RH) 1.86 [95% confidence intervals (95% CI): 1.15–3.02] and hivresistanceWeb v3, RH 1.87 (95% CI: 1.00–3.48). With three other systems, GSS showed a trend towards a significant prediction of success: Retrogram 1.6, RH 2.33 (95% CI: 0.98–5.53), Menéndez 2002, RH 2.36 (95% CI: 0.97–5.72) and Stanford hivdb, RH 2.06 (95% CI: 0.94–4.49). Genotypic resistance testing coupled with adequate interpretation in chronic naive patients can usefully identify those at risk of sub-optimal virological response to HAART.