Burden of Disease in PWH Harboring a Multidrug-Resistant Virus: Data From the PRESTIGIO Registry
Authors: Galli Laura , Parisi Maria Rita , Poli Andrea , Menozzi Marianna , Fiscon Marta , Garlassi Elisa , Francisci Daniela , Di Biagio Antonio , Sterrantino Gaetana , Fornabaio Chiara , Degli Antoni Anna , Angarano Gioacchino , Fusco Francesco Maria , D’Arminio Monforte Antonella , Corbelli Giulio Maria , Santoro Maria Mercedes , Zazzi Maurizio , Castagna Antonella ,   PRESTIGIO Study Group, Castagna Antonella , Gianotti Nicola , Galli Laura , Maggiolo Franco , Calza Leonardo , Focà Emanuele , Sterrantino Gaetana , Cenderello Giovanni , Di Biagio Antonio , Rusconi Stefano , Mussini Cristina , Menozzi Marianna , Antinori Andrea , Gagliardini Roberta , Bonora Stefano , Ferrara Micol , Zazzi Maurizio , Santoro Maria , Corbelli Giulio Maria , Zazzi Maurizio , Santoro Maria Mercedes , Galli Andrea , Carini Elisabetta , Parisi Maria Rita , Galli Laura , Poli Andrea , Bigoloni Alba , Tavio Marcello , Butini Luca , Giacometti Andrea , Vaccher Emanuela , Martellotta Ferdinando , Da Ros Valentina , Angarano Gioacchino , Saracino Annalisa , Balena Flavia , Maggiolo Franco , Comi Laura , Di Filippo Elisa , Valenti Daniela , Suardi Claudia , Mazzola Barbara , Viale Pierluigi , Calza Leonardo , del Turco Elena Rosselli , Ramirez Marta Vacas , Castelli Francesco , Focà Emanuele , Celotti Anna , Brognoli Francesca , Bonoldi Guido , Menzaghi Barbara , Abeli Clara , Farinazzo Maddalena , Ortu Francesco , Campus Marco , Cacopardo Bruno , Celesia Maurizio , Pan Angelo , Fornabaio Chiara , Bartoloni Alessandro , Sterrantino Gaetana , Rinaldi Francesca , Giachè Susanna , Pierluigi Blanc , Vichi Francesca , Fusco Francesco Maria , Santantonio Teresa , Ferrara Sergio , Bruno Serena Rita , Cassola Giovanni , Cenderello Giovanni , Marcello Feasi , Calautti Francesca , Bassetti Matteo , Di Biagio Antonio , Bruzzone Bianca , Artioli Stefania , Lazzarin Adriano , Castagna Antonella , Gianotti Nicola , Carini Elisabetta , Parisi Maria Rita , Galli Laura , Poli Andrea , Galli Andrea , Canetti Diana , Galli Massimo , Rusconi Stefano , Formenti Tiziana , Morena Valentina , Gabrieli Arianna , d’Arminio Monforte Antonella , Gazzola Lidia , Merlini Esther , Minieri Valentina , Gori Andrea , Bandera Alessandra , Pastore Valeria , Ferroni Valentina , Puoti Massimo , Moioli Cristina , Vassalli Sara , Mussini Cristina , Menozzi Marianna , Enrica Roncaglia , Giulia Nardini , Beghetto Barbara , Manzillo Elio , Franco Alfredo , Cattelan Anna Maria , Marinello Serena , Cavinato Silvia , Macario Annamaria , Cascio Antonio , Mazzola Giovanni , Antoni Anna Maria degli , Ferrari Carlo , Laccabue Diletta , Filice Gaetano , Gulminetti Roberto , Pagnucco Layla , Asti Annalia , Francisci Daniela , Schiaroli Elisabetta , Papalini Chiara , Italiani Francesca , Di Pietro Massimo , Magnani Giacomo , Elisa Garlassi , Barchi Enrico , Corsini Romina , Antinori Andrea , Gagliardini Roberta , Vergori Alessandra , Cicalini Stefania , Onnelli Giovanna , Giannetti Alberto , Cauda Roberto , Ciccullo Arturo , La Monica Silvia , Vullo Vincenzo , Dettorre Gabriella , Cavallari Eugenio Nelson , Andreoni Massimo , Malagnino Vincenzo , Ceccarelli Laura , Viviani Filippo , Sasset Lolita , Dentone Chiara , Rossetti Barbara , Modica Sara , Borgo Valentina , Di Perri Giovanni , Bonora Stefano , Ferrara Micol , Carcieri Chiara , Malena Marina , Fiscon Marta , Padovani Barbara , Luzzati Roberto , Centonze Sandro , Valentinotti Romina 
Published: September 2020

Background

Currently, no data are available on the burden of morbidity and mortality in people with HIV-1 (PWH) harboring a 4-class drug-resistant (4DR) virus (nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, integrase strand transfer inhibitors). The study aimed to assess the incidence of clinical events and death in this population.

Methods

This was a cohort study on PWH from the PRESTIGIO Registry with a documented 4DR virus. Burden of disease was defined as the occurrence of any new event including an AIDS-defining event (ADE) or non-AIDS-defining event (NADE) or death from any cause after 4DR evidence (baseline). Cox regression models evaluated factors associated with the risk of new clinical events/death.

Results

Among 148 PWH followed for a median (interquartile range) of 47 (32–84) months after 4DR evidence, 38 PWH had 62 new events or died from any cause (incidence rate, 9.12/100 person-years of follow-up; 95% CI = 6.85–11.39): 12 deaths (6 AIDS-related and 6 non-AIDS-related), 18 ADEs, 32 NADEs; 20 of the 38 NADEs (45%) of the incident clinical events were malignancies. The 4-year cumulative incidence of death was 6% (95% CI, 3%–13%), and that of ≥1 event or death was 22% (95% CI, 16%–31%). A higher risk of new clinical events/death was more likely in PWH with previous clinical events (adjusted hazard ratio [aHR], 2.67; 95% CI, 1.07–6.67) and marginally associated with lower baseline CD4+/CD8+ ratio (aHR, 0.82; 95% CI, 0.65–1.02).

Conclusions

PWH harboring 4DR have a high burden of disease with a worrying incidence of malignancies, strongly advising for close prevention and monitoring interventions as well as access to innovative therapeutic strategies, especially in people with a history of clinical events and low CD4+/CD8+ ratio.