Polypharmacy, anticholinergic burden and drug–drug interaction assessment in people with four-class-resistant HIV: data from the PRESTIGIO registry
Authors: Mazzitelli Maria , Pontillo Domenico , Clemente Tommaso , Di Biagio Antonio , Cenderello Giovanni , Rusconi Stefano , Menzaghi Barbara , Fornabaio Chiara , Garlassi Elisa , Zazzi Maurizio , Castagna Antonella , Cattelan Anna Maria ,   PRESTIGIO Study Group, Castagna Antonella , Spagnuolo Vincenzo , Galli Laura , Maggiolo Franco , Calza Leonardo , Focà Emanuele , Lagi Filippo , Cenderello Giovanni , Di Biagio Antonio , Marchetti Giulia , Rusconi Stefano , Cervo Adriana , Gagliardini Roberta , Bonora Stefano , Cattelan Anna Maria , Zazzi Maurizio , Santoro Maria Mercedes , Zazzi Maurizio , Santoro Maria Mercedes , Galli Andrea , Saladini Francesco , Armenia Daniele , Carini Elisabetta , Bagaglio Sabrina , Galli Laura , Lolatto Riccardo , Diotallevi Sara , Tavio Marcello , Paggi Alessandra Mataloni , Ripoli Bagno A , Vichi Francesca , Bellucci Alessio , Mirabelli Elisa , Saracino Annalisa , Balena Flavia , Maggiolo Franco , Comi Laura , Valenti Daniela , Suardi Claudia , Calza Leonardo , Malerba Federica , Castelli Francesco , Focà Emanuele , Minisci Davide , Pennati Francesca , Celotti Anna , Brognoli Francesca , Menzaghi Barbara , Farinazzo Maddalena , Cacopardo Bruno , Celesia Benedetto Maurizio , Raddusa Michele Salvatore Paternò , Giarratana Carmen , Torti Carlo , Fusco Paolo , Bruno Gabriele , Pan Angelo , Brambilla Paola , Fornabaio Chiara , Bartoloni Alessandro , Giachè Susanna , Corsi Paola , Kiros Seble Tekle , Lagi Filippo , Ducci Filippo , Santantonio Teresa , Caputo Sergio Lo , Ferrara Sergio , Narducci Marianna , Pontali Emanuele , Feasi Marcello , Sarà Antonio , Bassetti Matteo , Di Biagio Antonio , Blanchi Sabrina , Castagna Antonella , Spagnuolo Vincenzo , Carini Elisabetta , Bagaglio Sabrina , Galli Laura , Lolatto Riccardo , Galli Andrea , Clemente Tommaso , Borjesson Rebecka Papaioannu , Diotallevi Sara , Antinori Spinello , Formenti Tiziana , Giacomelli Andrea , Marchetti Giulia , Gazzola Lidia , De Flaviis Federica , Puoti Massimo , Moioli Cristina , D’Amico Federico , Mussini Cristina , Cervo Adriana , Enrica Roncaglia , Giulia Nardini , Beghetto Barbara , Manzillo Elio , Lanzardo Amedeo , Cattelan Anna Maria , Mazzitelli Maria , Cascio Antonio , Trizzino Marcello , Fronti Elisa , Laccabue Diletta , Gulminetti Roberto , Zuccarini Andrea , Francisci Daniela , Schiaroli Elisabetta , De Socio Giuseppe , Garlassi Elisa , Corsini Romina , Gagliardini Roberta , Fusto Marisa , Sarmati Loredana , Malagnino Vincenzo , Lamonica Silvia , Di Giambenedetto Simona , Mulas Tiziana , Cenderello Giovanni , Pincino Rachele , Tumbarello Mario , Fabbiani Massimiliano , Panza Francesca , Rancan Ilaria , Di Perri Giovanni , Bonora Stefano , Ferrara Micol , Fantino Silvia , Malena Marina , Fiscon Marta 
Published: July 2024

Abstract

Objectives
To evaluate polypharmacy, anticholinergic burden (ACB) and drug–drug interactions (DDIs) in people with four-class-resistant HIV (4DR-PWH).

Methods
We performed a cross-sectional study, including 4DR-PWH from the PRESTIGIO Registry taking at least one non-antiretroviral drug. Polypharmacy was defined as taking five or more non-antiretroviral drugs. ACB was calculated using the ACB scale: 0 = no AC effect, 1–2 = low/moderate risk, ≥3 = high AC risk. Participants’ characteristics by ACB score were compared using the Kruskal–Wallis test, and Spearman's correlation coefficient was used to assess linear relationships. DDIs were evaluated using the Liverpool database.

Results
Overall, 172 4DR-PLWH were evaluated: 75.6% males, median age 49.9 years (IQR = 45.6–56), 62 (27.1%) on polypharmacy, 124 (72.1%) using a boosting agent and 72 (41.8%) with four or more antiretrovirals. Based on ACB, 128 (74.45%), 33 (19.2%) and 11 (6.4%) had a no, low/moderate and high AC risk, respectively. The most common AC drugs were β-blockers (12.2%), diuretics (8.7%) and antidepressants (8.7%). The high ACB was significantly related to the number of drugs/person (r = 0.33, P &lt; 0.0001) and the number of clinical events (r = 0.222, P = 0.004). Overall, 258 DDIs were found between antiretrovirals and co-medications in 115 (66.8%) PWH, and 14 (8.1%) PWH received contraindicated drug combinations.

Conclusions
In 4DR-PWH, polypharmacy, DDIs and the proportion of people with moderate/high AC burden were high. In 4DR-PWH undetectability achievement and maintenance is the priority and use of boosted PIs is common. A strict collaboration (infectious diseases specialists, virologists, pharmacologists) is needed to limit the risk of ACB and DDIs and to explore the advantages of new antiretrovirals.