Doravirine Plus Integrase Strand Transfer Inhibitors as a 2-Drug Treatment-Switch Strategy in People Living with HIV: The Real-Life DORINI Multicentric Cohort Study.
Journal
Journal of acquired immune deficiency syndromes (1999)
ISSN: 1944-7884
Titre abrégé: J Acquir Immune Defic Syndr
Pays: United States
ID NLM: 100892005
Informations de publication
Date de publication:
01 11 2023
01 11 2023
Historique:
received:
04
02
2023
accepted:
20
06
2023
medline:
23
10
2023
pubmed:
28
9
2023
entrez:
27
9
2023
Statut:
ppublish
Résumé
Few data are available about the efficacy, durability, and tolerability of doravirine (DOR) + integrase strand inhibitors (INI) as a switching strategy among antiretroviral therapy (ART)-experienced people living with HIV (PLWH). Retrospective, multicenter cohort study investigating the durability, efficacy, and tolerability of 2 off-label drug associations of DOR + INI among ART-experienced PLWH. The study included PLWH who switched to DOR combined with either raltegravir (RAL) or dolutegravir (DTG) between June 1, 2020, and December 31, 2021, with at least 1 follow-up (FU) visit. Virologic, biometric, and metabolic parameters were evaluated at baseline (T0) and at 1-3 (T1), 6 (T2), and 12 (T3) months. Univariate and multivariate survival analyses assessed the 28-week probability of persistence on the regimens. Patient satisfaction was measured using the HIV Treatment Satisfaction Questionnaire. Ninety-five PLWH were included, 52 in DOR + RAL and 43 in DOR + DTG. Six treatment discontinuations were reported during a mean of 37 (±17) weeks of FU (incidence of 2.7 × 1000 person-weeks FU). Only 2 were the result of virological failure without resistance mutations. DOR + DTG demonstrated significantly higher 28-week persistence than DOR + RAL (HR 1.90, 95% CI: 1.24-2.90, log-rank: P = 0.003). Weight, waist circumference, and fasting lipids reduced considerably at T3 vs T0. Overall, high satisfaction with the new treatment was reported, particularly in the DOR + RAL (68 (64-72)/72), compared with the DOR + DTG group (58 (50-65)/72, P < 0.001). Our experience revealed few treatment discontinuations, improved metabolic parameters, and high patient satisfaction among ART-experienced PLWH switching to DOR combined with INI, irrespective of the specific INI used.
Sections du résumé
BACKGROUND
Few data are available about the efficacy, durability, and tolerability of doravirine (DOR) + integrase strand inhibitors (INI) as a switching strategy among antiretroviral therapy (ART)-experienced people living with HIV (PLWH).
SETTING
Retrospective, multicenter cohort study investigating the durability, efficacy, and tolerability of 2 off-label drug associations of DOR + INI among ART-experienced PLWH.
METHODS
The study included PLWH who switched to DOR combined with either raltegravir (RAL) or dolutegravir (DTG) between June 1, 2020, and December 31, 2021, with at least 1 follow-up (FU) visit. Virologic, biometric, and metabolic parameters were evaluated at baseline (T0) and at 1-3 (T1), 6 (T2), and 12 (T3) months. Univariate and multivariate survival analyses assessed the 28-week probability of persistence on the regimens. Patient satisfaction was measured using the HIV Treatment Satisfaction Questionnaire.
RESULTS
Ninety-five PLWH were included, 52 in DOR + RAL and 43 in DOR + DTG. Six treatment discontinuations were reported during a mean of 37 (±17) weeks of FU (incidence of 2.7 × 1000 person-weeks FU). Only 2 were the result of virological failure without resistance mutations. DOR + DTG demonstrated significantly higher 28-week persistence than DOR + RAL (HR 1.90, 95% CI: 1.24-2.90, log-rank: P = 0.003). Weight, waist circumference, and fasting lipids reduced considerably at T3 vs T0. Overall, high satisfaction with the new treatment was reported, particularly in the DOR + RAL (68 (64-72)/72), compared with the DOR + DTG group (58 (50-65)/72, P < 0.001).
CONCLUSIONS
Our experience revealed few treatment discontinuations, improved metabolic parameters, and high patient satisfaction among ART-experienced PLWH switching to DOR combined with INI, irrespective of the specific INI used.
Identifiants
pubmed: 37757865
doi: 10.1097/QAI.0000000000003248
pii: 00126334-990000000-00266
doi:
Substances chimiques
HIV Integrase Inhibitors
0
doravirine
913P6LK81M
Raltegravir Potassium
43Y000U234
Anti-HIV Agents
0
Pyridones
0
Heterocyclic Compounds, 3-Ring
0
Integrases
EC 2.7.7.-
Types de publication
Multicenter Study
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
235-243Informations de copyright
Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.
Déclaration de conflit d'intérêts
The authors have no funding or conflicts of interest to disclose.
Références
Soriano V, Fernandez-Montero JV, Benitez-Gutierrez L, et al. Dual antiretroviral therapy for HIV infection. Expert Opin Drug Saf. 2017;16:923–932.
Prieto P, Podzamczer D. Switching strategies in the recent era of antiretroviral therapy. Expert Rev Clin Pharmacol. 2019;12:235–247.
Joly V, Burdet C, Landman R, et al. Dolutegravir and lamivudine maintenance therapy in HIV-1 virologically suppressed patients: results of the ANRS 167 trial (LAMIDOL). J Antimicrob Chemother. 2019;74:739–745.
Llibre JM, Hung CC, Brinson C, et al. Efficacy, safety, and tolerability of dolutegravir-rilpivirine for the maintenance of virological suppression in adults with HIV-1: phase 3, randomised, non-inferiority SWORD-1 and SWORD-2 studies. Lancet. 2018;391:839–849.
Baril JG, Angel JB, Gill MJ, et al. Dual therapy treatment strategies for the management of patients infected with HIV: a systematic review of current evidence in ARV-naive or ARV-experienced, virologically suppressed patients. PloS One. 2016;11:e0148231.
EACS Guidelines 2021. EACS; 2020 https://www.eacsociety.org/guidelines/eacs-guidelines/ . Accessed August 20, 2023.
Mazzitelli M, Degli Antoni M, Castelli F, et al. Real-life use of Doravirine in treatment-experienced people living with HIV: a multicenter Italian study. Medicine. 2022;101:e29855.
Soulie C, Santoro MM, Charpentier C, et al. The rare occurrence of doravirine resistance-associated mutations in HIV-1-infected treatment-naive patients. J Antimicrob Chemother. 2019;74:614–617.
Stockdale AJ, Khoo S. Doravirine: its role in HIV treatment. Curr Opin HIV AIDS. 2022;17:4–14.
Wang X, Milinkovic A, Pereira B, et al. Pharmacokinetics of once-daily doravirine over 72h following drug cessation. J Antimicrob Chemother. 2020;75:1658–1660.
Mazzitelli M, Sasset L, Leoni D, et al. Real-life use of dolutegravir doravirine dual regimen inexperienced elderly PLWH with multiple comorbidities and on polypharmacy: a retrospective analysis. Medicine. 2021;100:e28488.
HIV Drug Resistance Database. https://hivdb.stanford.edu/ . Accessed August 20, 2023.
Woodcock A, Bradley C. Validation of the HIV treatment satisfaction questionnaire (HIVTSQ). Qual Life Res Int J Qual Life aspects Treat Care Rehabil. 2001;10:517–531.
The jamovi project. 2022. jamovi . (Version 2.3). https://www.jamovi.org . Accessed August 20, 2023.
Kumar P, Johnson M, Molina JM, Rizzardini G. Brief report: switching to DOR/3TC/TDF maintains HIV-1 virologic suppression through week 144 in the DRIVE-SHIFT trial. J Acquir Immune Defic Syndr (1999). 2021 87, 801–805.
Ciccullo A, D'Angelillo A, Iannone V, et al. Real-life safety of doravirine in treatment-experienced, virologically suppressed PLWHIV. J Acquir Immune Defic Syndr (1999). 2021, 88, e5–e6.
Orkin C, Squires KE, Molina JM, et al. Doravirine/lamivudine/tenofovir disoproxil fumarate (TDF) versus efavirenz/emtricitabine/TDF in treatment-naive adults with human immunodeficiency virus type 1 infection: week 96 results of the randomized, double-blind, phase 3 DRIVE-AHEAD noninferiority trial. Clin Infect Dis official Publ Infect Dis Soc Am. 2021;73:33–42.
Molina JM, Squires K, Sax PE, et al. Doravirine versus ritonavir-boosted darunavir in antiretroviral-naive adults with HIV-1 (DRIVE-FORWARD): 96-week results of a randomised, double-blind, non-inferiority, phase 3 trial. Lancet HIV. 2020;7:e16–e26.
Rokx C, Schurink C, Boucher C, et al. Dolutegravir as maintenance monotherapy: first experiences in HIV-1 patients: Table 1. J Antimicrob Chemother. 2016;71:1632–1636.
Brenner B, Thomas R, Blanco JL, et al. Development of a G118R mutation in HIV-1 integrase following a switch to dolutegravir monotherapy leading to cross-resistance to integrase inhibitors. J Antimicrob Chemother. 2016;71:1948–1953.
Fournier AL, Hocqueloux L, Braun DL, et al. Dolutegravir monotherapy as maintenance strategy: a meta-analysis of individual participant data from randomized controlled trials. Open Forum Infect Dis. 2022;9:6.
Efficacy of Doravirine + Dolutegravir Dual Therapy in the Context of Antiretroviral Therapy Switch (DORDOL). Available at: https://clinicaltrials.gov/ct2/show/NCT04892654 . Accessed August 30, 2023.
Summa V, Petrocchi A, Bonelli F, et al. Discovery of raltegravir, a potent, selective orally bioavailable HIV-integrase inhibitor for the treatment of HIV-AIDS infection. J Med Chem. 2008;51:5843–5855.
De Miguel R, Montejano R, Stella-Ascariz N, et al. A safety evaluation of raltegravir for the treatment of HIV. Expert Opin Drug Saf. 2017;17:217–223.
Shah S, Hindley L, Hill A. Are new antiretroviral treatments increasing the risk of weight gain? Drugs. 2021;81:299–315.