Antiretroviral drug reduction in highly experienced HIV-infected patients receiving a multidrug regimen: the ECOVIR study Marc-Antoine Valantin 1 *, Lise Durand 2 , Marc Wirden 3 , Lambert Assoumou 4 , Fabienne Caby 1 , Cathia Soulie ´ 3 , Thi Thu-Thuy Nguyen 3 , Roland Tubiana 1 , Myriam Kirstetter 5 , Helga Junot 2 , Anne-Genevie ` ve Marcelin 3 , Gilles Peytavin 6 , Patrick Tilleul 2,7 and Christine Katlama 8 1 AP-HP, Ho ˆ pitaux Universitaires Pitie ´ Salpe ˆtrie `re - Charles Foix, Service des Maladies Infectieuses, Sorbonne Universite ´ , INSERM, Institut Pierre Louis d’Epide ´ miologie et de Sante ´ Publique, (IPLESP UMRS 1136), F-75013, Paris, France; 2 GH Pitie ´-Salpe ˆtrie ` re APHP, Pharmacy, Paris, France; 3 INSERM, Sorbonne Universite ´ , Institut Pierre Louis d’Epide ´ miologie et de Sante ´ Publique (IPLESP UMRS 1136), AP-HP, Ho ˆ pital Pitie ´ -Salpe ˆtrie `re, Laboratoire de virologie, F-75013, Paris, France; 4 INSERM, Sorbonne Universite ´ , Institut Pierre Louis d’Epide ´ miologie et de Sante ´ Publique (IPLESP UMRS 1136), Paris, France; 5 AP-HP, Ho ˆ pitaux Universitaires Pitie ´ Salpe ˆtrie ` re - Charles Foix, Service des Maladies Infectieuses, Paris, France; 6 IAME, UMR 1137, INSERM, Universite ´ Paris Diderot, Sorbonne Paris Cite ´ , AP-HP, Laboratoire de Pharmacologie-Toxicologie, Ho ˆ pital Bichat Claude-Bernard, Paris, France; 7 Paris Descartes Universite ´ , Pharmacie Clinique, Faculte ´ de Pharmacie, Paris, France; 8 Sorbonne Universite ´ , INSERM, Institut Pierre Louis d’Epide ´ miologie et de Sante ´ Publique, (IPLESP UMRS 1136), AP-HP, Ho ˆ pitaux Universitaires Pitie ´ Salpe ˆtrie ` re - Charles Foix, Service des Maladies Infectieuses, F-75013, Paris, France *Corresponding author. Department of Infectious Diseases, Ho ˆ pital Pitie ´-Salpe ˆtrie `re, Sorbonne University Paris, Paris, France. Tel: !33 1 42 16 01 44; Fax: !33 1 42 16 01 26; E-mail: marc-antoine.valantin@aphp.fr Received 1 February 2019; returned 18 March 2019; revised 6 May 2019; accepted 22 May 2019 Objectives: In a context of life-long therapy, we asked whether it could be possible to reduce the number of anti- retroviral drugs without jeopardizing viral suppression. Methods: ECOVIR was a prospective study aiming to assess whether in patients on combination ART with 4 antiretrovirals for 24 weeks and virally suppressed for 48 weeks, a drug-reduced (DR) regimen could be pro- posed. The intervention consisted of discontinuing genotypically less susceptible drugs to reach a DR regimen with 3 antiretrovirals. The primary endpoint was the proportion of patients maintaining viral suppression at week (W) 24. Results: From 89 eligible individuals for the study, a DR regimen was proposed in 86 (97%) patients, of whom 71 were switched to a DR regimen. Baseline characteristics [median (IQR)] were: age 58 (53–65) years, duration of treatment 24 (21–26) years and viral suppression 8 (6–11) years. The cumulative resistance profile showed full resistance to lamivudine/emtricitabine (91%), abacavir (74%), efavirenz/nevirapine (70%), rilpivirine (56%), dar- unavir (q24h/q12h) (42%/29%), lopinavir (69%), atazanavir (71%) and raltegravir (24%). The final DR regimen consisted of a two-drug or three-drug regimen in 54 patients (76%) and in 17 patients (24%), respectively. The success rate of a DR regimen at W24 was 93.9% (95% CI 84.4–97.6, Kaplan–Meier estimate). Four patients expe- rienced virological failure (at W4, W8 and W12), all with plasma viral load (pVL) ,600 copies/mL and no emer- gence of resistance mutations. The DR strategy allowed a monthly cost saving of 36%. Conclusions: In experienced patients with high-level resistance, individualized strategies based on expert advice can offer DR regimen options with fewer drug–drug interactions and a significant economic impact while ensur- ing virological success. Introduction The goal of combined ART (cART) is to sustain viral suppression in order to minimize HIV disease progression, optimize immune res- toration and prevent interindividual transmission. 1,2 In the ab- sence of cure or remission strategies, life-long therapy is needed to stop viral replication. 3,4 There is a growing interest in drug- reducing antiretroviral strategies in order to lower cumulative tox- icity and drug exposure. Until the mid 2000s, in a context of non-suppressive regimens, patients had accumulated periods of viral replication on ART lead- ing to multiple resistance-associated mutations. Fortunately, V C The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com. 2716 J Antimicrob Chemother 2019; 74: 2716–2722 doi:10.1093/jac/dkz255 Advance Access publication 4 July 2019 Downloaded from https://academic.oup.com/jac/article/74/9/2716/5528379 by guest on 10 June 2022