Characterization of viral rebounds on dual etravirine/raltegravir maintenance therapy (ANRS-163 ETRAL trial). (7th April 2020)

• Record Type: Journal Article
• Authors: Soulie, Cathia; Assoumou, Lambert; Abdi, Basma; Sayon, Sophie; Nguyen, Thuy; Valantin, Marc-Antoine; Beniguel, Lydie; Ferre, Virginie; Alloui, Chakib; Montes, Brigitte; Avettand-Fenoel, Véronique; Delaugerre, Constance; Descamps, Diane; Martinez, Esteban; Reynes, Jacques; Peytavin, Gilles; Costagliola, Dominique; Katlama, Christine; Calvez, Vincent; Marcelin, Anne-Geneviève
• Is Part Of: Journal of antimicrobial chemotherapy. Volume 75:Number 7(2020)
• Page Start: 1943
• Page End: 1949
• Publication Date: 2020-04-07
• Subjects: Anti-infective agents -- Periodicals; Chemotherapy -- Periodicals; 615.58
• DOI: 10.1093/jac/dkaa090
• Languages: English
• ISSNs: 0305-7453

Abstract

Abstract: Background: The ANRS-163 ETRAL trial, a switch study to an etravirine 200 mg/raltegravir 400 mg twice-daily regimen in 165 patients with HIV-1 infection, showed durable efficacy until Week 96. The aim of this work was to investigate in detail the virological rebounds (VRs), defined as at least one plasma HIV viral load (VL) >50 copies/mL. Methods: Quantification of HIV-DNA level was assessed at baseline, Week 48 and Week 96 ( n = 157). VLs were measured in seminal plasma at Week 48 ( n = 26). Genotypic resistance testing by ultra-deep sequencing (UDS) for reverse transcriptase (RT) and integrase regions was performed at baseline and at the time of VR. Results: In this study, 19 patients experienced VR, with 2 patients having virological failure (VF; two consecutive VLs >50 copies/mL). For the first patient with VF, UDS detected minority resistant variants only in RT (K103N, 9.6%; Y181C, 4.9%) at baseline. Some RT variants became dominant at VF (K101E, 86.3%; Y181C, 100.0%; G190A, 100.0%) and others emerged in integrase (Y143C, 2.4%; Q148R, 6.2%; N155H, 18.8%). For the second patient with VF, neither RT nor integrase mutations were detected at baseline and VF. Median HIV-DNA level was similar at baseline, Week 48 and Week 96 (2.17, 2.06 and 2.11 log10 copies/10 6 cells, respectively). Only one patient had a detectable seminal HIV VL (505 copies/mL). Conclusions: The dual etravirine/raltegravir regimen as maintenance therapy was effective and the emergence of mutations in cases of VF was similar to that seen in other dual-regimen studies. No HIV-DNA level modification was evidenced by Week 96.