HYNES CONVENTION CENTER

Boston, Massachusetts
March 4–7, 2018

 

Conference Dates and Location: 
February 13–16, 2017 | Seattle, Washington
Abstract Number: 
42

PATHWAYS OF RESISTANCE IN SUBJECTS FAILING DOLUTEGRAVIR MONOTHERAPY

Author(s): 

José L. Blanco1, Celia Oldenbuettel2, Réjean Thomas3, Josep Mallolas1, Eva Wolf4, Bluma Brenner5, Christoph D. Spinner6, Mark A. Wainberg5, Esteban Martinez1

1Hosp Clinic Barcelona, Barcelona, Spain,2MVZ Karlsplatz, HIV Rsr and Clinical Care Cntr, München, Germany,3Clinique Médicale l'Actuel, Montreal, Canada,4MUC Rsr, Munich, Germany,5McGill Univ, Montreal, Quebec, Canada,6Univ Hosp Klinikum Rechts der Isar, Munich, Germany

Abstract Body: 

Dolutegravir (DTG) is a second generation InSTI that has shown in both preclinical and clinical studies to have a higher barrier to resistance than first generation InSTIs (RAL and EVG).To date, no InSTI resistance-associated mutations (RAMs) have been reported in ART-naïve persons receiving DTG through 144 weeks of follow-up in clinical trials and very few cases has been reported in INSTI-naïve subjects among pretreated individuals. Our objective was to identify and characterize different pathways of resistance in subjects failing a DTG-monotherapy (DTG-M) in four large clinical cohorts

This is an international, multi-cohort, retrospective study. All subjects with no prior InSTI virological failure (InSTI-VF) failing DTG-M were included in this analysis. Virological failure (VF) was defined as two plasma viral loads (VL) above 50 cp/mL. Genotypic resistance mutations could be detected by: (i) plasma population sequencing (PS); (ii) plasma ultra-deep sequencing test (UDS); peripheral blood mononuclear cell population sequencing (PBMC-PS); and PBMC-UDS

Three large clinical cohorts in Munich, Montreal and Barcelona were included in this analysis. A total of 178 ART-experienced subjects with no prior InSTI-VF changed from different ART-regimens to DTG monotherapy (DTG-M). Eleven (6.1%) had VF and 7 (3.9%) selected any InSTI-RAMs . Two of 7 were women, median (range) of previous VF 1 (0-8; 3: 0VF; 1:1VF; 3≥4). InSTI prior DTG was: 3 none, 3 RAL and 1 EGV. VL by the time of starting DTG-M was: 5= below the lower limits of detection (LLOD), 1=249 cp/mL and 1=21 cp/mL. Reasons for switch to DTG-M were: simplification (n=2), DDI (n=3), patient decision (n=3), toxicity (n=1), VF (n=1); 5 patients had at least one LLOD before VF. Median (range) time and first VL by the time of VF were 12 weeks (0-28) and 306 copies/mL (55-26180), respectively. Time to first detection of DTG-RAMs was 28 weeks (2-32). The three different pathways by the time of VF were: 148R/H in 3 patients, 155H in 2, and 118R in 2

Virological failure and selection of InSTI-RAMs are uncommon but they may exist in patients with no prior InSTI virological failure subjects on DTG-monotherapy. Different pathways, similar to first-generation InSTIs (RAL and EVG), 148R/H, 155H, and 118R were identified in these cases

Session Number: 
O-4
Session Title: 
NEW HIV DRUGS, FORMULATIONS, COMBINATIONS, AND RESISTANCE
Presenting Author: 
José Blanco
Presenter Institution: 
Hospital Clinic