REASONS FOR DISCONTINUATION OF DUAL THERAPY WITH DOLUTEGRAVIR AND RILPIVIRINE

Transcription

1 REASONS FOR DISCONTINUATION OF DUAL THERAPY WITH DOLUTEGRAVIR AND RILPIVIRINE R. Montejano, N. Stella-Ascariz, S. Garcia-Bujalance, JI. Bernardino, V. Hontañon, R. Mican, Montes M, E. Valencia, J. González, JR. Arribas Hospital Univesitario La Paz

2 Background Dual regimens might be an attractive option to maintain viral suppression and to avoid toxicities.

3 Nucs-Sparing Regimens Study Type of Study N Regimen Results GARDEL [1] Naive 426 LPV/RTV +3TC Similar efficacy as LPV/RTV + 2NRTIs PADDLE [2] Naive 20 DTG + 3TC Small study. Encouraging results NEAT001/A Naive 805 DRV/RTV + RAL Similar efficacy as DRV/RTV + TDF/FTC NRS143 [3] OLE [4] Switch 250 LPV/RTV + 3TC Similar efficacy as standard ART SALT [5] Switch 286 ATV/RTV + 3TC Similar efficacy as ATV/RTV + 2 NRTIs ATLAS-M [6] Switch 266 ATV/RTV + 3TC Similar (improved in post hoc analysis) efficacy vs ATV/RTV + 2NRTIs DUAL [7] Switch 260 DRV/RTV + 3TC Similar efficacy as DRV/RTV + 2NRTIs LATTE [8] Switch 243 CAB + RPV Similar efficacy as cont. standard ART LATTE-2 [9] Induction- Maintenance 309 Induct:CAB + ABC/3TC Maint: LA CAB + LA RPV im Similar efficacy as cont. oral CAB + ABC/3TC; SWORD [10] Switch 1024 DTG + RPV Similar efficacy as cont standard ART 1.Cahn P et al, EACS 2015, Abstract Figueroa MI et al EACA Abstract Raffi F, et al Lancet 2014;384: Arribas JR et al Lancet Infec Dis 2015; 15: Perez-Molina JA et al. Lancet Infect Dis 2015;15: Di Giambenedetto S, et al EACS 2015, Abstract Fulido F et al. Glasgow 2016 Abstract O Margolis DA et al. Lancet Infect Dis 2015; 15: Margolis DA et al CROI 2016 Abstract 31LB 10. Llibre JM et al CROI 2017 Abstract 2421

4 Background Dual regimens might be an attractive option to maintain viral suppression and to avoid toxicities. The aim of this study is to analyze the efficacy and safety of dolutegravir (DTG) and rilpivirine (RPV) in HIV-infected patients who switched from any other ART combination.

5 Patients and methods Retrospective cohort study All HIV-1 infected experienced patients treated with DTG+RPV from March 2015 to March 2017 in our 4000 patients HIV unit were included. Experienced HIV infected on ART N = 64 DTG + RPV

6 Patients and methods We reviewed the clinical records. The epidemiological, clinical, immuno-virological, evolution and toxicity data are presented. Descriptive analysis was done using percentages for categorical variables, and mean (standard deviation) or median (interquartile range) for continuous variables with normal or non-normal distribution, respectively.

7 Results Baseline characteristics N=64 Sex, Male 37 (57.8%) Age, years 53 (IQR 47-58) Race- Caucasian 58 (90.6%) HIV transmision -Sexual -Parenteral -Unknown 25 (39.0%) 32 (50.0%) 7 (10.9%) Time with HIV infection, years 21.7 (IQR ) Previous AIDS stage 31 (48.4%) CD4 Nadir, cells/ml 197 (IQR ) Initial VL<50 cop/ml 62 (96.88%)* Initial CD4 count, cells/ml 725 (IQR ) * 2 patients had Low level viremia <100 copies/ml Reason for switching 11% 20% 22% 47% Type of toxicity Interactions Toxicity Simplification Others 3% 3% 3% 3% Gastrointestinal Lipid alterations 34% 14% Renal Bone Urinary 17% Asthenia Liver 23% Skin

8 Previous ART history N=64 Previous Virological Failure 33 (51.5%) Previous resistance genotype - Previous VF 31 (48.%) 31/33 Number of previous ART lines 9 (IQR 6-11) ART Regimen - 2NRTI + 3 rd drug - Nucs Sparing regimen - Others 26 (40.6%) 28 (43.7%) 10 (15.6%) RT mutations 9/31 Harboured mutations that compromise RIL susceptibility 181C INI mutations No mutations were found Boosted PI containing regimen 30 (46.8 %) INI containing regimen - DTG 32 (50.0 %) 19 (59.3%) HIV evolution with this ART N=64 VL<50 copies/ml follow-up time 63 (98.4%) Supressed time (weeks) 61(IQR ) Discontinuations 13 (20.3%)

9 Reason for discontinuations 8% 46% 8% 38% Interactions Ineficacy Toxicity Others RIL interaccions: - Future HCV treatment 1/4 - Omeprazole 3/4 Persistent low level viremia No genotypic testing Type of toxicity 17% 17% 33% Renal Continuous decrease of egfr CNS Insomnia 33% Gastrointestinal Muscle pain

10 Conclusions DTG+RPV was an effective regimen in this small cohort of patients with long time of HIV infection and prior ART failure There was an unexpected number of discontinuations due mainly to toxicity and drug to drug interactions. Despite prior resistant mutations, not virological failures with resistance development were found.