Abstract PE7/14
 
A Retrospective Comparison of Etravirine (ETR) and Darunavir/Ritonavir (DRV/r) as Dual Therapy in Early Treatment-experienced Subjects (INROADS) to a Matched Historical Control Cohort Print
 
P. Ruane1, J. Morales-Ramirez2, H. Katner3, C.-B. Hsiao4, B. Coate5, R. Ryan6, M. Cho7, D. Anderson7
1Peter J Ruane MD Inc, Los Angeles, United States, 2Clinical Research Puerto Rico, San Juan, Puerto Rico, 3Mercer University School of Medicine, Macon, GA, United States, 4Allegheny General Hospital, Pittsburgh, PA, United States, 5Independent Contractor for Janssen Research & Development, Titusville, United States, 6Janssen Research & Development, Titusville, NJ, United States, 7Janssen Services, LLC, Titusville, United States
 
Objectives: INROADS (Intelence aNd PRezista Once A Day Study; NCT01199939) was a single-arm trial that assessed DRV/r and ETR as a nuc-sparing, 2-drug therapy in early treatment-experienced adults. This analysis compared results from INROADS with those from matched historical controls (HCs).
Methods: Phase 2, 48-week trial evaluating efficacy and safety of once-daily ETR 400mg and DRV/r 800/100mg in HIV-1-infected treatment-experienced or treatment-naïve with transmitted resistance adults. INROADS subjects were retrospectively compared with HCs from the GRACE, ODIN, and TITAN (up to Week 48) phase 3 DRV trials, in which patients were treated with ≥3 ARVs including NRTIs. Subjects were matched by baseline CD4 count, viral load, race, and HIV CDC disease stage. For ties, the closest match to CD4 count was retained.
Results: 52 out of 54 subjects enrolled in INROADS were matched to HCs. 79% were male and 48% were Black/African-American. Baseline mean log10 HIV-1 RNA was 4 log copies/mL; baseline median CD4 count was 334 cells/µl for INROADS and 333 cells/µl for HCs. All subjects demonstrated full genotypic/phenotypic sensitivity to DRV and ETR. All subjects in HC were treatment-experienced; 12 subjects (23%) in INROADS were treatment-naïve but with transmitted resistance. Confirmed virologic response at Week 48 (W48) in the ITT non-VF censored group (primary endpoint) was higher in INROADS than HCs (Table 1), as were increases in CD4 count from baseline to W48. VF rates were low, but more common in INROADS than HCs (Table 2). No clinically relevant differences in laboratory parameters or safety were observed between INROADS and HCs, although increases in glucose were slightly higher in INROADS (Tables 3 and 4).
Efficacy parametersINROADS (N=52)HC (N=52)
CVR, ITT non-VF censoreda, n/N (%) [95% CI]40/45 (89) [79.7, 98.1]30/44 (68) [54.4, 81.9]
CVR, ITT, n/N (%) [95% CI]40/52 (77) [65.5, 88.4]30/52 (58) [44.3, 71.1]
CVR, ITT-TLOVR, n/N (%) [95% CI]40/52 (77) [65.5, 88.4]30/52 (58) [44.3, 71.1]
FDA snapshot analysis, ITT, n (%)37 (71)31 (60)
Median (range) CD4+ cell count change from BL to W48 (cells/μL)148.5 (-259, 564)84.5 (-242, 395)
[Table 1]
DispositionINROADS (N=52)HC (N=52)
Discontinued, n (%)11 (21)10 (19)
Virologic failure4 (8)2 (4)
AE3 (6)2 (4)
Lost to follow-up1 (2)3 (6)
Protocol violation3 (6)0
Noncompliant02 (4)
Withdrew consent01 (2)
[Table 2]
Safety analysisINROADS (N=52)HC (N=52)
Subjects with ≥1 Grade 3/4 AE regardless of causality, n (%)9 (17)7 (14)
Grade 3/4 AEs regardless of causality occurring in ≥2 subjects  
Blood amylase increased2 (4)0
Subjects with ≥1 Grade 2-4 AE at least possibly related to treatment, n (%)4 (8)11 (21)
Grade 2-4 AEs at least possibly related to treatment occurring in ≥2 subjects  
Diarrhea02 (4)
Nausea03 (6)
Vomiting03 (6)
Rash2 (4)1 (2)
[Table 3]
Change in lipids and glucose from BL to W48, mean ± SD (n)INROADS (N=52)HC (N=52)
Glucose, mmol/L0.30 ± 0.895 (40)-0.12 ± 0.639 (39)
LDL, mmol/L0.46 ± 0.952 (40)0.14 ± 0.824 (36)
HDL, mmol/L0.22 ± 0.338 (40)0.03 ± 0.231 (38)
Total cholesterol, mmol/L0.78 ± 1.028 (40)0.38 ± 1.022 (39)
Cholesterol/HDL ratio-0.07 ± 1.615 (40)0.20 ± 0.932 (38)
Triglycerides, mmol/L0.33 ± 2.003 (40)0.45 ±1.238 (39)
Apo A1, g/L0.20 ± 0.234 (38)-1.12 ± 9.639 (38)
Apo B, g/L0.09 ± 0.236 (38)-0.34 ± 8.984 (38)
[Table 4]

Conclusion: In this small study, ETR and DRV/r qd as a 2-drug regimen in early treatment-experienced subjects resulted in higher response rates compared to HCs, with no clinically relevant differences in safety observed.


Assigned speakers:
Javier Morales-Ramirez , Puerto Rico

Assigned in sessions:
17.10.2013, 12:00-14:00, Poster Session, Poster Session 1, Exhibition
18.10.2013, 12:00-14:00, Poster Session, Poster Session 2, Exhibition