|Final Week 48 Analysis of Cenicriviroc (CVC) Compared to Efavirenz (EFV), in Combination with Emtricitabine/Tenofovir (FTC/TDF), in Treatment-naïve HIV-1-infected Adults with CCR5-Tropic Virus|| |
|J. Feinberg1, M. Thompson2, J. Cade3, E. De Jesus4, J. Gathe5, J. Lalezari6, A. Scarsella7, M. Saag8, J. Enejosa9, E. Lefebvre9|
|1University of Cincinnati, Cincinnati, United States, 2AIDS Research Consortium of Atlanta, Atlanta, United States, 3Nevada AIDS Research and Education Society, Las Vegas, United States, 4Orlando Immunology Center, Orlando, United States, 5Therapeutic Concepts, Houston, United States, 6Quest Clinical Research, San Francisco, United States, 7Pacific Oaks Medical Group, Beverly Hills, United States, 8University of Alabama at Birmingham, Birmingham, United States, 9Tobira Therapeutics, Inc., San Francisco, United States|
|Objectives: Cenicriviroc is a novel, once-daily, potent, dual CCR5/CCR2 antagonist. This Phase 2b, double-blind, double-dummy, 48-week study (NCT01338883) compared CVC with EFV, each with FTC/TDF, in treatment-naïve HIV-1-infected subjects.|
Methods: Adults with HIV-1 RNA ≥1000c/mL, CD4+ ≥200cells/mm3, CCR5-tropic virus randomised 2:2:1 to receive CVC 100mg or 200mg (after breakfast) or EFV (at bedtime), with FTC/TDF. Objectives ‑ % subjects with HIV-1 RNA < 50c/mL; safety; emerging resistance and tropism changes.
Results: 143 subjects randomised and treated: 94% male; 62% Caucasian, 32% African-American; 20% baseline HIV-1 RNA ≥100 000c/mL; mean baseline CD4+ 402cells/mm3. Attrition was high overall (30%) and greater with EFV than CVC; 13% of all randomised subjects discontinued for reasons other than efficacy or safety. Week 48 virologic success (FDA Snapshot; ITT) was 68%, 64% and 50% for CVC 100mg, CVC 200mg and EFV, respectively. Week 48 virologic non-response was 15%, 20% and 11% for CVC 100mg, CVC 200mg and EFV, respectively. Of 11 subjects with protocol-defined virologic failure (PDVF: confirmed HIV-1 RNA ≥400c/mL on or after Week 12, or never achieved < 50c/mL by Week 24), NRTI resistance mutations (all at codon 184) emerged in 75%, 33% and 0% in the CVC 100mg, CVC 200mg and EFV arms. One PDVF subject in CVC 200mg arm changed tropism from R5 to D/M. Fewer CVC than EFV subjects had Grade 3 or 4 adverse events (AEs) or discontinued due to AEs. Total- and LDL-cholesterol decreased significantly with CVC but increased with EFV (p< 0.05).
|Summary of Week 48 analysis||CVC 100mg|
|Virologic success (HIV-1 RNA <50c/mL; Snapshot - ITT), n (%)||40 (68%)||36 (64%)||14 (50%)|
|Virologic non-response (Snapshot - ITT), n (%)||9 (15%)||11 (20%)||3 (11%)|
|No virologic data in Week 48 window (Snapshot - ITT), n (%)||10 (17%)||9 (16%)||11 (39%)|
|• Discontinued due to AE, n (%)||0 (0%)||1 (2%)||6 (21%)|
|• Discontinued for other reasons, n (%)||8 (14%)||7 (13%)||3 (11%)|
|• Missing data in window but still on study, n (%)||2 (3%)||1 (2%)||2 (7%)|
|NRTI resistance mutations in subject with PDVF, n/N (%)||3/4 (75%)||2/6 (33%)||0/1 (0%)|
|Mean change in CD4+ count from baseline to Week 48, cells/mm3
|Treatment-emergent Grade 3 or 4 AEs, n (%)||2 (3%)||3 (5%)||4 (15%)|
[Summary of Week 48 analysis]
More CVC-treated subjects were evaluable at Week 48; CVC was associated with higher rates of Snapshot virologic success but also higher rates of virologic non-response compared to EFV. NRTI resistance was only seen with CVC and less frequently with 200mg dose. CVC resulted in fewer Grade 3 or 4 AEs and discontinuations due to AEs than EFV.
Judith Feinberg , University of Cincinnati , Cincinnati , United States
Assigned in sessions:
17.10.2013, 14:00-16:00, Parallel Session, PS4, Antiretroviral Therapy I, Bozar (Plenary Hall)