7th IAS Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2013)

Abstract

WEPE515 - Poster Exhibition


Intelence aNd daRunavir Once a Day Study (INROADS): a multicenter, single-arm, open-label study of once daily combination of etravirine (ETR) and darunavir/ritonavir (DRV/r) as dual therapy in early treatment-expe

P. Ruane1, C. Brinson2, P. Kumar3, E. Dejesus4, R. Ryan5, M. Cho6, D. Anderson6

1Peter J Ruane MD, Inc., Los Angeles, United States, 2Central Texas Clinical Research, Austin, United States, 3Georgetown University School of Medicine, Washington, United States, 4Orlando Immunology Center, Orlando, United States, 5Janssen Research & Development, Titusville, United States, 6Janssen Services, LLC, Titusville, United States

Background: Most ARV regimens contain 3 active agents and include nucleosides/tides. Nucleoside-sparing regimens consisting of a RTV-boosted PI combined with another class may offer an alternative approach but have been less studied, particularly in treatment-experienced subjects. DRV/r combined with ETR, both potent agents with high genetic barriers to resistance and pharmacokinetics permitting once-daily (qd) co-administration, may provide a well-tolerated, effective qd ARV regimen.
Methods: Phase 2, single-arm, open-label, multicenter, 48-week trial evaluating the efficacy and safety of ETR 400mg and DRV/r 800/100mg qd in HIV-1-infected adults who were treatment-experienced or treatment-naïve with transmitted resistance. Treatment-experienced eligible subjects had ≤2 previous virologic failures (VFs) while on PI-containing regimens. All subjects demonstrated full genotypic/phenotypic sensitivity to DRV and ETR.
Results: Fifty-four subjects (78% male; 48% Black) were enrolled; 41 (76%) completed the study. Baseline mean log10 HIV-1 RNA was 3.9 copies/mL; median CD4+ cell count was 333 cells/µl. Forty-two (78%) were treatment-experienced and 12 (22%) were treatment-naive.Confirmed virologic response at Week 48 (W48) in the ITT non-VF censored group (primary endpoint) was 89% (95% confidence interval 79.7, 98.1). Four (7%) subjects withdrew for adverse events (AEs) and 4 (7%) for reaching a virologic endpoint. The median change in CD4+ cell count from baseline to W48 was 149 cells/µl. The two VF subjects with baseline and withdrawal resistance testing available had ETR resistance mutations. No new PI resistance-associated mutations were identified. No differences in outcomes were noted by gender.The most common AEs were diarrhea (n=8; 15%), upper respiratory tract infection (n=6; 11%) and rash (n=6; 11%). Three subjects (6%) experienced serious AEs: fatigue, pyrexia, Hodgkin's disease, dyspnea; jaw abscess; pneumonia. Four subjects experienced grade 2-4 AEs at least possibly related to study drug: increased LDL, hyperlipidemia, and rash.From baseline to W48, elevated lipids, including LDL (Δ of 17.9mg/dL), HDL (8.7mg/dL), total cholesterol (30.1mg/dL) and triglycerides (28.9mg/dL) were observed. Total cholesterol:HDL ratio, fasting glucose and insulin levels remained relatively unchanged.
Conclusion: ETR and DRV/r qd as a two-drug, regimen in treatment-experienced or treatment-naïve with transmitted resistance subjects was generally effective and well-tolerated, with little resistance development and mild/moderate lipid elevations.

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