CROI 2016 Abstract eBook

Abstract Listing

Poster Abstracts

574 TURQUOISE-I Part 1b: Ombitasvir/Paritaprevir/r+Dasabuvir+RBV for HCV/HIV Coinfection

David L. Wyles 1 ; Michael S. Saag 2 ; RogerTrinh 3 ; Jacob Lalezari 4 ; Oluwatoyin Adeyemi 5 ; Laveeza Bhatti 6 ; Amit Khatri 3 ;Yiran B. Hu 3 ; Nancy S. Shulman 3 ; Peter Ruane 7 1 Univ of California San Diego, San Diego, CA, USA; 2 Univ of Alabama at Birmingham, Birmingham, AL, USA; 3 AbbVie Inc, North Chicago, IL, USA; 4 Quest Clinical Rsr, San Francisco, CA, USA; 5 Ruth M. Rothstein CORE Cntr, Chicago, IL, USA; 6 AIDS Hlthcare Fndn, Beverly Hills, CA, USA; 7 Peter J Ruane MD, Inc, Los Angeles, CA, USA Background: The 3 direct-acting antiviral (DAA; 3D) regimen of ombitasvir/paritaprevir/ritonavir (OBV/PTV/r; PTV identified by AbbVie and Enanta) with dasabuvir (DSV) ± ribavirin (RBV) is approved in the US and EU for hepatitis C virus (HCV) genotype 1 (GT1) in patients with HIV‑1 co‑infection. In healthy volunteers, co-administration of 3D+darunavir (DRV) did not significantly change DAA exposures; however, DRV C trough levels were 48% and 43% lower with once and twice daily (QD and BID) DRV co- administration, respectively. To assess the clinical significance of co-administration, Part 1b of TURQUOISE-I evaluates efficacy and safety of 3D+RBV in patients with HCV GT1/ HIV‑1 co‑infection on stable DRV-containing antiretroviral therapy (ART). Methods: Eligible patients were HCV treatment-naïve/interferon-experienced, had CD4+ count ≥200cells/mm 3 or ≥14%, and plasma HIV-1 RNA suppression on stable QD DRV- containing ART at screening. Patients were randomized to maintain DRV 800mg QD or switch to DRV 600mg BID during a pre-treatment period. All patients received 3D+RBV for 12 weeks. Virologic response and safety from a data cut on 23Sept2015 are reported in this abstract. Results: Twenty-two patients were enrolled: 77%male, 41% identified as black race, 27% as Hispanic ethnicity, 68% HCV GT1a-infected, and 18%with cirrhosis. All patients with available data achieved sustained virologic response (HCV RNA <25IU/mL) at post-treatment weeks 4 (17/17) and 12 (13/13). No DAA-related severe or serious adverse events (AEs) or AEs leading to discontinuation were reported. The most common AEs (>15% of patients) were fatigue (36%), hemoglobin decreased (23%), irritability (23%), and nausea (18%). Intensive pharmacokinetic evaluations revealed that co-administration of DRV and 3D+RBV resulted in minimal impact on DRV C max and AUC; however, DRV C trough levels were 53% and 29% lower with DRV QD and BID, respectively. All but one patient with available data (DRV BID arm) had HIV-1 RNA suppression at end of treatment based on the FDA snapshot algorithm (single HIV-1 RNA of 64copies/mL), though this patient maintained HIV-1 RNA <40copies/mL at all other visits. No patient experienced plasma HIV-1 RNA >200 copies/ mL during the treatment period. Conclusions: Patients with HCV GT1/HIV-1 co-infection on stable DRV-containing ART achieve high SVR rates while maintaining plasma HIV-1 RNA suppression. Despite changes in DRV exposures, episodes of intermittent HIV-1 viremia were infrequent during the study.

Poster Abstracts

575 NS5A and NS5B Minor Variant Analyses in HCV/HIV Patients Failing Treatment With DCV/SOF Dennis Hernandez 1 ; Saumya Pant 2 ; Nannan Zhou 1 ; Fiona McPhee 1 1 Bristol-Myers Squibb, Wallingford, CT, USA; 2 Bristol-Myers Squibb, Princeton, NJ, USA

Background: ALLY-2 was a phase 3 study of daclatasvir (DCV) plus sofosbuvir (SOF) for 12 or 8 weeks in patients with HIV/HCV coinfection. Thirteen patients in ALLY-2 experienced relapse; 2 in the 12-week and 11 in the 8-week group. Emergent drug-resistant variants were mostly not detected in the 8-week group by standard sequencing methods. We assessed the presence of minor variants among the 13 patients who experienced relapse. Methods: Plasma samples drawn at baseline and relapse from the 13 HCV/HIV coinfected patients who relapsed were prepared for next-generation sequencing (NGS) of the HCV NS5A and NS5B regions using the Illumina MiSeq sequencing platform at DDL Diagnostic Laboratories (NL). NS5A amino acids 28, 29, 30, 31, 32, 58, 62, 92, and 93 and NS5B amino acids 61, 112, 159, 237, 282, 320, 321, and 473 were monitored using NGS (sensitivity cut-off 1%) and results compared with standard direct sequencing (DS; sensitivity cut-off 25%). Results: NS5A NGS and DS results were concordant at failure for both patients (both genotype [GT]1a) who relapsed after 12 weeks of DCV/SOF treatment (Table). Of these 2 patients, 1 had minor variants (M28V [1.1%], E62D [16.9%]) at baseline that were not observed at failure with emergent NS5A-Q30R. The other patient had NS5A-Y93N at baseline that was enriched with emergent NS5B-L159F and the minor variant NS5B-E237G. Eight of the 11 patients failing 8 weeks of treatment (5/8 GT1a, 1/1 GT1b, 1/1 GT2, 1/1 GT3) had no pre-existing or emergent minor variants to NS5A, however 1 of the GT1a patients had NS5B-D61G (1.6%) emerge (Table). Three patients (all GT1a) had minor NS5A variants emerge (Q30R [2.1%] or M28T [5.4%] and L31M [1.1%] or Y93C [1.0%]). The patient with Y93C also had M28L (1.9%) at baseline that was not detected at failure. No NS5B RAVs were detected in these 3 patients. For the single patient in the 8-week group with previously reported emergent NS5A-Q30E by DS, no minor variants to NS5A or NS5B emerged. For patients with emergent minor variants to NS5A, these will be further monitored to assess decay. Conclusions: In ALLY-2, there was no impact of baseline NS5A or NS5B minor variants on response as these variants were not enriched at failure.

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CROI 2016