CROI 2017 Abstract e-Book

Abstract eBook

Oral Abstracts

spread across the Netherlands having +/-80% of Dutch HIV+MSM in care. We compared the incidence in 2014 (year preceding DAA availability) to 2016 incidence (first year after DAA availability). Results: In 2014, 93 AHCV infections occurred in 8290 PYFU (=11.2/1000 PYFU, 95% CI 9.1-13.7). In 2016, 49 AHCV were diagnosed in 8961 PYFU (=5.5/1000 PYFU, 95% CI 4.1–7.2, p<0.001). The incidence in 2014 of 11.2/1000 showed a continuous decline to 6.9/1000 and 4.0/1000 within the first and second half of 2016. A relative increase in genotype 4 infections was observed from 19% (n=18) to 31% (n=15) (p=0.02). The absolute number of AHCV infections decreased both in patients with a first AHCV infection as well as in patients that had an AHCV reinfection (=patients previously cured of an AHCV infection), while the proportion of reinfections remained constant: 21/93 in 2014 and 12/49 in 2016 (p=0.8). Conclusion: 1 year after unrestricted DAA availability in the Netherlands, the incidence of acute HCV in HIV+MSM decreased by 52%. For the first time, real-life data show that “HCV treatment as prevention” averts new HCV infections in HIV+MSM. 138 CORRELATION OF RENAL BIOMARKERS AND TENOFOVIR AUC IN THE ION-4 STUDY COHORT Austin W. Chan 1 , Larry Park 1 , Lauren F. Collins 1 , Curtis Cooper 2 , Michael Saag 3 , Douglas Dieterich 4 , Mark Sulkowski 5 , Susanna Naggie 1 , for the ION-4 Study Group 1 Duke Univ, Durham, NC, USA, 2 Ottawa General Rsr Inst, Ottawa, Ontario, 3 Univ of Alabama at Birmingham, Birmingham, AL, USA, 4 Icahn Sch of Med at Mt Sinai, New York, NY, USA, 5 The Johns Hopkins Univ, Baltimore, MD, USA Background: The ION-4 study assessed the safety and efficacy of ledipasvir/sofosubvir (LDV/SOF) for 12 weeks in patients with chronic HIV and HCV infections. Concomitant dosing of ledipasvir and tenofovir disoproxil fumarate (TDF) results in increased tenofovir (TFV) area under the curve (AUC). Retinol binding protein-4(RBP4) and β2- microglobulin(B2M) are currently the most reliable urinary biomarkers for detecting proximal tubule dysfunction. The aim of this study was to examine whether there was a correlation between urinary biomarkers RBP4 and B2M and renal toxicity and TFV AUC. Methods: The ION-4 trial enrolled HIV/HCV patients on antiretroviral regimens with TDF containing nucleoside reverse transcriptase inhibitor (NRTI) backbones. Plasma TFV concentrations were collected on treatment at 12 and 24 hours and 4, 6, 8, 10, 12 weeks. Urine RBP4 and B2M, urine protein and serum creatinine were collected at multiple time points on and post-treatment. We assessed changes in urinary biomarkers throughout the study period and associations with clinically relevant changes in renal function [creatinine clearance decrease >25%, creatinine >0.2 mg/dL, incident proteinuria (negative/trace to ≥ 1+) and TFV AUC and other pharmacokinetic parameters. Results: 335 patients enrolled in the ION-4 study with demographic characteristics that have been previously described. Overall 19 (5.67%) patients had creatinine clearance decrease >25%, 42 (12.5%) creatinine >0.2 mg/dL, and 114 (34.0%) had an increase in urine proteinuria from negative/trace to ≥ 1+. RBP4 increased from baseline to end of therapy in all subgroups of renal dysfunction. B2M did not demonstrate a similar change from baseline to end of therapy for any subgroup of renal dysfunction. Baseline levels of RBP4 and B2M were higher for patients with incident proteinuria (p<0.001), this was true for the other measures of renal dysfunction but was not statistically significant. Both RBP4 and B2M exhibited positive correlations with tenofovir AUC (Figure 1). Conclusion: Drug interactions with antiretrovirals and direct acting antivirals are common in patients with HIV/HCV co-infection. Urinary biomarkers are elevated at baseline in patients who experience incident proteinuria during concomitant dosing of ledipasvir and TDF and correlate with serum TFV AUC. Urinary biomarkers, specifically RBP4, may identify patients at risk of tubular toxicity who have increased exposures to TFV.

Oral Abstracts

139 HEPATOCELLULAR CARCINOMA AFTER SVR WITH IFN-FREE REGIMENS IN HIV/HCV COINFECTION Nicolás Merchante 1 , Boris Revollo 2 , Francisco Rodríguez-Arrondo 3 , Esperanza Merino 4 , Maria J. Galindo 5 , Marta Montero 6 , Antonio Rivero-Juárez 7 , Marcial Delgado-Fernández 8 , Maria J. Rios-Villegas 9 , Juan A. Pineda 1 1 Hosp Univ de Valme, Sevilla, Spain, 2 Hosp German Trias i Pujol, Badalona, Spain, 3 Hosp Univ de Donostia, San Sebastián, Spain, 4 Hosp General Univ de Alicante, Alicante, Spain, 5 Hosp Clínico de Valencia, Valencia, Spain, 6 Hosp Univ y Politécnico La Fe, Valencia, Spain, 7 Hosp Univ Reina Sofía, Córdoba, Spain, 8 Hosp Regional Univ de Málaga, Málaga, Spain, 9 Hosp Univ Virgen Macarena, Sevilla, Spain Background: The consecution of sustained virological response (SVR) is associated with a reduction in the risk of liver-related events, including hepatocellular carcinoma (HCC), and liver-related mortality in HIV/HCV-coinfected patients. However, HIV/HCV-coinfected patients who achieve SVR are still at risk of developing HCC. It is not known if the risk of developing HCC after SVR has been modified with the arrival of all-oral direct antiviral agents (DAA) interferon (IFN)-free regimens. Our objective was to assess the proportion of HCC cases diagnosed after SVR in HIV/HCV-coinfected patients and its evolution over time. Methods: The GEHEP-002 multicentric cohort (ClinicalTrials.gov ID: NCT02785835) recruits HCC cases diagnosed in HIV-infected patients from 32 centers from Spain. The proportion of HCC cases after SVR and the evolution of this proportion over time were analyzed. For this purpose, we define 4 periods of time according to the changes of treatment strategies for hepatitis C in Spain: 1) Period 1 (≤ 2001): non-pegylated IFN; 2) Period 2 (2002-2011): pegylated IFN plus ribavirin; 3) Period 3 (2011-October 2014): DAA in combination with IFN and 4) Period 4 (October 2014-September 2016): DAA IFN-free regimens.

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CROI 2017