CROI 2020 Abstract eBook

Abstract eBook

Poster Abstracts

573 A MULTICENTER REGISTRY IN PATIENTS WITH HIV/HCV COINFECTION ON LEDIPASVIR/SOFOSBUVIR Stefan Mauss 1 , Cody A. Chastain 2 , Nwora L. Okeke 3 , Kristen M. Marks 4 , Kimberly Workowski 5 , Gregory K. Robbins 6 , Kenneth E. Sherman 7 , Chris Woods 8 , Lawrence Park 3 , Jürgen K. Rockstroh 9 , Susanna Naggie 10 1 Center for HIV and Hepatogastroenterology, Düsseldorf, Germany, 2 Vanderbilt University, Nashville, TN, USA, 3 Duke University School of Medicine, Durham, NC, USA, 4 Weill Cornell Medicine, New York, NY, USA, 5 Emory University, Atlanta, GA, USA, 6 Massachusetts General Hospital, Boston, MA, USA, 7 University of Cincinnati, Cincinnati, OH, USA, 8 Durham VA Medical Center, Durham, NC, USA, 9 Bonn University Hospital, Bonn, Germany, 10 Duke Clinical Research Institute, Durham, NC, USA Background: Switches in antiretroviral therapy (ART) to simplify and/or update regimens are increasingly common, with safety supported by randomized clinical trials. Switches in ARTs to limit drug interactions prior to initiating direct acting antivirals (DAA) for HCV are also common, although there are limited data to guide this practice and the risk of loss of HIV control is unknown. Furthermore, there are reports that ART switches may increase HCV treatment failure. Methods: This is the final analysis of a multicenter (N=9), observational clinical registry. The study population includes patients with HIV/HCV co-infection treated with ledipasvir/sofosbuvir. Cases (ART switch prior to HCV therapy) and controls (no ART switch prior to HCV therapy) were enrolled with a targeted 1:1 ratio and a planned total enrollment of 300 patients. The primary endpoint is HIV treatment failure defined by a combined endpoint of HIV virologic failure (confirmed HIV RNA >50 copies/mL >1 week apart), discontinuation of ART regimen, progression to AIDS, or death. Secondary endpoints include nephrotoxicity and sustained virologic response (SVR12), defined as an undetectable HCV RNA 12 weeks after DAA therapy. Analyses include use of Fischer’s exact for differences in proportions. Results: Total enrollment was 287 and 281 had evaluable data for the primary endpoint. The cohort is predominantly male (83%), with a mean age of 55 years, and 43% Black race. Patients who switched ARTs were more commonly on protease inhibitors and/or boosted-TDF regimens (Table). Overall, a total of 17 patients, 6% in each group, met the primary composite outcome of HIV treatment failure. Nephrotoxicity events (change from baseline creatinine of ≥0.4 mg/dL, decrease in creatinine clearance <50 mL/min or new >1+ proteinuria) occurred in 26% of patients and was not associated with ART switch or boosted-TDF during DAA therapy. Nephrotoxicity was more common in patients with lower baseline creatinine clearance or baseline proteinuria. Overall, 242 patients (14% no HCV RNA available after DAA therapy) had evaluable SVR12, which was 99%. Conclusion: In a real-world cohort of patients with HIV/HCV co-infection receiving ledipasvir/sofosbuvir, switches in ARTs were not associated with HIV treatment failure and did not prevent nephrotoxicity events. Nephrotoxicity was more common in patients with evidence of baseline renal dysfunction although it was not associated with discontinuation of therapy. HCV treatment success was independent of ART switch.

572 REAL-WORLD EFFECTIVENESS OF SOFOSBUVIR/VELPATASVIR FOR HEPATITIS C VIRUS INFECTION

Teresa Aldámiz-Echevarría 1 , Juan Berenguer 1 , Ángela Gil-Martín 2 , Javier García-Samaniego 3 , Laura Márquez 1 , José L. Calleja 4 , Luz Martin-Carbonero 3 , Ana Moreno 5 , Benjamín A. Polo Lorduy 6 , Pablo Ryan 7 , Luisa Consuelo García Buey 8 , María J. Devesa 9 , Inma Jarrin 10 , María J. Calvo 2 , Juan González-García 3 1 Hospital General Universitario Gregorio Marañón, Madrid, Spain, 2 Subdireccion General de Farmacia, Madrid, Spain, 3 La Paz University Hospital, Madrid, Spain, 4 Hospital Puerta de Hierro, Madrid, Spain, 5 Hospital Ramón y Cajal, Madrid, Spain, 6 Fundacion Jimenez Diaz, Madrid, Spain, 7 Hospital Universitario Infanta Leonor, Madrid, Spain, 8 Hospital Universitario de La Princesa, Madrid, Spain, 9 Hospital Universitario Clí¬nico San Carlos, Madrid, Spain, 10 Institute de Salud Carlos III, Majadahonda, Spain Background: Little is known about the real-world effectiveness of sofosbuvir and velpatasvir (SOF/VEL), a direct-acting antiviral agent (DAA) regimen with pan-genotypic activity. We evaluated the effectiveness and safety of SOF/VEL in a large prospective registry of individuals receiving DAAs for HCV. Methods: RUA-VHC (Madrid Registry of Use of DAA for HCV) is a prospective registry of HCV-monoinfected (MoP) and HIV/HCV-coinfected (CoP) individuals receiving all-oral DAAs in hospitals of the Madrid Regional Health Service. RUA-VHC was created in November 2014 (Hepatology 2017; 66:344). For this study, we selected patients with chronic hepatitis C who had received once- daily treatment with 1 tablet of the fixed-dose combination of SOF/VEL (400 mg/100 mg) for 12 wks. The patients were scheduled to finish treatment on or before 01/February/2019. Patients who were retreated after all-oral DAA therapy were excluded. We assessed sustained virologic response (SVR) at 12 wk by intention-to-treat (ITT) and by a modified intention-to-treat approach (m-ITT), in which non-virological failures for reasons other than discontinuation of treatment secondary to adverse events or death were not considered in the analysis. Results: A total of 1,003 patients (888 MoP/115 CoP) met the inclusion criteria. Median age was 55 y, 61.1%were men, 10.3%were previously treated, 19.7% had compensated cirrhosis, and 3.9% had decompensated cirrhosis. Genotype distribution was as follows: G1, 40.0%; G2, 11.2%; G3, 36.9%; G4, 7.6%. Other/ mixed/unknown genotypes accounted for 4.4%. Statistically significant differences were observed between MoP and CoP at baseline for age, gender, and genotype distribution. SVR rates overall were 95.4% by ITT and 97.9% by m-ITT (Table). The presence of HIV or genotype distribution did not influence response to treatment. The SVR rate was lower in patients with decompensated cirrhosis than in patients without cirrhosis both by ITT (87.2% vs 96.1%, P=0.008) and by m-ITT (91.9% vs 98.5%, P=0.003). Conclusion: In this large cohort of patients with hepatitis C, 12 wks of treatment with SOF/VEL led to SVR rates > 95%. Treatment with SOF/VEL was highly efficacious across all genotypes and in the presence of HIV. Response to treatment was significantly poorer in patients with decompensated cirrhosis than in patients without cirrhosis.

Poster Abstracts

CROI 2020 206