CROI 2018 Abstract eBook

Abstract eBook

Poster Abstracts

602 TREATMENT OF CHRONIC HEPATITIS C GT1,2,4 IN AFRICA: FINAL RESULTS OF ANRS TAC TRIAL Karine Lacombe 1 , Raoul Moh 2 , Corine Chazallon 3 , Babacar Sylla 4 , Maud Lemoine 5 , Charles Kouanfack 6 , Eric Tchoumi Leuwat 6 , Magloire Biwole Sida 6 , Fatoumata Fadiga 2 , Michèle Tagni-Sartre 6 , Viviane Marie Pierre Cisse 1 , Lawson- Ananissoh Laté Mawuli 2 , Pierre-Marie Girard 1 , Alain Attia 2 1 INSERM, Paris, France, 2 PAC-CI Program, Abidjan, Côte d’Ivoire, 3 INSERM, Bordeaux, France, 4 IMEA, Paris, France, 5 Imperial College London, London, UK, 6 IRD, Montpellier, France Background: With the advent of highly effective oral therapy for hepatitis C virus (HCV) infection and the recent World Health Organization commitment, HCV elimination has become a realistic goal. However, in sub-Saharan Africa the HCV epidemic remains a neglected issue and access to care and treatment is almost inexistent. The TAC ANRS 12311 trial is an international multicenter open label trial aimed to assess the feasibility, efficacy and safety of interferon-free therapy in HCV-infected patients in the sub-Saharan African setting. Methods: Adult patients with treatment-naïve chronic hepatitis C were recruited in Senegal, Côte d’Ivoire and Cameroon. Patients without decompensated cirrhosis received either a 12 week-combination of sofosbuvir plus weight-based ribavirin (SOF+RBV) if infected with genotype (GT) 2 or sofosbuvir/ ledipasvir (SOF+LDV) if infected with GT1 or 4. This trial included 120 participants in total (40 in each GT group). The primary endpoint was the sustained virological response (threshold of detectability 12 or 25 IU/mL), observed 12 weeks after the end of treatment (SVR12). Results: Of the 120 participants (male 54%, median age 58 years [IQR 49 –63], median plasma HCV-RNA 6.0 log IU/Ml [IQR 5.5 –6.6]), 36 were HIV-coinfected (median CD4: 624/mm 3 , IQR 442 - 844), all with plasma HIV-RNA<200 copies/ Ml. 14 (12%) patients had APRI score > 2 (F4) at baseline. All but one patient completed the 12-week treatment course, and the remaining one discontinued treatment for personal reason (travel abroad) but reached SVR12. No patient died or was lost to follow-up. 8 (7%) patients had an adverse event of grade 3 or 4 During treatment, 3 patients had a decrease in haemoglobin level between 70 and 94 g/L, one of whomwith a consequent reduction of RBV dosage. 37 cases of arterial hypertension were documented, 35 being pre-existing conditions and the 2 others unrelated to HCV drugs. HCV-RNA was measured at week 24 (documenting SVR12) in 119 patients, of whom 107 (90%) had undetectable viral load including 36 (90%) in GT-1, 36 (90%) in GT-2, and 35 (90%) in GT-4. 3 out of the 12 failing patients had an APRI score>2 (F4) at baseline. Conclusion: HCV treatment with SOF+RBV in GT-2 or SOF+LDV in GT-1 or GT-4 infected patients is feasible, safe and effective in sub-Saharan Africa including in HIV co-infected patients. With the growing access to HCV drugs at generic price worldwide, it is time to prompt scaling up of HCV treatment in Africa. 603 DAA IMPLEMENTATION RATE IN HIV/HCV PATIENTS IN SPAIN: 2 YEARS OF UNRESTRICTED ACCESS Antonio Rivero-Juárez 1 , Francisco Téllez 2 , Manuel Castaño 3 , Dolores Merino 4 , Nuria Espinosa 5 , Jesus Santos 3 , Juan Macías 6 , Maria Paniagua-Garcia 7 , Angel Zapata-Lopez 8 , Antonio Collado 9 , Amparo Gomez-Vidal 10 , Javier Perez Stachowski 11 , Leopoldo Muñoz-Medina 12 , Elisa Fernandez-Fuertes 13 , Antonio Rivero 1 1 Hospital Universitario Reina Sofia, Cordoba, Spain, 2 Hospital Universitario de Puerto Real, Cadiz, Spain, 3 Hospital Regional Universitario de Málaga, Málaga, Spain, 4 Hospital Juan Ramón Jiménez, Huelva, Spain, 5 Hospital Universitario Virgen del Rocio, Sevilla, Spain, 6 Hospital Universitario de Valme, Seville, Spain, 7 Hospital Universitario Virgen Macarena, Sevilla, Spain, 8 Hospital Universitario Jerez de la Frontera, Jerez de la Frontera, Spain, 9 Hospital Universitario Torrecardenas, Alemria, Spain, 10 Complejo Hospitalario de Jaén, Jaén, Spain, 11 Hospital Costa del Sol, Marbella, Spain, 12 Complejo Hospitalario Universitario de Granada, Granada, Spain, 13 Hospital de Poniente, El Ejido, Spain Background: In April 2015, the Spanish National Health System developed a strategic plan for unrestricted access to HCV direct-acting antiviral (DAAs) drug therapy. We evaluate the implementation of this strategy in HIV/HCV coinfected patients. Methods: The HERACLES cohort is a multicenter, prospective observational cohort initiated in April 2015, which includes HIV-infected patients with chronic HCV coinfection in follow-up at 19 reference centers for the care of

HIV-infected patients in Andalusia (southern Spain). Subjects were included in the cohort if they presented active chronic HCV coinfection and were not receiving HCV treatment. The treatment rate in our cohort was evaluated for 24 months after implementation of the Spanish HCV strategic plan. Multivariate analysis was performed to identify factors associated with a low DAA therapy implementation rate. Results: Of 15,556 HIV patients tested, 3,075 (19.7%) were chronically infected with HCV and were enrolled in the study. Of these patients, 68 (2.2%) were lost to follow-up after study inclusion. So, the target population consisted of 3007 patients. Of these, 86.7%were people who inject drugs (PWIDs), 58%were HCV G1, 16.4% HCV G3, 23.8% cirrhotic, and 30.8%were treatment-experienced patients. 1957 (65.1%) patients started DAA therapy. Rate of treatment according to liver fibrosis was: 90.1% in liver cirrhosis patients (647 of 718), 85.7% in F3 (662 of 772), 68.01% in F2 (319 of 469), 37.8% in F0-F1 (329 of 870). Of the 1483 patients with sustained virological response (SVR) who could be evaluated, 94.8% achieved it. During the study period, 158 (5.1%) patients died before receiving HCV therapy. At the end of study period, 892 patients with chronic HCV infection were pending to be treated. Thus, the prevalence of HCV RNA-positive in the whole HIV population at the end of the study period was 5.7%. In multivariate analysis, independent factors associated with a lower rate of treatment implementation were liver fibrosis stage of F0-F1 (OR = 0.073; 95% CI: 0.053-0.1) and use of opioid substitution therapy (OR = 0.594; 95% CI: 0.492-0.8). Conclusion: In the study period, a high number of HIV/HCV coinfected patients from our cohort received DAA therapy. In this difficult to treat cohort, with a high proportion of PWIDs and cirrhotic patients, the real-world SVR rate was 95%. Consequently, both these facts meant a significant reduction in HCV RNA- positive prevalence among HIV infected subjects. 604 MULTICENTER REGISTRY IN HIV/HCV CO-INFECTED PATIENTS INITIATING LEDIPASVIR/SOFOSBUVIR Kristen M. Marks 1 , Nwora L. Okeke 2 , Lawrence Park 3 , Cody A. Chastain 4 , Kimberly Workowski 5 , Chris Woods 2 , Kenneth E. Sherman 6 , Gregory K. Robbins 7 , Stefan Mauss 8 , Jürgen K. Rockstroh 9 , Susanna Naggie 3 1 Weill Cornell Medicine, New York, NY, USA, 2 Duke University, Durham, NC, USA, 3 Duke Clinical Research Institute, Durham, NC, USA, 4 Vanderbilt University, Nashville, TN, USA, 5 Emory University, Atlanta, GA, USA, 6 University of Cincinnati, Cincinnati, OH, USA, 7 Massachusetts General Hospital, Boston, MA, USA, 8 Heinrich Heine University Hospital, Düsseldorf, Germany, 9 Bonn University Hospital, Bonn, Germany Background: HCV treatment for HIV/HCV co-infected patients in the direct acting antiviral (DAA)-era is the same as for HCV-infected patients without HIV, but there is a need for attention to drug-interactions between antiretrovirals (ARVs) and DAAs. Switches in ARVs to limit drug interactions are common prior to initiating DAA, although there is limited data to guide this practice and the risk of loss of HIV control is unknown. Methods: This is the planned interim analysis of a multicenter (N=9), observational clinical registry. The study population includes patients with HIV/ HCV co-infection treated with ledipasvir/sofosbuvir. Cases (ARV switch prior to HCV therapy) and controls (no ARV switch prior to HCV therapy) are enrolled in a 1:1 ratio with a planned 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 ARV regimen, lost to follow-up, 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. Planned analyses include Fischer’s exact for differences in proportions. Results: To date 171 patients have enrolled and 146 had data entry completed and available for the analysis. The cohort is predominantly male (80%), with a mean age of 55.7 years, and 47% black race. The table summarizes the primary and secondary outcomes. Overall, 8 patients met the primary outcome. Nephrotoxicity events (change from baseline creatinine of ≥0.4 mg/dL, decrease in clearance of creatinine <50 mL/min or incident >1+ proteinuria) occurred in 30% of patients on tenofovir disoproxil fumarate (TDF)-containing regimens and 35% of patients on regimens without TDF. There was no difference in nephrotoxicity between cases and controls. Eleven patients were on boosted- ARV regimens containing TDF, one met nephrotoxicity criteria. The overall SVR for the 123 patients with follow-up during the SVR12 study windows was 100%.

Poster Abstracts

CROI 2018 222