Sustained virologic response and changes in liver fibrosis parameters following 12-wk administration of generic sofosbuvir and daclatasvir in HIV/HCV-coinfected patients with HCV genotype 4 infection.

Novel direct-acting antiviral agents have shown great efficacy and tolerability in HCV-monoinfected patients. However, data are lacking regarding their efficacy and safety in HIV/HCV-genotype (GT) 4-coinfected patients. A single-centre, prospective study including HIV/HCV-GT 4-coinfected patients who were treated with sofosbuvir and daclatasvir (SOF/DCV) was conducted for 12 wk. Sustained virological response (SVR) at week 12 post-treatment (SVR12), adverse events (AEs) and changes in liver stiffness measurement (LSM) at SVR12 in comparison with baseline were evaluated. SVR12 was achieved in 46 of 50 patients (92%). No significant difference in SVR12 was noticed among patients who received antiretroviral therapy (ART) regimens compared with those who did not receive ART regimens or between those with insignificant fibrosis (<F2) and those with significant fibrosis (≥F2) (p=0.9 and p=0.3, respectively). AEs occurred in 45 (90%) patients. The most frequent AEs were fatigue, headache and nausea. No treatment-related serious AEs or deaths were reported. HIV control was not compromised. LSM, fibrosis 4 score and aspartate aminotransferase-to-platelet ratio index showed a significant decrease at SVR12 when compared with baseline (p=0.0004, p=0.0003 and p<0.0001, respectively). Logistic regression analysis showed no association between baseline variables and SVR12 while significant fibrosis (≥F2) was the only baseline variable that was significantly associated with improvement of LSM at SVR12. SOF/DCV achieved a high SVR12 and was well-tolerated in HIV/HCV-GT 4-coinfected patients.

Cordie A ，Elsharkawy A ，Abdel Alem S ，Meshaal S ，El Akel W ，Abdellatif Z ，Kamal W ，Al Askalany M ，Kamel S ，Abdel Aziz H ，Kandeel A ，Esmat G ... -  《-》

Daclatasvir and Sofosbuvir Versus Sofosbuvir and Ribavirin in Patients with Chronic Hepatitis C Coinfected with HIV: A Matching-adjusted Indirect Comparison.

Our aim was to compare the efficacy and tolerability of daclatasvir plus sofosbuvir (DCV+SOF) versus SOF plus ribavirin (SOF+R) in patients coinfected with HIV and hepatitis C virus (HCV). A systematic literature review of Phase III clinical trials identified 2 trials of SOF+R-PHOTON-1 (A Phase 3, Open-Label Study to Investigate the Efficacy and Safety of GS-7977 Plus Ribavirin in Chronic Genotype 1, 2 and 3 Hepatitis C Virus [HCV] and Human Immunodeficiency Virus [HIV] Co-Infected Subjects) and PHOTON-2 (A Phase 3, Open-Label Study to Investigate the Efficacy and Safety of Sofosbuvir Plus Ribavirin in Chronic Genotype 1, 2, 3 and 4 Hepatitis C Virus [HCV] and Human Immunodeficiency Virus [HIV] Co-Infected Subjects) suitable for comparison with the trial of DCV+SOF in patients coinfected with HIV and HCV-ALLY-2 (A Phase 3 Evaluation of Daclatasvir Plus Sofosbuvir in Treatment-naïve and Treatment-experienced Chronic Hepatitis C [Genotype 1, 2, 3, 4, 5, or 6] Subjects Coinfected With Human Immunodeficiency Virus [HIV]). Individual patient data from ALLY-2 were available; published summary data were extracted and pooled for the PHOTON trials. To adjust for cross-trial differences, ALLY-2 patients were subject to the inclusion and exclusion criteria reported in the PHOTON trials and were weighted to match all available summary baseline characteristics reported in both PHOTON trials. Sustained virologic response at week 12 post-treatment (SVR12) discontinuation due to adverse events (AEs) and rates of AEs were compared. The SVR12 rate was significantly higher among patients treated with DCV+SOF (n = 91) than among those treated with SOF+R (n = 455) both before (96.7% vs 84.6%; P = 0.002) and after (99.9% vs 84.6%; P < 0.001) adjusting for baseline characteristics. After adjustment, compared with patients treated with SOF+R, patients receiving DCV+SOF had a significantly lower rate of discontinuation due to AEs and significantly lower rates of the following specific AEs: cough, diarrhea, insomnia, nasopharyngitis, upper respiratory tract infection, and hemoglobin <10 g/dL. After adjustment for cross-trial differences in baseline characteristics, DCV+SOF was associated with a significantly higher SVR12 rate and lower rate of discontinuation due to AEs than SOF+R in patients coinfected with HIV and HCV.

Swallow E ，Song J ，Yuan Y ，Kalsekar A ，Kelley C ，Peeples M ，Mu F ，Ackerman P ，Signorovitch J ... -  《-》

Efficacy and safety of direct antiviral agents in a cohort of cirrhotic HCV/HIV-coinfected patients.

New direct-acting antiviral agents (DAAs) have shown great efficacy and tolerability in clinical trials and real-life cohorts. However, data are scarce regarding efficacy and safety in cirrhotic HCV/HIV-coinfected patients. A multicentre prospective analysis was performed in 13 Spanish hospitals, including all cirrhotic HCV/HIV-coinfected patients starting DAA combinations from January to December 2015. Sustained virological response 12 weeks after treatment (SVR12) was analysed. Withdrawal due to toxicity and/or hepatic decompensation and change in liver stiffness measurement (LSM) after HCV treatment were evaluated. Patients (n = 170) were mostly male (n = 125; 74.3%) with the following HCV genotype (Gt) distribution: Gt-1a, 68 (40%); Gt-1b, 21 (12.4%); Gt-4, 47 (27.6%); and Gt-3, 26 (15.3%). Baseline median LSM was 20.6 kPa (IQR 16.1-33.7) and log10 HCV-RNA 6.1 IU/mL (IQR 5.7-6.5). Most patients had a Child-Pugh class A score (n = 127; 74.7%) and 28 (16.5%) had prior hepatic decompensation. There were 89 (52.4%) pretreated patients with 40.4% (n = 36) of null responders. Preferred regimens were as follows: sofosbuvir/ledipasvir + ribavirin, 43 (25.3%) patients; sofosbuvir + simeprevir + ribavirin, 34 (20%); sofosbuvir/ledipasvir, 26 (15.3%) and sofosbuvir + daclatasvir + ribavirin, 25 (14.7%). Overall SVR12 was 92.9% (158/170), without differences between genotypes. Pretreated patients had lower SVR12 rates compared with naive (88.8% versus 97.5%; P = 0.026). Treatment failures were as follows: 7 (4.1%) relapses; 2 (1.2%) lost to follow-up; 1 (0.6%) toxicity-related discontinuation; 1 (0.6%) hepatic decompensation; and 1 (0.6%) viral breakthrough. On-treatment hepatic decompensation was recorded in four (2.4%) patients (encephalopathy and ascites, two each). Paired LSM in 33 patients showed a decrease of 5.6 kPa (95% CI 1.8-9.2; P = 0.004). In our cohort of cirrhotic HCV/HIV-coinfected patients, DAAs were highly safe and efficacious. Viral eradication was associated with a significant decrease in liver stiffness.

Navarro J ，Laguno M ，Vilchez HH ，Guardiola JM ，Carrion JA ，Force L ，Cairó M ，Cifuentes C ，Vilaró J ，Cucurull J ，Marco A ，Roget M ，Erice E ，Crespo M ，Catalano-Balear Study Group ... -  《-》

Daclatasvir plus sofosbuvir, with or without ribavirin, in real-world patients with HIV-HCV coinfection and advanced liver disease.

Rockstroh JK ，Ingiliz P ，Petersen J ，Peck-Radosavljevic M ，Welzel TM ，Van der Valk M ，Zhao Y ，Jimenez-Exposito MJ ，Zeuzem S ... -  《-》

High Efficacy and Safety of Flat-Dose Ribavirin Plus Sofosbuvir/Daclatasvir in Genotype 3 Cirrhotic Patients.

Pellicelli A ，Messina V ，Giannelli V ，Distefano M ，Palitti VP ，Vignally P ，Tarquini P ，Izzi A ，Moretti A ，Babudieri S ，Dell'Isola S ，Marignani M ，Scifo G ，Iovinella V ，Cariti G ，Pompili M ，Candilo FD ，Fontanella L ，Ettorre GM ，Vennarecci G ，Ippolito AM ，Barbarini G ... -  《-》