Early emergence of opportunistic infections after starting direct‐acting antiviral drugs in HIV/HCV‐coinfected patients

HEPAVIR, GEHEP and RIS‐HEP07 study groups.Varicella‐zoster virus and hepatitis B virus reactivations have been reported after starting interferon‐free direct‐acting antiviral agent (DAA ) combinations. HIV /HCV ‐coinfected patients could be a high‐risk group for the reactivation of latent infections. Because of these, we report the occurrence of severe infections after starting DAA regimens in HIV /HCV ‐coinfected patients. Individuals included in the HEPAVIR ‐DAA (NCT 02057003) cohort were selected if they had received all‐oral DAA combinations. A retrospective review of clinical events registered between the start of DAA s and 12 months after SVR 12 was carried out. Overall, 38 (4.5%) of 848 patients presented infections. The incidence (95% confidence interval) of infections was 4.6 (3.3‐6.3) cases per 100 person‐years. The median (Q1‐Q3) time to the infection since baseline was 23 (7.3‐33) weeks. Five (13%) of the patients with infections died; four of them had cirrhosis. The frequency of previous AIDS was 21 (54%) for patients with infections and 324 (40%) for those without infections (P = 0.084). The median (Q1‐Q3) nadir CD 4 cell count of individuals with and without infections was 75 (53‐178) and 144 (67‐255) cells/μL, respectively (P = 0.047). Immunodepression‐associated infections were observed in 9 (1.1%) patients. All of them had suppressed HIV replication with antiretroviral therapy. In conclusion, severe infections are relatively common among HIV /HCV ‐coinfected patients receiving all‐oral DAA combinations. Some unusual reactivations of latent infections in patients with suppressed HIV replication seem to be temporally linked with DAA use.This study was partly supported by grants from the Ministerio de Economía, Industria y competitividad, Instituto de Salud Carlos III (grant no: PI15/01607; grant no: PI16/01443) and from the Grupo para el Estudio de las Hepatitis Víricas (GEHEP) from SEIMC (grant no: GEHEP011). J.M. is the recipient of a grant from the Servicio Andaluz de Salud de la Junta de Andalucía (grant number B‐0037). J.A.P. is the recipient of an intensification grant from the Instituto de Salud Carlos III (grant number Programa‐I3SNS). This work has been partially funded by the Spanish AIDS Research Network RD16/0025/0010‐ISCIII‐FEDER.Peer reviewe

Predictors of hepatitis C treatment failure after using direct-acting antivirals in people living with human immunodeficiency virus

Background: Little is known about the influence of ongoing barriers to care in the persistence of hepatitis C virus (HCV) viremia after treatment with direct-acting antivirals (DAAs) among people living with human immunodeficiency virus (PLWH). Methods: We conducted a retrospective cohort analysis of PLWH treated through the standard of care in 3 Western countries, to investigate the predictors of HCV treatment failure (clinical or virologic), defined as having a detectable serum HCV ribonucleic acid within 12 weeks after DAA discontinuation. In addition to HCV and liver-related predictors, we collected data on ongoing illicit drug use, alcohol abuse, mental illness, and unstable housing. Logistic regression analyses were used to identify predictors of HCV treatment failure. Results: Between January 2014 and December 2017, 784 PLWH were treated with DAA, 7% (n = 55) of whom failed HCV therapy: 50.9% (n = 28) had a clinical failure (discontinued DAA therapy prematurely, died, or were lost to follow-up), 47.3% (n = 26) had an HCV virologic failure, and 1 (1.8%) was reinfected with HCV. Ongoing drug use (odds ratio [OR] = 2.60) and mental illness (OR = 2.85) were independent predictors of any HCV treatment failure. Having both present explained 20% of the risk of any HCV treatment failure due to their interaction (OR = 7.47; P < .0001). Predictors of HCV virologic failure were ongoing illicit drug use (OR = 2.75) and advanced liver fibrosis (OR = 2.29). Conclusions: People living with human immunodeficiency virus with ongoing illicit drug use, mental illness, and advanced liver fibrosis might benefit from enhanced DAA treatment strategies to reduce the risk of HCV treatment failure

Week 4 response predicts sustained virological response to all-oral direct-acting antiviral-based therapy in cirrhotic patients with hepatitis C virus genotype 3 infection

Objective: The aim of this study was to determine the predictive capacity of response at treatment week (TW) 4 for the achievement of sustained virological response 12 weeks after the scheduled end of therapy date (SVR12) to treatment against hepatitis C virus (HCV) genotype 3 (GT3) infection with all-oral direct-acting antiviral (DAA) -based regimens.Patients and methods: From a prospective multicohort study, HCV GT3-infected patients who completed a course of currently recommended DAA-based therapy at 33 Spanish hospitals and who had reached the SVR12 evaluation time-point were selected. TW4 HCV-RNA levels were categorized as target-notdetected (TND), below the lower limit of quantification (LLOQTD) and >= LLOQ.Results: A total of 123 patients were included, 86 (70%) received sofosbuvir/ daclatasvir +/- ribavirin, 27 (22%) received sofosbuvir/ ledipasvir/ ribavirin and 10 (8.1%) received sofosbuvir/ ribavirin, respectively. In all, 114 (92.7%) of the 123 patients presented SVR12 in an on-treatment approach, but nine (7.3%) patients relapsed, all of them had presented cirrhosis at baseline. In those who achieved TND, LLOQTD and >= LLOQ, SVR12 was observed in 81/83 (98%; 95% CI 91.5%-99.7%), 24/28 (85.7%; 95% CI 67.3%-96%) and 9/12 (75%; 95% CI 42.8%-94.5%), respectively; p(linear association) 0.001. Corresponding numbers for subjects with cirrhosis were: 52/54 (96.3%; 95% CI 87.3%-95.5%), 14/ 18 (77.8%; 95% CI 52.4%-93.6%) and 7/10 (70%; 95% CI 34.8%-93.3%); p 0.004.Conclusions: TW4-response indicates the probability of achieving SVR12 to currently used DAA-based therapy in HCV genotype 3-infected individuals with cirrhosis. This finding may be useful to tailor treatment strategy in this setting. (C) 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved

Week 4 response predicts sustained virological response to all-oral direct-acting antiviral-based therapy in cirrhotic patients with hepatitis C virus genotype 3 infection.

The aim of this study was to determine the predictive capacity of response at treatment week (TW) 4 for the achievement of sustained virological response 12 weeks after the scheduled end of therapy date (SVR12) to treatment against hepatitis C virus (HCV) genotype 3 (GT3) infection with all-oral direct-acting antiviral (DAA) -based regimens. From a prospective multicohort study, HCV GT3-infected patients who completed a course of currently recommended DAA-based therapy at 33 Spanish hospitals and who had reached the SVR12 evaluation time-point were selected. TW4 HCV-RNA levels were categorized as target-not-detected (TND), below the lower limit of quantification (LLOQTD) and ≥LLOQ. A total of 123 patients were included, 86 (70%) received sofosbuvir/ daclatasvir±ribavirin, 27 (22%) received sofosbuvir/ ledipasvir/ ribavirin and 10 (8.1%) received sofosbuvir/ ribavirin, respectively. In all, 114 (92.7%) of the 123 patients presented SVR12 in an on-treatment approach, but nine (7.3%) patients relapsed, all of them had presented cirrhosis at baseline. In those who achieved TND, LLOQTD and ≥LLOQ, SVR12 was observed in 81/83 (98%; 95% CI 91.5%-99.7%), 24/28 (85.7%; 95% CI 67.3%-96%) and 9/12 (75%; 95% CI 42.8%-94.5%), respectively; p(linear association) 0.001. Corresponding numbers for subjects with cirrhosis were: 52/54 (96.3%; 95% CI 87.3%-95.5%), 14/18 (77.8%; 95% CI 52.4%-93.6%) and 7/10 (70%; 95% CI 34.8%-93.3%); p 0.004. TW4-response indicates the probability of achieving SVR12 to currently used DAA-based therapy in HCV genotype 3-infected individuals with cirrhosis. This finding may be useful to tailor treatment strategy in this setting