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Background and Aim Elderly patients with hepatitis C virus (HCV) infection have worse interferon‐based treatment outcomes than young patients. Direct‐acting antiviral (DAA) regimens have enabled the treatment of previously difficult‐to‐cure populations. There are few studies that specifically assess DAA treatment outcomes in patients over 75 years of age. Methods Design: This was a cohort study. Setting: The setting was three Canadian HCV specialty sites. Participants: Patients aged 75 years and older and treated with DAA without interferon were enrolled. Measurements: Patient demographics, liver fibrosis by transient elastography, treatment regimen, and treatment outcome data were collected. Results The mean age of 78 patients in our analysis was 78.6 years (SD 3.5; range: 75–88 years). The most common genotype was 1b (35%). The most frequently utilized regimens included sofosbuvir‐velpatasvir (33%) and ledipasvir‐sofosbuvir (32%). Ribavirin was included for 17% of recipients. Sustained virological response (SVR) was achieved in 94% of patients (69% of those receiving ribavirin and 98% of patients on ribavirin‐free regimens). Ribavirin toxicity contributed to the lower SVR rates in ribavirin‐exposed patients. Ribavirin dosage was decreased in three patients and ultimately discontinued in two of these patients. All treatment was discontinued in another two patients. Conclusion Ribavirin‐free DAA therapy is safe and achieves SVR rates in older adults comparable to those described in the general population. RBV inclusion frequently results in complications, often leads to treatment modification or interruption, and does not improve SVR rates in those with advanced age., There is no literature evaluating the safety and efficacy of ribavirin in combination with hepatitis C virus (HCV) direct‐acting antiviral (DAA) for HCV treatment in the elderly. Our analysis provides a definite warning against the use of ribavirin in those over the age of 75 years. Our work also confirms the safety, excellent tolerance, and high efficacy of DAA therapy in the elderly population.

Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) is approved for treatment of HIV without known resistance to its components. Several studies have demonstrated efficacy of B/F/TAF in patients with nucleoside reverse transcriptase inhibitor (NRTI) resistance-associated mutations (RAMs), mainly identified by proviral DNA testing, but data on the efficacy of B/F/TAF in patients with NRTI RAMs identified in viraemic plasma are limited.We used a retrospective analysis of patients receiving B/F/TAF identified by searching electronic health records with eligibility confirmed by review of individual patient records. Patients included were ≥ 18 years, had 2019 International Antiviral Socitey-USA (IAS-USA) major RAMs affecting NRTIs detected in viraemic plasma prior to starting B/F/TAF and one or more HIV viral load (VL) after starting B/F/TAF.In all, 50 patients met the study criteria: mean age of 54 years, mean proximal CD4 count of 609 cells/μL, 64% male. A total of 46 were virologically suppressed ( 200 copies/mL) when B/F/TAF was initiated, two were treatment-naïve, one stopped prior antiretroviral therapy (ART) and one had a VL of 961 HIV-1 RNA copies/mL on ART. Twenty-nine had one NRTI RAM (24 were M184V/I), nine had two NRTI RAMs, three had three NRTI RAMs, four had four NRTI RAMs, two had five NRTI RAMs, one had six NRTI RAMs, one had seven RAMs and one had eight NRTI RAMs. At the last VL on B/F/TAF, a mean of 18.6 months after starting B/F/TAF, 49 out of 50 had VL 100 copies/mL and one had a VL of 208 copies/mL at 11 months but only filled 5 months of B/F/TAF.B/F/TAF was effective in maintaining HIV VL suppression in patients with previously documented NRTI RAMs without integrase resistance.

OBJECTIVES: Despite highly effective directly acting antiviral (DAA) therapy for hepatitis C virus (HCV), many patients do not receive treatment. We characterized the achievement of cascade of care milestones within 2 years of diagnosis among the Alberta population and evaluated variables associated with engagement at each stage. METHODS: All Albertans with a first-time positive HCV antibody between 2009 and 2014 were included in this retrospective study. We determined which patients received follow-up testing (HCV RNA and HCV genotype), referral to hepatitis specialty care, and antiviral prescription, and achieved SVR within 2 years of diagnosis. Factors associated with achieving cascade milestones were identified by multivariable logistic regression analysis. RESULTS: Of 6154 patients with HCV antibody and complete follow-up, 4238 (68.9%) had HCV RNA testing, 2360 (38.3%) had HCV genotyping, 2096 (34.1%) were assessed by a specialist, 711 (11.6%) were prescribed treatment and 207 (3.4%) achieved SVR within 2 years of diagnosis. Independent variables associated with reduced likelihood of achieving cascade milestones were Indigenous heritage (adjusted odds ratio (AOR) 0.53 (0.41–0.68) for HCV RNA testing), unstable housing (AOR 0.50 (0.32–0.79) for specialist assessment) and alcohol misuse (AOR 0.61 (0.38–0.99) for antiviral prescription). Men, older patients, patients with a higher income and patients with more advanced liver disease were more likely to achieve cascade of care milestones. CONCLUSION: At each stage of patient engagement, opportunities for improvement were identified. Understanding the local cascade of care and factors associated with achieving cascade milestones will help prioritize initiatives to facilitate access to DAA therapy in Alberta. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.17269/s41997-019-00234-z) contains supplementary material, which is available to authorized users.

Background TAF demonstrated noninferior efficacy to TDF with a superior bone and renal safety profile, in viremic chronic HBV (CHB) patients through week 96, and in virally suppressed patients switched from TDF to TAF at 48 weeks. The duration of prior TDF therapy may influence the degree and rate of recovery of bone and renal function following switch to TAF. Here, we evaluate the impact of prior TDF treatment duration on the safety profile of TAF in virally suppressed patients. Methods In a double-blind, randomized, multicenter, active-controlled, Phase 3 study, 488 CHB patients who were virologically suppressed on TDF for 1 year, and on TDF monotherapy for 6 months were randomized 1:1 to switch to TAF or continue TDF for 48 weeks. In patients originally randomized to receive TAF, renal, bone, and lipid parameters were categorically evaluated by the duration of prior TDF treatment: Results Of the 243 patients switched to TAF from TDF, 105 (43%) and 138 (57%) had received TDF for 50 years, 74% male, 80% Asian, median eGFRCG91 mL/min, 4% and 12% had osteoporosis at hip and spine, respectively. Similar changes in renal, bone, and lipid parameters following 48 weeks of TAF treatment were observed by TDF treatment duration. A comparable increase in median eGFRCG, decreases in tubular biomarkers (beta-2 microglobulin/creatinine ratio, retinol binding protein/creatinine ratio), increases in mean percent change in hip and spine BMD, and decreases in bone turnover markers (C-type collagen sequence, procollagen type 1 N-terminal propeptide) were observed among patients previously treated with Conclusions In virally suppressed patients on TDF a median of 4 years who switched to TAF treatment, improvements in bone and renal parameters and changes in fasting lipids were not impacted by prior duration of TDF use.

Summary This study evaluated 12‐week retreatment with sofosbuvir/velpatasvir/voxilaprevir in patients with chronic hepatitis C virus (HCV) infection who did not achieve sustained virologic response after previous treatment with a sofosbuvir‐ and velpatasvir‐containing regimen. All 31 patients maintained a sustained virologic response 12 weeks after the last sofosbuvir/velpatasvir/voxilaprevir dose.

Background Optimal treatment for patients with HCV genotype-3 infection and liver cirrhosis remains a medical priority. Daclatasvir+sofosbuvir and ribavirin is a recommended option for such patients, but clinical trial data are lacking for treatment >16 weeks. Methods This was a single-arm, Phase III study of daclatasvir+sofosbuvir+ribavirin for 24 weeks in patients with compensated cirrhosis and HCV genotype-3 infection. The primary end point was sustained virological response at post-treatment week 12 (SVR12); the primary objective was to demonstrate statistical superiority to historical SVR12 data for 12 weeks’ daclatasvir+sofosbuvir without ribavirin in genotype-3-infected patients with cirrhosis (95% CI lower bound >79.0%). Results A total of 78 patients were treated (54 treatment-naive, 24 treatment-experienced including 8 with prior sofosbuvir exposure). SVR12 was achieved by 87% (68/78; 95% CI 77.7, 93.7%) of patients in the primary analysis of central laboratory data. One additional patient achieved SVR12 by local testing resulting in an overall SVR12 rate of 88% (95% CI 79.2, 94.6%) and the lower bound of the 95% CI above the historical threshold. SVR12 rates were 93% (50/54) for treatment-naive and 79% (19/24) for treatment-experienced patients. Of the nine non-SVR12 patients, four were lost to follow-up, two relapsed (both sofosbuvir-experienced), two had end-of-treatment virological failure and one discontinued early. There were no unexpected safety signals; only one patient discontinued for an adverse event. Conclusions Daclatasvir+sofosbuvir+ribavirin for 24 weeks was well tolerated and efficacious in HCV genotype-3-infected patients with compensated cirrhosis, with SVR12 outcomes comparable to previously reported outcomes in patients treated with this regimen for 12–16 weeks.

Pre-exposure prophylaxis (PrEP) and non-occupational post-exposure prophylaxis (nPEP) are part of combination HIV prevention strategies that include behavioural interventions such as condoms and risk-reduction counselling. A 25-member panel was convened to develop Canadian guidelines for PrEP and nPEP, with the full guidelines recently published in the Canadian Medical Association Journal (CMAJ). This article provides a discussion beyond the guideline, highlighting areas of particular interest to infectious disease (ID) specialists and discusses the possible role of ID specialists as access to both PrEP and nPEP become more widely available across the country.

The efficacy and safety of an investigational combination of ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) plus sofosbuvir (SOF) ± ribavirin (RBV) in patients with HCV genotype 2 or 3 infection with or without cirrhosis was evaluated. Patients with HCV genotype 3 infection without cirrhosis were randomized to receive OBV/PTV/r + SOF ± RBV for 12 weeks; OBV/PTV/r + SOF + RBV was administered to genotype 3-infected patients with cirrhosis for 12 weeks and to genotype 2-infected patients without cirrhosis for either 6 or 8 weeks. Efficacy was assessed by sustained virologic response [HCV RNA

Background Data on persistence of NS5A resistance-associated substitutions (RASs) may have implications for resistance testing approaches and selection of initial and retreatment strategies. Methods Long-term persistence of NS5A RASs in HCV genotype (GT) 1 infected subjects ( n=76) who did not achieve sustained virological response after receiving ledipasvir (LDV) without sofosbuvir (SOF) and were subsequently enrolled in an ongoing 3-year follow-up registry study was investigated by population or deep sequencing. Results Of the 76 subjects enrolled, 67 and 9 subjects had GT1a and GT1b infection, respectively. At pretreatment, NS5A RASs were detected in 14% of subjects (11/76) by population sequencing, with three subjects having >1 RAS. All RASs that were detected at pretreatment persisted and were observed at the 96 week visit in the follow-up study (FU96). For the remaining subjects with no detectable RASs at pretreatment, RASs were detected in 98% (63/64) of subjects at virological failure in the parent study and persisted at detectable levels through FU96 in 86% of subjects by deep sequencing (1% cutoff). However, a decline in the quasispecies frequency of most RASs and the number of RASs per subject was observed over time. Phenotypic analysis demonstrated that the majority of NS5A RASs confer similar levels of resistance to LDV and daclatasvir. Conclusions The majority of NS5A RASs can persist at detectable levels for >96 weeks post-treatment in subjects who failed treatment with regimens containing an NS5A inhibitor without SOF, suggesting relatively high fitness of NS5A RASs even in the absence of drug pressure.

Background The Northern Alberta HIV Program (NAHP) provides care and support for about 2500 HIV positive individuals. Part of the program includes screening and therapy for co-morbidities such as hepatitis C virus (HCV) infection. This study aims to assess the occurrence of HCV co-infection among these patients, determine whether they had received treatment for HCV, and identify patients who are currently viremic so they can be linked to care. Methods NAHP patients from 2010 to 2019 were linked to their HCV antibody, RNA, and genotyping laboratory testing data from January 1, 2000 to December 31, 2019 as well as HCV medication dispensation data. Each patient’s current and previous state of HCV infection and treatment status was assessed. Chart reviews were conducted for patients presently HCV viremic to assess their HIV care and social determinants. Results Of the 2417 NAHP patients, 392 (16.2%) were identified as having been co-infected with HCV at some point between January 1, 2000 to December 31, 2019 and meeting the inclusion criteria. Overall, 198 (50.5%) of the HIV-HCV co-infected patients had received HCV treatment and 232 (59.2%) were no longer viremic at their most recent HCV RNA test. 99 (69.2%) of the 143 HCV viremic patients had a suppressed HIV infection suggesting they are active in their HIV care and good candidates for HCV treatment. Figure 1. 2417 patients in the Northern Alberta HIV Program were evaluated for the presence of an HIV- HCV co-infection. 404 patients were identified as having been HIV-HCV co-infected at some point between January 1, 2000 and December 31, 2019. Figure 2. 404 HIV-HCV co-infected patients from the Northern Alberta HIV Program were assessed for the occurrence of treatment as well as the current status of their HCV infection. 143 patients were found to currently have an active HIV-HCV co-infection. Table 2. Characteristics of HIV-HCV co-infected patients from the NAHP with an active HCV infection (n=143) Conclusion The NAHP has been successful in identifying and treating many of their HIV HCV co-infected patients, however, there remain patients with viremic HCV. Despite the availability of direct-acting antivirals (DAAs) in Alberta and many of these patients being successfully treated for HIV, a significant proportion of co-infected patients have not initiated HCV treatment The HIV treating physicians of these individuals will be notified and encouraged to assist in getting them linked to HCV care and treatment. Disclosures All Authors: No reported disclosures

Background and aims: Achieving sustained virological response (SVR; cure) in hepatitis C patients using a simple regimen is key to making elimination by 2030 possible. In the largest real-world analysis to date, the effectiveness of pangenotypic, panfibrotic, single-tablet, sofosbuvir/velpatasvir (SOF/VEL) once-daily for 12weeks was assessed in 12 clinical real-world cohorts from various geographical areas, settings and treatment practices. Factors affecting risk of not achieving SVR were assessed. Methods: Adults treated with SOF/VEL 400/100mg, without ribavirin, were included. All HCV patients reaching Week 12 or 24 post-treatment were assessed for SVR12/24. Factors associated with not achieving SVR12/24 for virological reasons were evaluated using logistic regression analysis. Results: Overall, 5552 patients were included: 13.3% treatment-experienced; 20.7% compensated cirrhotic; 30.2% genotype 1; 29.5% genotype 2; 32.9% genotype 3; 4.7% genotype 4; 3.7% HIV coinfection; 13.4% current/former intravenous drug use. Of the 5196 patients evaluated for effectiveness, 98.9% achieved SVR12/24. High SVR12/24 rates occurred in all genotypes including genotype 3 (98.3%; 1649/1677) and in those with compensated cirrhosis (97.9; 1055/1078). Only 55 patients did not achieve SVR12/24 due to a virological reason; the only factor statistically significantly associated with an increased risk of not achieving SVR12/24 was compensated cirrhosis (P=.002). Overall, 6% (332/5552) of patients did not achieve SVR12/24 for non-virological reasons (67% lost to follow-up; 26.5% early treatment discontinuation). Conclusions: In this large cohort, representative of clinical practice, a simple 12-week regimen of SOF/VEL without ribavirin resulted in high SVR12/24 rates in diverse patient populations, even among those with compensated cirrhosis.

[Background & Aims] Although off-label use of sofosbuvir-containing regimens occurs regularly in patients with hepatitis C virus (HCV) infection undergoing dialysis for severe renal impairment or end-stage renal disease (ESRD), these regimens are not licensed for this indication, and there is an absence of dosing recommendations in this population. This study evaluated the safety and efficacy of sofosbuvir/velpatasvir in patients with HCV infection with ESRD undergoing dialysis., [Methods] In this phase II, single-arm study, 59 patients with genotype 1–6 HCV infection with ESRD undergoing hemodialysis or peritoneal dialysis received open-label sofosbuvir/velpatasvir (400 mg/100 mg) once daily for 12 weeks. Patients were HCV treatment naive or treatment experienced without cirrhosis or with compensated cirrhosis. Patients previously treated with any HCV NS5A inhibitor were not eligible. The primary efficacy endpoint was the proportion of patients achieving sustained virologic response (SVR) 12 weeks after discontinuation of treatment (SVR12). The primary safety endpoint was the proportion of patients who discontinued study drug due to adverse events., [Results] Overall, 56 of 59 patients achieved SVR12 (95%; 95% CI 86–99%). Of the 3 patients who did not achieve SVR12, 2 patients had virologic relapse determined at post-treatment Week 4 (including 1 who prematurely discontinued study treatment), and 1 patient died from suicide after achieving SVR through post-treatment Week 4. The most common adverse events were headache (17%), fatigue (14%), nausea (14%), and vomiting (14%). Serious adverse events were reported for 11 patients (19%), and all were deemed to be unrelated to sofosbuvir/velpatasvir., [Conclusions] Treatment with sofosbuvir/velpatasvir for 12 weeks was safe and effective in patients with ESRD undergoing dialysis., [Lay summary] Sofosbuvir/velpatasvir is a combination direct-acting antiviral that is approved for treatment of patients with hepatitis C virus (HCV) infection. Despite the lack of dosing recommendations, sofosbuvir-containing regimens (including sofosbuvir/velpatasvir) are frequently used for HCV-infected patients undergoing dialysis. This study evaluated the safety and efficacy of sofosbuvir/velpatasvir for 12 weeks in patients with HCV infection who were undergoing dialysis. Treatment with sofosbuvir/velpatasvir was safe and well tolerated, resulting in a cure rate of 95% in patients with HCV infection and end-stage renal disease., Clinical Trial Number: NCT03036852.

Background Approved HCV treatments for patients on dialysis are associated with complexities including drug-drug interactions, baseline resistance testing and use of ribavirin. Despite higher concentrations of the primary circulating sofosbuvir (SOF) metabolite, GS-331007, in severe renal impairment, real-world cases demonstrated substantial use of SOF-based regimens in this population without safety concerns identified. This study evaluated the safety, efficacy, and pharmacokinetics (PK) of SOF/velpatasvir (VEL) for 12 weeks in patients with HCV infection on dialysis. Methods Treatment-naive or -experienced patients, of any genotype, with or without compensated cirrhosis undergoing hemodialysis or peritoneal dialysis, were enrolled to receive open-label SOF/VEL (400/100 mg) once daily for 12 weeks. The primary efficacy endpoint was a comparison of the SVR12 to a prespecified historic control rate of 83%. The primary safety endpoint was the proportion of patients who discontinued therapy due to adverse events (AEs). Secondary endpoints included safety, viral resistance and PK. Results 59 patients were enrolled at 21 sites in Canada, United Kingdom, Spain, Israel, Australia and New Zealand. The median age was 62 years (range 49–86), 59% were male, 53% white, 32% treatment experienced, 29% had cirrhosis. Most patients had HCV genotype 1 (42%), or 3 (27%). Most (92%) were on hemodialysis with a mean dialysis duration of 7.3 years. Treatment was well tolerated; no one discontinued therapy due to AEs. One patient was discontinued therapy on day 74 for non-compliance with 48% study medication adherence by pill count. Overall, 56/59 (95%) of patients achieved SVR12. Two (3%) had virologic relapse (one with non-adherence). One patient did not achieve SVR12 due to death from suicide after SVR4. Exposures were consistent with the Phase 1 renal impairment study. The most frequent AEs were headache, fatigue, nausea, and vomiting. Serious AEs occurred in 19% of patients, none was assessed as related to study drug. Conclusions Treatment with SOF/VEL for 12 weeks in patients with and without cirrhosis undergoing dialysis resulted in a 95% SVR12 rate. The regimen was safe and well-tolerated with no treatment-related discontinuations or treatment-related SAEs.

Introduction With the availability of direct-acting antivirals, Hepatitis C (HCV) is now considered a treatable disease. Patients who are co-infected with human immunodeficiency virus (HIV) and HCV represent an ideal patient population to treat for HCV, as (1) patients are routinely taking medication for HIV, and therefore would be able to complete HCV drug regimens, and (2) HIV infection has been shown to increase HCV disease progression. Objective We sought to determine the occurrence of HCV co-infection among HIV patients in our provincial cohort, determine whether they received treatment for HCV, and identify currently viremic patients who can be linked to care. Materials and methods HCV laboratory testing data (HCV antibody and HCV RNA) and HCV medication dispensation data was collected for all HIV positive patients. Current and previous HCV infection and treatment was assessed. Chart reviews were conducted for HCV viremic patients to assess their HIV care and social determinants. Results Of the 2417 HIV positive patients, 392 (16.2%) were identified as being co-infected with HCV. 198 (50.5%) of the HIV-HCV co-infected patients received HCV treatment and 232 (59.2%) were not viremic on the most recent HCV RNA test. 99 (69.2%) had a suppressed HIV infection suggesting they are active in their HIV care and good candidates for HCV treatment. Conclusion Despite the availability of direct-acting antivirals, many patients who are co-infected with HIV and HCV are not being treated for HCV. Routine surveillance of HIV-HCV co-infected patients could improve HCV treatment rates in a high-risk population.

BACKGROUND: Overuse of investigations, treatments, and procedures contribute to rising health care costs and may cause patient harm. In an attempt to promote higher-value health care, the Choosing Wisely Canada campaign has encouraged professional societies to develop statements that are directly actionable by their members. Currently, there are variations in infectious diseases practice that lead some patients to receive therapies and investigations that lack benefit and are potentially harmful. METHODS: The Association of Medical Microbiology and Infectious Disease Canada (AMMI) Canada established its Choosing Wisely Canada top five list of recommendations using the framework put forward by Choosing Wisely Canada. Following an electronic survey of its members regarding low-value practices within infectious diseases, AMMI Canada convened a working group that developed a list of draft recommendations and ranked the top five recommendations by consensus. This list was shared with the AMMI Canada membership electronically and during a national open forum. Following revisions based on feedback received, the AMMI Canada Executive Council and Guidelines Committee endorsed the final list, which was disseminated online. RESULTS: The top five declarative statements on infectious diseases practices that physicians and patients should question include: do not routinely prescribe intravenous forms of highly bioavailable antimicrobial agents for patients who can reliably take and absorb oral medications; do not prescribe alternative second-line antimicrobials to patients reporting nonsevere reactions to penicillin when beta-lactams are the recommended first-line therapy; do not routinely repeat CD4 measurements in patients with HIV infection with HIV-1 RNA suppression for >2 years and CD4 counts >500/μL, unless virological failure occurs or intercurrent opportunistic infection develops; do not routinely repeat radiologic imaging in patients with osteomyelitis demonstrating clinical improvement following adequate antimicrobial therapy; and do not prescribe aminoglycosides for synergy to patients with bacteremia or native valve infective endocarditis caused by Staphylococcus aureus. CONCLUSIONS: The Choosing Wisely Canada statements in infectious diseases endorsed by AMMI Canada represent a starting point to engage AMMI Canada members in broader discussions related to resource stewardship within infectious diseases practice and to take action.

BACKGROUND: Most recent major treatment guidelines recommend considering the patient profile and baseline prognostic factors (genotype, fibrosis level, treatment history) in the management of chronic hepatitis C virus (HCV) infections (CHC). There is, therefore, a need to better characterize clinician decision-making in real-life CHC management in Canada. AIMS: To describe the patient profile, prognostic factors and treatment strategies used in Canadian real-life CHC management. METHODS: Multicenter chart review of CHC patients diagnosed from 2005 to 2012. Patient data were extracted for a minimum of 2 years after CHC diagnosis. RESULTS: 250 patients were included with a mean (SD) follow-up after diagnosis of 5.9 (2.3) years. Table1 summarizes the patient/disease characteristics at CHC diagnosis and the mode of management. A majority of patients (70.4%) received some antiviral treatment, with a lower proportion of treated G1 patients vs. non-G1 patients (64% vs. 76.7%). The most common initial treatments were IFN/RBV dual therapy (68.4%) and NS3/4-containing IFN/RBV therapy (19.3%); Among non-G1 patients, 92.4% were treated with IFN/RBV dual therapy. SVR was achieved by 51.5% of patients (G1: 44.7%; non-G1: 62.2%), 19.3% relapsed and 11.1% were non-responders with initial treatment. The majority of treated patients (72.2%) experienced AEs, the most common ones being fatigue (33%), anemia (27.3%), insomnia (21.6%), neutropenia (18.8%). Two deaths were reported. CONCLUSIONS: Despite the majority of HCV patients having mild fibrosis and being treated, most frequently with dual IFN/RBV therapy, SVR rates were low prior to the all-oral DAA era, highlighting the need for more efficacious treatments and suggesting that recommendations to still use IFN are not justifiable. FUNDING AGENCIES: Abbvie corporation

Background. Hepatitis C virus (HCV) is currently classified into 8 genotypes and 86 subtypes. The objective of this study was to characterize novel HCV subtypes and to investigate the impact of subtypes on treatment outcome. Methods. Full-genome sequencing was performed on HCV plasma samples with, SCOPUS: ar.j, info:eu-repo/semantics/published

Since the introduction of suppressive antiretroviral therapy (ART), HIV has become a chronic disease, with infected people in high-income countries approaching similar life expectancy to the general population. As this population ages, an increasing number of people with HIV are living with age-, treatment-, and disease-related comorbidities. Lifestyle factors such as smoking, alcohol abuse, and substance misuse have a role in age-related comorbidity. Some degree of immune dysfunction is suggested by the presence of markers of immune activation/inflammation despite effective suppression of HIV replication. Cumulative exposure to some antiretroviral drugs contributes to HIV-associated comorbidities, with risk increasing with age. Specifically, tenofovir disoproxil fumarate (TDF), ritonavir-boosted atazanavir, and ritonavir-boosted lopinavir are associated with renal impairment, and TDF is known to cause loss of bone mineral density. Tenofovir alafenamide (TAF) was developed to improve on the safety profile of TDF, while maintaining its efficacy. TAF has better stability in plasma, and higher intracellular accumulation of tenofovir diphosphate in target cells, which has resulted in improved antiviral activity at lower doses with improved renal and bone safety. TAF has been studied extensively in randomized clinical trials and real-world studies. TAF-based regimens are recommended over TDF-containing regimens for the improved safety profile.

Sofosbuvir-velpatasvir is approved for the treatment of chronic hepatitis C virus (HCV) infection. In this single-arm, open-label, phase 3, deferred treatment study, we investigated the efficacy and safety of sofosbuvir-velpatasvir among patients randomized to the placebo group in the ASTRAL-1 study. Patients received sofosbuvir-velpatasvir (400/100 mg) once daily for 12 weeks. The primary efficacy endpoint was the proportion of patients with sustained virologic response 12 weeks after the end of therapy (SVR12). The primary safety endpoint was any adverse events (AEs) leading to the permanent discontinuation of study drug. Overall, 108/111 (97%, 95% confidence interval [CI], 92%-99%) achieved SVR12, and only one patient had virological failure. SVR12 was achieved by 61/63 (97%, 95%CI, 89%-100%) genotype 1 patients, 20/20 (100%; 95%CI, 83%-100%) with genotype 2, 19/19 (100%; 95%CI, 82%-100%) with genotype 4 and 8/9 (89%; 95% CI, 52%-100%) with genotype 6. All (19/19; 95%CI, 82-100) patients with cirrhosis and all (31/31, 95%CI, 89-100) with prior treatment experience achieved SVR12. The safety profile during treatment was similar to that observed in patients receiving placebo treatment. The most common AEs were headache, fatigue and nausea. One patient (1%) discontinued treatment due to an AE of gallbladder carcinoma, which was not considered related to treatment. Of five reported serious AEs, none were considered related to study drug. Sofosbuvir-velpatasvir for 12 weeks was effective and well tolerated among untreated and previously treated patients with HCV genotype 1, 2, 4 or 6 infection, including those with compensated cirrhosis (ClinicalTrials.gov NCT02346721).

A simple treatment regimen that is effective in a broad range of patients who are chronically infected with the hepatitis C virus (HCV) remains an unmet medical need.We conducted a phase 3, double-blind, placebo-controlled study involving untreated and previously treated patients with chronic HCV genotype 1, 2, 4, 5, or 6 infection, including those with compensated cirrhosis. Patients with HCV genotype 1, 2, 4, or 6 were randomly assigned in a 5:1 ratio to receive the nucleotide polymerase inhibitor sofosbuvir and the NS5A inhibitor velpatasvir in a once-daily, fixed-dose combination tablet or matching placebo for 12 weeks. Because of the low prevalence of genotype 5 in the study regions, patients with genotype 5 did not undergo randomization but were assigned to the sofosbuvir-velpatasvir group. The primary end point was a sustained virologic response at 12 weeks after the end of therapy.Of the 624 patients who received treatment with sofosbuvir-velpatasvir, 34% had HCV genotype 1a, 19% genotype 1b, 17% genotype 2, 19% genotype 4, 6% genotype 5, and 7% genotype 6. A total of 8% of patients were black, 19% had cirrhosis, and 32% had been previously treated for HCV. The rate of sustained virologic response among patients receiving sofosbuvir-velpatasvir was 99% (95% confidence interval, 98 to99). Two patients receiving sofosbuvir-velpatasvir, both with HCV genotype 1, had a virologic relapse. None of the 116 patients receiving placebo had a sustained virologic response. Serious adverse events were reported in 15 patients (2%) in the sofosbuvir-velpatasvir group and none in the placebo group.Once-daily sofosbuvir-velpatasvir for 12 weeks provided high rates of sustained virologic response among both previously treated and untreated patients infected with HCV genotype 1, 2, 4, 5, or 6, including those with compensated cirrhosis. (Funded by Gilead Sciences; ClinicalTrials.gov number, NCT02201940.).

Phase 3 trials of direct acting antiviral drugs (DAAs) for hepatitis C virus (HCV) excluded patients coinfected with human immunodeficiency virus (HIV). After approval, small trials were done in HIV-HCV coinfected patients. The status quo results in delayed access to DAAs for HIV coinfected patients, a group with more rapid progression of liver disease. This article reviews all approved DAAs and compares sustained virological response (SVR) rates in the HIV coinfected with those in the HCV monoinfected treated with the same regimen for the same HCV genotype. SVR rates in HCV genotype 1 to 4 are virtually identical in the HIV co-infected as in the HCV monoinfected, regardless of whether the regimens contain interferon. Because HIV coinfection does not affect SVR rates or toxicity with DAA-containing therapy, excluding HIV coinfected patients from clinical trials of DAA-containing anti-HCV therapy is discriminatory and unnecessary. Rather, HIV coinfection is one of many comorbidities that occur in some patients with HCV infection.

AIMS: The advent of direct acting antivirals is expected to improve the management of Chronic Hepatitis – C (c-HCV). METHODS: MOSAIC an observational study conducted in 30 countries describes the profile of c-HCV patients and the impact of Interferon (IFN) treatment on Patient Reported Outcomes and outpatient consultations (Table). Consecutive c-HCV patients initiated on IFN-based treatment were followed for 48 weeks. RESULTS: Of 346 invited patients 279 participated; (189 treatment-naïve and 90 treatment-experienced). IFN-treatment was initiated for 55 (20%): DAA+peg-IFN+RBV: 5, peg-IFN+RBV: 19, IFN+RBV: 1, other: 30. Main reasons for not initiating IFN for physicians were: waiting for new options (32%, 13%); tolerability (15%, 7%); contraindications (9%, NA); costs (7%, 1%) and for patients inconvenience (2%); impact on social/family life and work (9%). Demographic characteristics {Mean (SD) [Range]} of the 55 treated patients: Age: 52.1 (10.39) [31–74] yrs; Duration since HCV diagnosis: 10.8 (10.1) [0 – 46] yrs; and 69.1% male. Baseline cirrhosis status was: minimal/no fibrosis: 20(36.4%), bridging fibrosis: 16(29.1%), cirrhosis: 11(20.0%), portal fibrosis: 4(7.3%) and NA: 4(7.3%). Genotype was G1: 34(61.8%), G3: 11(20.0%), G2: 6(10.9%), G6: 2(3.6%) and n = 1 (1.9%) each for G4, G5. Baseline HCV-RNA level was 800,000 IU/ml: 26(47%) x IU/mL, positive by qualitative assay: 5 (9%), NA: 4(7%). Employment decreased from 46% to 33%. Outpatient consultation during treatment was none: 64%; 1: 11%. >=4: 20%. CONCLUSIONS: IFN use in c-HCV patients in MOSAIC is low. Patients treated with IFN-containing regimens experience a substantial negative impact on QoL and productivity. Anticipated availability of new IFN-free regimens is the main reason for not initiating treatment with IFN. FUNDING AGENCIES: Abbvie Corporation

We present a case of Mycobacterium chimaera infection presenting with aortic dissection and pseudoaneuysm in a 22-year-old man with a past history of aortic valve replacement. Clinicians should consider M. chimaera infection in those presenting with aortic dissection as a late complication of cardiovascular surgery.

KEY POINTS New HIV infections occur every year in Canada,[1][1] highlighting the need for integrated prevention programs. Pre-exposure prophylaxis (PrEP) and nonoccupational postexposure prophylaxis (nPEP) are two important strategies for preventing HIV that should be considered standard of care and

Simplified regimens with reduced pill burden and fewer side-effects are desirable for people living with HIV. We investigated the efficacy and safety of switching to a single-tablet regimen of darunavir, cobicistat, emtricitabine, and tenofovir alafenamide versus continuing a regimen of boosted protease inhibitor, emtricitabine, and tenofovir disoproxil fumarate.EMERALD was a phase-3, randomised, active-controlled, open-label, international, multicentre trial, done at 106 sites across nine countries in North America and Europe. HIV-1-infected adults were eligible to participate if they were treatment-experienced and virologically suppressed (viral load50 copies per mL for ≥2 months; one viral load of 50-200 copies per mL was allowed within 12 months before screening), and patients with a history of virological failure on non-darunavir regimens were allowed. Randomisation was by computer-generated interactive web-response system and stratified by boosted protease inhibitor use at baseline. Patients were randomly assigned (2:1) to switch to the open-label study regimen or continue the control regimen. The study regimen consisted of a fixed-dose tablet containing darunavir 800 mg, cobicistat 150 mg, emtricitabine 200 mg, and tenofovir alafenamide 10 mg, which was taken once per day for 48 weeks. The primary outcome was the proportion of participants with virological rebound (confirmed viral load ≥50 copies per mL or premature discontinuations, with last viral load ≥50 copies per mL) cumulative through week 48; we tested non-inferiority (4% margin) of the study regimen versus the control regimen in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT02269917.The study began on April 1, 2015, and the cutoff date for the week 48 primary analysis was Feb 24, 2017. Of 1141 patients (763 in the study group and 378 in the control group), 664 (58%) had previously received five or more antiretrovirals, including screening antiretrovirals, and 169 (15%) had previous virological failure on a non-darunavir regimen. The study regimen was non-inferior to the control for virological rebound cumulative through week 48 (19 [2·5%] of 763 patients in the study group vs eight (2·1%) of 378 patients in the control group; difference 0·4%, 95% CI -1·5 to 2·2; p0·0001). No resistance to any study drug was observed. Numbers of discontinuations related to adverse events (11 [1%] of 763 patients in the study group vs four [1%] of 378 patients in the control group) and grade 3-4 adverse events (52 [7%] patients vs 31 [8%] patients) were similar between the two groups. There was a small non-clinically relevant but statistically significant (0·2 [SD 1·1] vs 0·1 [1·1], p=0.010) difference between the two groups in change from baseline in total cholesterol to HDL-cholesterol ratio. Only one serious adverse event (pancreatitis in the study group) was deemed as possibly related to the study regimen.Our findings show the safety and efficacy of single-tablet darunavir, cobicistat, emtricitabine, and tenofovir alafenamide as a potential switch option for the treatment of HIV-1 infection in adults with viral suppression.Janssen.