Direct-acting Antivirals Initiation Research Articles

Minimal clinically important differences in health-related quality of life after treatment with direct-acting antivirals for chronic hepatitis C: ANRS CO22 HEPATHER cohort (PROQOL-HCV).

Patient Reported Outcomes Quality of Life survey for HCV (PROQOL-HCV) is a specific tool developed to assess health-related quality of life (HRQoL) in patients with chronic hepatitis C receiving direct-acting antivirals (DAA). Thresholds for clinically meaningful changes in PROQOL-HCV scores should be documented to improve the tool's use in clinical practice. This study aimed to estimate the minimal clinically important differences (MCIDs) in PROQOL-HCV scores before and after HCV cure by DAA among participants in the prospective cohort ANRS-CO22 HEPATHER. Data from 460 chronic HCV patients were collected at DAA initiation (baseline) and 24weeks after treatment end. MCIDs were estimated for the six HRQoL dimensions (Physical Health (PH), Emotional Health (EH), Future Uncertainty (FU), Intimate Relationships (IR), Social Health (SH), and Cognitive Functioning (CF)) using two approaches: anchor-based and score distribution-based. Each MCID was estimated for improvement/deterioration both globally and separately for patients with a baseline PRQoL-HCV score ≤ 50 (group1) and patients with a baseline PRQoL-HCV score > 50 (group2). The pooled MCIDs for improvement/deterioration globally, in group1, and in group2, respectively, were as follows: 8.8/-7.6, 9.7/-9.5, and 6.0/-6.9 for PH; 7.1/-4.6, 7.7/-9.6, and 6.6/-6.7 for EH; 6.7/-6.7, 8.2/-8.2, and 6.0/-6.0 for FU; 7.0/-7.0, 5.4/-5.4, and 6.2/-6.2 for IR; 7.7/-7.7, 8.6/-8.6, and 6.5/-6.5 for SH; 7.3/-5.6, 9.1/-8.0, and 6.5/-6.3 for CF. The overall MCID for the PROQOL-HCV scores ranged from 6.7 to 8.8 for improvement and from -7.7 to -4.6 for deterioration. The effect of DAA on PROQOL-HCV scores seemed particularly beneficial for patients with lower baseline scores. This subgroup could be motivated to take DAA if they are informed of the benefits for their HRQoL.

Hepatitis C Virus-Related One-Year Hepatocellular Carcinoma Recurrence After Directly Acting Antivirals: A Randomized Controlled Trial.

Available data on hepatocellular carcinoma (HCC) recurrence after direct-acting antivirals (DAAs) treatment for hepatitis C virus (HCV) are conflicting. No randomized trials were done. This study aims to compare the 1-year HCC recurrence rates in patients who received DAAs after tumor ablation versus those who postponed HCV treatment for 1year. Included patients were randomized after complete HCC ablation into two groups: a postponed DAAs group for whom DAAs initiation was postponed for 12months and a DAAs group who were given sofosbuvir/velpatasvir. Patients were followed for 1year. Eighty-four HCV patients with a mean age of 56.35 ± 8.12years were included; 78.57% of them were males. The number of lesions per patient ranged from 1 to 3 lesions, and the size of the largest lesion ranged from 1.5 to 5cm. There were no statistically significant differences between both groups regarding baseline characteristics. In the DAAs group (43 patients), 11 patients had HCC recurrence, while 25 patients in the postponed DAAs group (41 patients) had HCC recurrence. Using Kaplan-Meier analysis, the 1-year recurrence-free survival (RFS) was significantly higher in the DAAs group (72.2% vs. 38%, P = 0.001). On multivariate analysis, both higher albumin levels (HR 0.147, 95% CI 0.066-0.329) and receiving DAAs (HR 0.358, 95% CI 0.176-0.730) 1year after ablation were associated with significantly lower recurrence. Direct-acting antiviral usage after complete hepatocellular carcinoma ablation significantly decreases the 1-year HCC recurrence rates, but the risk of recurrence is still not eliminated.The study registration number on clinicaltrials.gov : NCT04653818 (initial release on 28/11/2020).

The Association between Urinary Alcohol Metabolites on Hepatitis C Treatment and Response

Background: Direct-acting antiviral (DAA) medications for the treatment of chronic hepatitis C virus (HCV) infection has achieved higher rates of sustained virologic response (SVR) with shorter treatment durations and no alcohol abstinence prerequisite. Previous therapies required alcohol abstinence for at least 6 months. Methods: Our retrospective cohort study in Veterans with chronic HCV infection presenting for care at the Joseph Maxwell Cleland Atlanta VA medical center (AVAMC) between 1/1/2015 – 11/29/2017 examined the relationship between alcohol use, DAA initiation, and SVR. Results: The cohort included 1763 people that were mostly males (97%) with a mean age of 63 years and 70% Black. In multivariate analysis, the odds of receiving DAA were 0.7 (95% CI: 0.674, 0.9; p=0.0013) in those with “detectable” alcohol metabolites compared with those who had “undetectable” alcohol metabolites. The odds of achieving SVR were 0.7 (95% CI: 0.5, 1.0; p=0.0525) in those with “detectable” alcohol metabolites. Overall, 86% of patients who received DAA therapy achieved SVR. Conclusions: Alcohol use categorized using urine alcohol metabolite testing, during the study period was associated with a significantly lower odds of receiving DAA therapy but had no statistical significance on the odds of achieving SVR. While patients with chronic hepatitis C should be counseled on the risks of alcohol use, it is not associated with lower likelihood of achieving SVR and should not preclude the initiation of DAA therapy

CD4+ T-cell recovery in HIV/hepatitis C co-infected patients following successful hepatitis C treatment.

Hepatitis C virus (HCV)/HIV co-infection has been identified as a risk for impaired CD4+ T-cell recovery, possibly mediated by HCV-induced liver fibrosis and/or immune activation. As HCV direct-acting antivirals (DAAs) may partially reverse liver fibrosis and immune activation, sustained HCV virological response (SVR) may lead to improved CD4 recovery. We explored the effect of HCV DAA-induced SVR on CD4 recovery among patients living with both HCV and HIV, including those with poor CD4 recovery on antiretroviral therapy (immunological non-responders [INRs]). Subjects aged ≥18 years living with both HIV and HCV who achieved SVR with DAA were included. Pre-DAA CD4 counts were included only after sustained HIV viral suppression and HIV viral suppression was maintained for the duration of the study. Segmented regression of interrupted time series analysis was used to evaluate changes in median CD4 count in the pre-DAA period (-36 months) versus the post-DAA period (+36 months). In total, 156 patients were included. In the full cohort, median CD4 counts increased by 15% (p = 0.002) in the 6-month period following DAA initiation, whereafter CD4 counts decreased by 2.7% per 6-month period (p = 0.004). Among the 13 INRs, there was no immediate effect on median CD4 in the first 6 months after DAA initiation, whereafter there was a sustained CD4 increase (4.1% per 6-month time interval [p = 0.02]). In total, 54% of INRs recorded a post-DAA CD4 count of >350 cells/mm3. Successful DAA therapy induced a modest immediate CD4 immunological reconstitution among this cohort of patients living with both HIV and HCV, although this effect waned with time. By contrast, among INRs, achieving HCV SVR led to slower but sustained CD4 count recovery.

2499. What Are We Waiting for? Chronic Hepatitis C Treatment Initiation During Inpatient Admission

Abstract Background Chronic hepatitis C virus (HCV) infection is highly prevalent among people who inject drugs. This vulnerable population experiences many barriers to engaging with the healthcare system. Evaluating and treating HCV during a hospital stay can be an opportunity to cure and prevent adverse HCV complications in a population that can be difficult to reach in an outpatient setting. Methods This was a retrospective review of treatment outcomes of patients who started on treatment for HCV infection with direct acting antivirals (DAAs) while hospitalized at an academic medical center between January 2022 and January 2023. DAAs were dispensed by outpatient pharmacies and brought into the hospital for patient use. Various teams were involved in the treatment of these patients and level of support varied between groups, ranging from full social services and pharmacy support to follow-up clinic visits only. Data collected included demographics, insurance type, injection drug use, housing status, DAA agents used, treatment duration and completion status, and sustained virological response (SVR) 12 or more weeks post-treatment. Results A total of 17 patients began treatment with DAAs while hospitalized. Sixteen (94%) were treated with glecaprevir-pibrentasvir for 8 weeks, while 1 (6%) received sofosbuvir-velpatasvir for 12 weeks. Sixteen (94%) reported using injection drugs and 12 (71%) reported unstable housing. All patients had government-managed health insurance, with 16 having Medicaid. Twelve (71%) patients completed treatment: 9 of 12 patients who completed treatment attained SVR12 and 3 were lost to follow up after treatment completion. Of the 5 patients who did not finish treatment, 2 attained SVR12 despite incomplete therapy, 1 is not yet due for SVR12, and 2 were lost to follow up. Conclusion In a vulnerable population with barriers to outpatient care, in-hospital evaluation and DAA initiation is a valuable opportunity to cure. Further evaluation is needed to optimize and implement strategies for inpatient HCV treatment initiation. Disclosures All Authors: No reported disclosures

Real-world Experiences in the Transplantation of Hepatitis C-NAAT-positive Organs.

Hepatitis C virus (HCV) nucleic acid amplification test (NAAT)-positive donors have increased the organ pool. Direct-acting antivirals (DAAs) have led to high rates of treatment success and sustained virologic response (SVR) in recipients with donor-derived HCV infection without significant adverse effects, although variability remains in the timing and duration of antivirals. This retrospective study analyzed all adult HCV-NAAT-negative transplant recipients who received an organ from HCV-NAAT-positive donors from November 24, 2018, to March 31, 2022, at Duke University Medical Center with protocolized delay of DAA initiation until after hospital discharge, with at least 180-d follow-up on all patients. Transplant and HCV-related outcomes were analyzed. Two hundred eleven transplants (111 kidneys, 41 livers, 34 hearts, and 25 lungs) were performed from HCV-NAAT-positive donors to HCV-NAAT-negative recipients. Ninety percent of recipients became viremic within 7 d posttransplant. Ninety-nine percent of recipients were initiated on pangenotypic DAAs in the outpatient setting a median of 52 d posttransplant, most commonly with 12-wk courses of sofosbuvir-velpatasvir (lungs) and glecaprevir-pibrentasvir (heart, kidney, and liver). Ninety-seven percent of recipients had SVR after a first-line DAA; all ultimately achieved SVR at 12 wk after subsequent treatment courses. The median peak HCV RNA for all organ systems was 2 436 512 IU/mL; the median time from antiviral to undetectable RNA was 48 d, although differences were noted between organ groups. No patient deaths or graft losses were directly attributable to HCV infection. One hundred percent of transplant recipients of HCV-NAAT-positive organs ultimately developed SVR without significant adverse effects when HCV antivirals were initiated in the outpatient setting after transplant hospitalization, suggesting that this real-world treatment pathway is a viable option.

Assessing the impact of direct-acting antivirals on hepatitis C complications: a systematic review and meta-analysis.

Direct-acting antivirals (DAA) have become the treatment of choice for hepatitis C. Nevertheless, efficacy of DAA in preventing hepatitis C complications remains uncertain. We evaluated the impact of DAA on hepatocellular carcinoma (HCC) occurrence and recurrence, all-cause mortality, liver decompensation and liver transplantation as compared to non-DAA treated hepatitis C and the association to baseline liver status. A systematic search for articles from March 1993 to March 2022 was conducted using three electronic databases. Randomized, case-control and cohort studies with comparison to non-DAA treatment and reporting at least one outcome were included. Meta-analysis and sub-group meta-analysis based on baseline liver status were performed. Of 1497 articles retrieved, 19 studies were included, comprising of 266,310 patients (56.07% male). DAA reduced HCC occurrence significantly in non-cirrhosis (RR 0.80, 95% CI 0.69-0.92) and cirrhosis (RR 0.39, 95% CI 0.24-0.64) but not in decompensated cirrhosis. DAA treatment lowered HCC recurrence (RR 0.71, 95% CI 0.55-0.92) especially in patients with baseline HCC and waiting for liver transplant. DAA also reduced all-cause mortality (RR 0.43, 95% CI 0.23-0.78) and liver decompensation (RR 0.52, 95% CI 0.33-0.83) significantly. However, DAA did not prevent liver transplantation. The study highlighted the importance of early DAA initiation in hepatitis C treatment for benefits beyond sustained virological response. DAA therapy prevented HCC particularly in non-cirrhosis and compensated cirrhosis groups indicating benefits in preventing further worsening of liver status. Starting DAA early also reduced HCC recurrence, liver decompensation, and all-cause mortality.

Inpatient Hepatitis C Treatment Coordination and Initiation for Patients Who Inject Drugs.

With hepatitis C (HCV) incidence rising due to injection drug use, people who inject drugs (PWID) are a priority population for direct-acting antivirals (DAA). However, significant barriers exist. At our institution, hospitalized PWID were screened for HCV but not effectively linked to care. To improve retention in HCV care among hospitalized PWID. Quaternary academic center in the Southeast US from August 2021 through August 2022. Hospitalized PWID with HCV. E-consultation-prompted care coordination and HCV treatment with outpatient telehealth. Care cascades were constructed to assess retention and HCV treatment, with the primary outcome defined as DAA completion or sustained virologic response after week 4. Of 28 patients, 11 started DAAs inpatient, 8 initiated outpatient, and 9 were lost to follow-up or transferred care. Overall, 82% were linked to care and 52% completed treatment. For inpatient initiators, 73% achieved the outcome. Of non-inpatient initiators, 71% were linked to care, 53% started treatment, and 36% achieved the outcome. Inpatient HCV treatment coordination, including DAA initiation, and telehealth follow-up, was feasible and highly effective for hospitalized PWID. Future steps should address barriers to inpatient DAA treatment and expand this model to other similar patient populations.

Sustained virologic response from hepatitis C from an emergency department screening & linkage program: A retrospective review

IntroductionThe role of the Emergency Department (ED) as a vital constituent in Hepatitis C (HCV) screening has become increasingly evident. A key component of the ED's role in HCV screening is the ability to effectively link HCV-RNA positive patients to definitive, HCV-specific care, to include direct-acting antiviral (DAA) medication with resultant sustained virologic response (SVR). We sought to consider the rate of HCV-specific linkage, DAA initiation, and SVR obtained in HCV patients identified from an ED screening program. MethodsA retrospective chart review was conducted in February of 2022 of all individuals who participated in an opt-out ED-based HCV screening program between January 2018 and December 2019. Data was disaggregated by race, gender, age/birth cohort, insurance status, and achievement of sustained virologic response (SVR). Bivariate analysis using Pearson's chi-square was utilized to compare outcomes based on insurance status, race, sex, and birth cohort. ResultsOf 66,634 individuals screened for HCV during the study period, 885 (1.33%) patients were RNA-positive. Of those individuals, 121 (13.67%) were linked to HCV-specific care. Of those linked, the majority (66.9%) were male, white (66.1%; 33.1% Black), baby boomers or older (53.7%) and publicly insured (57.9%; private insurance 23.1%, self-pay 19%). Among linked patients, 88 (72.7%) started DAA medication. Mirroring linked demographics, majority were male (64.8%), white (64.8%), baby boomers or older (52.3%), and publicly insured (57.6%). White patients initiated on DAA were more likely to obtain SVR (64.9% versus 41.9% Black; p = .04) and uninsured patients were more likely to obtain SVR (82.4% versus 50.7% insured; p = .02). Bivariate consideration of SVR-patients specifically demonstrates that Black patients tended to be older, with significant overrepresentation of Baby boomers (77.5%) as compared to whites (37.5%; p < .0001). Black patients were also more likely to be publicly insured (82.5%) while white patients were more likely to have private insurance (28.8%) or be uninsured (26.3%) than their Black counterparts (12.5% and 5% respectively; p < .05). ConclusionAn ED-based HCV screening program can result in successful HCV-specific linkage and care, to include DAA initiation and ultimately, SVR. Among linked patients, specific cohort considerations may demonstrate differences in age and insurance status which may have implications on DAA application and adherence, and therefore, individual ability to achieve SVR.

Health Insurance and Initiation of Direct-Acting Antivirals for Hepatitis C in US Women With Human Immunodeficiency Virus.

Direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) is well tolerated, cost-effective, and yields high sustained virologic response rates, yet it has remained financially inaccessible to many patients. Participants of the Women's Interagency HIV Study (an observational US cohort) with human immunodeficiency virus (HIV) and HCV (RNA+) reporting no prior hepatitis C treatment were followed for DAA initiation (2015-2019). We estimated risk ratios (RRs) of the relationship between time-varying health insurance status and DAA initiation, adjusting for confounders with stabilized inverse probability weights. We also estimated weighted cumulative incidences of DAA initiation by health insurance status. A total of 139 women (74% Black) were included; at baseline, the median age was 55 years and 86% were insured. Most had annual household incomes ≤$18 000 (85%); advanced liver fibrosis (21%), alcohol use (45%), and recreational drug use (35%) were common. Across 439 subsequent semiannual visits, 88 women (63%) reported DAA initiation. Compared with no health insurance, health insurance increased the likelihood of reporting DAA initiation at a given visit (RR, 4.94; 95% confidence limit [CL], 1.92 to 12.8). At 2 years, the weighted cumulative incidence of DAA initiation was higher among the insured (51.2%; 95% CL, 43.3% to 60.6%) than the uninsured (3.5%; 95% CL, 0.8% to 14.6%). Accounting for clinical, behavioral, and sociodemographic factors over time, health insurance had a substantial positive effect on DAA initiation. Interventions to increase insurance coverage should be prioritized to increase HCV curative therapy uptake for persons with HIV.

Impact of direct-acting antiviral treatment for hepatitis C on cardiovascular diseases and extrahepatic cancers.

The impact of direct-acting antivirals (DAAs) on extrahepatic complications in chronic hepatitis C (CHC) patients remains poorly described. We estimated the association of DAAs with cardiovascular events and extrahepatic cancers. The prospective ANRS CO22 HEPATHER cohort was enriched with individual data until December 2018 from the French Health Insurance Database (SNDS). CHC patients were enrolled between August 2012 and December 2015 in 32 French hepatology centers. A total of 8148 CHC adults were selected. Cardiovascular events (stroke, acute coronary syndrome, pulmonary embolism, heart failure, arrhythmias and conduction disorders [ACD], peripheral arterial disease [PAD]) and extrahepatic solid cancers were derived from the SNDS. Associations between DAAs and extrahepatic events were estimated using marginal structural models, with adjustments for clinical confounders. Analyses of 12 905 person-years of no DAA exposure and 22 326 person-years following DAA exposure showed a decreased risk of PAD after DAA exposure (hazard ratio [HR], 0.54; 95% CI, 0.33-0.89), a beneficial effect of DAAs on overall cardiovascular outcomes in patients with advanced fibrosis (aHR, 0.58; 95% CI, 0.42-0.79), and an increased risk of ACD (hazard ratio [HR], 1.46; 95% CI, 1.04-2.04), predominant after the first year following DAA initiation. There was no association between DAAs and extrahepatic cancer risk (HR, 1.23; 95% CI, 0.50-3.03). DAAs were not associated with extrahepatic cancer development or reduction. They were associated with a decreased risk of PAD and an increased risk of ACD, supporting long-term cardiac monitoring after DAA therapy.

Adherence to opioid agonist therapy predicts uptake of direct-acting antivirals in people who use drugs: results from the French national healthcare database (the ANRS FANTASIO study)

BackgroundOpioid agonist therapy (OAT) is associated with reduced injection, reduced HCV transmission, and more opportunities to initiate hepatitis C virus (HCV) treatment in people who use drugs (PWUD). We aimed to study the extent to which adherence to OAT was predictive of increased uptake of direct-acting antivirals (DAA) in PWUD with chronic HCV infection.MethodsUsing the French national healthcare system database, we targeted PWUD (i.e. with a history of OAT) who had chronic HCV infection and were eligible for DAA during 2014–2016. Adherence to OAT was computed as a time-varying variable expressing the proportion of days covered by OAT receipt, over any six-month interval before DAA receipt. We used a Cox proportional hazards model to estimate the association between adherence to OAT and the rate of DAA uptake after adjustment for age, sex, alcohol use disorder, socioeconomic status, and liver disease severity.ResultsAmong the 22,615 persons included in the ANRS FANTASIO study, 3438 (15.2%) initiated DAA during the study period. After multivariable adjustment, adherence to OAT was associated with a higher rate of DAA initiation. However, this association was not linear, and only individuals on OAT for 20% or more of the time in the previous six-month period had a higher rate of DAA initiation (adjusted hazard ratio [95% confidence interval]: 1.28 [1.18–1.38]). Other variables associated with DAA initiation were male sex, older age, cirrhosis or liver cancer, and higher socioeconomic status.ConclusionsAdherence to OAT is a major predictor of DAA initiation in PWUD living with chronic HCV infection in France. Our results also suggest that even moderate adherence to OAT can facilitate DAA uptake. Adequate HCV training for OAT prescribers together with interventions to ensure adherence to OAT will help improve DAA initiation rates and reach HCV elimination goals.

Acute myeloid leukaemia following direct acting antiviral drugs in HCV-infected patients: A 10 years’ retrospective single-center study

BackgroundAfter several cases of peculiar hematological malignancies following introduction of new oral anti-hepatitis C virus (HCV) treatments in our recent practice, we aimed to systematically identify all cases of hematological malignancies (HM) in patients with chronic HCV infection and to compare them according to the prescription of oral anti-HCV Direct Acting Antivirals (DAA) treatment or not. Material/methodsIn this single-center retrospective observational study, we included all patients with confirmed HM and chronic HCV infection managed between 2010 and 2019 in the Pitié-Salpêtrière hospital, Paris. Non-inclusion criteria were a benign hematological disorder, an HM preceding chronic HCV infection and HCV acute infection. We compared characteristics of patients who received DAA before HM diagnosis to those with no DAA before HM. ResultsOver the 10 years, 61 cases of HM among HCV infected patients were identified (female 29%, median age of 58.0 years [IQR 17]). Twenty-one received DAA before the onset of HM (Group DAA+) and 40 did not (Group DAA-) including 22 having received DAA after HM. In the DAA+ group, oral NS5B, NS5A and NS3A inhibitors were used in 90, 76 and 29% respectively. HM developed in the two years following DAA initiation in 76%. Eight (38%) had Non-Hodgkin Lymphoma, 5 (24%) had an Acute Myeloid Leukaemia (AML) including two with a mixed phenotype, 2 each had Hodgkin Lymphoma, Multiple Myeloma or a myeloproliferative disorder and one each had a chronic Lymphocytic Leukaemia or AL Amyloidosis. In the Group DAA–, HM were NHL in 20(50%) patients, Myeloproliferative neoplasms in 7 (17%), Multiple Myeloma in 5, Hodgkin Lymphoma in 3, Myelodysplastic syndrome and AML in 2 (5%) each and Acute Lymphoblastic Leukaemia in one. No significant difference between the groups DAA + and – was found according to age, sex, HCV genotype, viral load, co-infection or type and exposition of previous HCV treatments. AML, liver transplantation and cirrhosis were significantly more frequent in the DAA+ group (p = 0.020, 0.045 and 0.032, respectively). ConclusionAML seemed more frequent after using DAA treatments, notably in severe HCV patients including cirrhotic and/or liver transplanted patients. A multicentric observational study is ongoing to confirm and explore the results.

Prediction of hepatocellular carcinoma in Hepatitis C patients with advanced fibrosis after sustained virologic response

Background & AimsPrediction of hepatocellular carcinoma (HCC) occurrence in patients with chronic hepatitis C (HCV) who achieved a sustained virological response (SVR) after direct acting antivirals (DAAs) remains challenging. MethodsAmong HCC-free HCV patients with advanced fibrosis enrolled in the ANRS CO22 HEPATHER cohort who achieved SVR 12 weeks after treatment with DAAs, HCC predictive models were developed using Cox multivariable regression. The derived score was externally validated in a large Egyptian cohort. Our main outcome was the HCC-free survival. ResultsDuring follow-up (median 3.05 years), 153 out of 3531 patients developed a HCC. Main variables associated with HCC occurrence were: male gender, HCV genotype 3, esophageal varices, albumin < 40 g/L, total bilirubin >11 µmol/L and hypercholesterolemia before DAA initiation, together with age > 58 years, FIB-4 index ≥3.25 evaluated at SVR. A score was established allowing the stratification of patients by high (score ≥ 12/22), intermediate (7 ≤ score <12) and low risk of HCC (score < 7/22) with 3-yrs HCC incidence of 18.96%, 5.50% and 1.65%, respectively. The integrated time‐dependent area under the ROC curve (i-AUC) was 0.76 in our patients and 0.61 in the validation cohort. ConclusionThe externally validated HEPATHER HCC score has good short-term predictive performance in HCV- patients who achieved SVR12 after DAAs allowing to identify high-risk patients in whom HCC screening may be cost-effective and low-risk patients in whom HCC screening may be superfluous in the first 3 years after SVR.

Real-world effectiveness of direct-acting antivirals in people living with human immunodeficiency virus and hepatitis C virus genotype 6 infections

BACKGROUNDHepatitis C virus (HCV) genotype 6 (HCV-6) infection is prevalent predominantly in Southeast Asia, and the data on the virologic response of HCV-6 to direct-acting antivirals (DAAs) are sparse in people living with human immunodeficiency virus (HIV) (PLWH).AIMTo assess the virologic response of HCV-6 to DAAs in PLWH.METHODSFrom September 2016 to July 2019, PLWH coinfected with HCV-6 initiating DAAs were included. Laboratory investigations were performed at baseline, the end of treatment, and 12 wk off-therapy.RESULTSOf the 349 PLWH included (mean age 48.9 years, 82.5% men), 80.5% comprised people who inject drugs, 18.1% men who have sex with men, and 1.4% heterosexuals. Coexistent hepatitis B virus infection was present in 12.3% of the included PLWH, liver cirrhosis 10.9%, hepatocellular carcinoma 0.9%, and previous HCV treatment experience 10.9%. The mean baseline plasma HCV RNA was 6.2 log10 IU/mL. Treatment with glecaprevir/pibrentasvir was initiated in 51.9%, sofosbuvir/ledipasvir 41.5%, sofosbuvir/velpatasvir 6.3%, and sofosbuvir/daclatasvir 0.3%. At DAA initiation, antiretroviral therapy containing tenofovir alafenamide was given in 26.4%, tenofovir disoproxil fumarate 34.4%, non-tenofovir alafenamide/tenofovir disoproxil fumarate 39.3%, non-nucleoside reverse-transcriptase inhibitors 30.4%, protease inhibitors 4.0%, and integrase strand transfer inhibitors 66.8%; 94.8% of the included patients had CD4 counts ≥ 200 cells/mm3 and 96.0% had plasma HIV RNA < 50 copies/mL. Overall, 96.8% achieved undetectable plasma HCV RNA (< 30 IU/mL) at end of treatment; and 92.3% achieved sustained virologic response 12 wk off-therapy in the intention-to-treat analysis (93.5% in patients receiving sofosbuvir-based DAAs and 91.2% in those receiving glecaprevir/pibrentasvir).CONCLUSIONSimilar to the observation made in HIV-negative patients, sustained virologic response 12 wk off-therapy with DAAs is high in PLWH coinfected with HCV-6.

Risk of HIV viral rebound in HIV infected patients on direct acting antivirals (DAAs) treatment for HCV.

BackgroundThe dynamic of HIV-viral load (VL) remains poorly investigated in HIV/HCV patients under direct acting antivirals (DAAs).MethodsWe retrospectively evaluated HIV-VL at baseline (BL) during and up to 24 weeks post-DAAs in a cohort of 305 HIV-1/HCV patients, on ART and with no HIV virological failure (VF) in the 6 months before treatment with DAAs; during the period of observation VF was defined as confirmed VL≥50 copies/mL; virological blips (VB, transient, not confirmed, VL ≥50 copies/mL). Stepwise Cox regression models were fitted to estimate adjusted hazard ratios (aHR) of VF.ResultsFifteen VF occurred in 13 patients over 187 person-years of follow-up (PYFU): incidence rate (IR) of 8.0 per 100-PYFU (95% CI = 4.0–12.1); 29 VBs were detected in 26 patients over 184 PYFU: IR = 15.8 per 100-PYFU (95% CI = 10.0–21.5). The most prominent factor associated with VF was the presence of BL HIV residual viremia (RV = HIV-RNA detectable but not precisely quantifiable) [aHR = 12.26 (95% CI = 3.74–40.17), P<0.0001]. Other factors were ≥1 VBs in the 6 months before DAAs [aHR = 6.95 (95% CI = 1.77–27.37) P = 0.006] number of ART regimens failed before DAAs initiation [aHR (per more regimen) = 1.22 (95% CI = 1.04–1.42), P = 0.012] and age [aHR (per year older) = 1.16 (95% CI = 1.04–1.29), P = 0.010].ConclusionsOur findings underline the importance for close monitoring HIV-VL in selected patients. Whether this phenomenon is triggered by the rapid clearance of HCV remains to be established.

Особенности фенотипа В-лимфоцитов у больных хроническим вирусным гепатитом С в зависимости от генотипа вируса (до и после лечения препаратами прямого противовирусного действия)

Objective. To analyze the phenotype of B-lymphocytes in patients with chronic infection with hepatitis C virus (HCV) before and after treatment with direct-acting antivirals (DAAs) depending on the virus genotype. Patients and methods. This open-label clinical and immunological study included 111 HCV patients with a mean age of 43.4 ± 8.6 years who received DAAs: Sofosbuvir (400 mg) and Velpatasvir (100 mg) once a day for 12 weeks. We assessed the phenotypic diversity of B-lymphocytes in peripheral blood of HCV patients during therapy and after its completion depending on the virus genotype. Results. Prior to DAA initiation, HCV patients demonstrated elevated count of CD19+CD5+CD27+ B cells and CD23+ B cells along with a decreased count of CD19+CD5–CD27+ B cells compared to controls. After therapy with DAAs, HCV patients continued to have increased proportion of CD19+CD5+CD27+ cells and reduced proportion of CD19+CD5–CD27+ cells. Conclusion. The pretreatment phenotypic diversity of peripheral B cells in HCV patents did not depend on the HCV genotype and was characterized by increased levels of B1 memory cells and activated B cells of the main subpopulations, along with a decreased level of B2 memory cells. The changes in the count of different B-cell subpopulations after DAA therapy depend on HCV genotype and might be associated with the rate of virus elimination. Key words: B-lymphocytes, immune system, direct-acting antivirals, chronic hepatitis C

Barriers and facilitators related to HCV treatment uptake among HIV coinfected populations in Canada: Patient and treatment provider perceptions.

Direct-acting antiviral (DAA) uptake is challenging across HIV-hepatitis C (HCV) coinfected populations. This study sought to identify barriers and facilitators related to DAA uptake in priority populations in Canada. This qualitative descriptive study included 11 people living with HIV with a history of HCV and 15 HCV care providers. Participants were part of either nominal groups (n = 4) or individual interviews (n = 6) in which they identified and ranked barriers and facilitators to DAA uptake. Consolidated lists of barriers and facilitators were identified thematically. Patient participants highly ranked the following barriers: competing priorities and needs (ie, social instability and mental health), delays in care, lack of adherence, and polypharmacy. Provider participant top barriers were the following: competing priorities and needs (ie, social chaos), delays in care (eg, systemic barriers, difficulties engaging patients, lack of trained HCV providers), and HCV-related stigma. Patient participants identified having a strong network of health care providers, family, and friends, possessing intrinsic motivation, and DAAs being a simple and tolerable oral treatment as important facilitators. Provider participant top-ranked facilitators were having resources to identify hard-to-reach populations (eg, patient navigation, outreach), holistic care and addiction management, provider HCV education, and a strong network of interprofessional collaboration. The barriers to DAA initiation addressed by patients and providers overlapped, with some nuances. Multidisciplinary care fostering a strong supportive network and intrinsically motivated patients along with HCV education emerged as key facilitators. This study provides insights for developing potential strategies to improve DAA uptake among HIV-HCV coinfected people in Canada.

Potential interventions to support HCV treatment uptake among HIV co-infected people in Canada: Perceptions of patients and health care providers.

Increasing direct-acting antiviral (DAA) treatment uptake is key to eliminating HCV infection as a public health threat in Canada. People living with human immunodeficiency virus (HIV) and hepatitis C (HCV) co-infection face barriers to HCV treatment initiation. We sought to identify interventions that could support HCV treatment initiation based on patient and HCV care provider perspectives. Eleven people living with HIV with a history of HCV infection and 12 HCV care providers were recruited for this qualitative descriptive study. Participants created ranked-ordered lists of potential interventions during nominal groups (n = 4) and individual interviews (n = 6). Following the nominal group technique, transcripts and intervention lists underwent thematic analysis and ranking scores were merged to create consolidated and prioritized lists from patient and provider perspectives. Patient participants identified a total of eight interventions. The highest-ranked interventions were multidisciplinary clinics, HCV awareness campaigns and patient education, nurse- or pharmacist-led care, peer involvement, and more and better-prepared health professionals. Provider participants identified 11 interventions. The highest-ranked were mobile outreach, DAA initiation at pharmacies, a simplified process of DAA prescription, integration of primary and specialist care, and patient-centred approaches. Participants proposed alternatives to hospital-based specialist HCV care, which require increasing capacity for nurses, pharmacists, primary care providers, and peers to have more direct roles in HCV treatment provision. They also identified the need for structural changes and educational initiatives. In addition to optimizing HCV care, these interventions might result in broader benefits for the health of HIV-HCV co-infected people.

Study of Quasispecies Complexity and Liver Damage Progression after Liver Transplantation in Hepatitis C Virus Infected Patients.

Cirrhosis derived from chronic hepatitis C virus (HCV) infection is still a common indication for liver transplantation (LT). Reinfection of the engrafted liver is universal in patients with detectable viral RNA at the time of transplant and causes fast progression of cirrhosis (within 5 years) in around one-third of these patients. To prevent damage to the liver graft, effective direct-acting antiviral (DAA) therapy is required as soon as possible. However, because of post-LT clinical instability, it is difficult to determine the optimal time to start DAAs with a low risk of complications. Evaluate changes in quasispecies complexity following LT and seek a predictive index of fast liver damage progression to determine the timing of DAA initiation. HCV genomes isolated from pre-LT and 15-day post-LT serum samples of ten patients, who underwent orthotopic LT, were quantified and sequenced using a next-generation sequencing platform. Sequence alignments, phylogenetic trees, quasispecies complexity measures, biostatistics analyses, adjusted R2 values, and analysis of variance (ANOVA) were carried out. Three different patterns of reinfection were observed (viral bottlenecking, conserved pre-LT population, and mixed populations), suggesting that bottlenecking or homogenization of the viral population is not a generalized effect after liver graft reinfection. None of the quasispecies complexity measures predicted the future degree of liver damage. Higher and more uniform viral load (VL) values were observed in all pre-LT samples, but values were more dispersed in post-LT samples. However, VL increased significantly from the pre-LT to 15-day post-LT samples in patients with advanced fibrosis at 1-year post-LT, suggesting that a VL increase on day 15 may be a predictor of fast liver fibrosis progression. HCV kinetics after LT differ between patients and are not fibrosis-dependent. Higher VL at day 15 post-LT versus pre-LT samples may predict fast liver fibrosis progression.