Real-world experience for the outcomes and costs of treating hepatitis C patients: Results from the German Hepatitis C-Registry (DHC-R).

BACKGROUND & AIMS: With long-term consequences like the development of liver cirrhosis and hepatocellular carcinoma, chronic hepatitis C virus (HCV) infection is associated with a significant health burden. Information on HCV treatment outcomes and costs in routine care is still rare, especially for subgroups. The aim of this study was to analyse the treatment outcomes and costs of subgroups in routine care and to compare them over time with previous analyses. METHODS: Data were derived from a noninterventional study including a subset of 10298 patients receiving DAAs with genotypes 1 and 3. Sociodemographic, clinical parameters and costs were collected using a web-based data recording system. The total sample was subdivided according to treatment regimen, cirrhosis status as well as present HIV infection and opioid substitution treatment (OST). RESULTS: 95% of all patients achieved SVR. Currently used DAA showed higher SVR-rates and less adverse events (AE) compared to former treatments. Concerning subgroups, cirrhotic patients, HIV-coinfected patients and OST patients showed lower but still high SVR-rates. In comparison, cirrhotic had considerably longer treatment duration and more frequent (serious) AE. Overall, average treatment costs were €48470 and costs per SVR were €51129; for currently used DAAs costs amounted to €30330 and costs per SVR to €31692. After the end of treatment, physical health is similar to the general population in all patients except cirrhotic. Mental health remains far behind in all subgroups, even for currently used DAA. CONCLUSIONS: Over time, some relevant factors developed positively (SVR-rates, costs, treatment duration, adverse events, health-related quality of life (HRQoL)). Further research on HRQoL, especially on mental health, is necessary to evaluate the differences between subgroups and HRQoL over time and to identify influencing factors.

Outcomes of men with HIV and germ cell cancer: Results from an international collaborative study.

BACKGROUND: Previous studies have shown that men with HIV and germ cell cancer (HIV-GCC) have inferior overall survival (OS) in comparison with their HIV-negative counterparts. However, little information is available on treatments and outcomes of HIV-GCC in the era of combination antiretroviral therapy (cART). METHODS: This study examined men living with HIV who were 18 years old or older and had a diagnosis of histologically proven germ cell cancer (GCC). The primary outcomes were OS and progression-free survival (PFS). RESULTS: Data for 89 men with a total of 92 HIV-GCCs (2 synchronous GCCs and 1 metachronous bilateral GCC) were analyzed; among them were 64 seminomas (70%) and 28 nonseminomas (30%). The median age was 36 years, the median CD4 T-cell count at GCC diagnosis was 420 cells/µL, and 77% of the patients on cART had an HIV RNA load < 500 copies/mL. Stage I disease was found in 44 of 79 gonadal GCCs (56%). Among 45 cases with primary disseminated GCC, 78%, 18%, and 4% were assigned to the good-, intermediate-, and poor-prognosis groups, respectively, of the International Germ Cell Cancer Collaborative Group. Relapses occurred in 14 patients. Overall, 12 of 89 patients (13%) died. The causes of death were refractory GCC (n = 5), an AIDS-defining illness (n = 3), and other causes (n = 4). After a median follow-up of 6.5 years, the 5- and 10-year PFS rates were 81% and 73%, respectively, and the 5- and 10-year OS rates were 91% and 85%, respectively. CONCLUSIONS: The 5- and 10-year PFS and OS rates of men with HIV-GCC were similar to those reported for men with HIV-negative GCC. Patients with HIV-GCC should be managed identically to HIV-negative patients. LAY SUMMARY: Men living with HIV are at increased risk for germ cell cancer (GCC). Previous studies have shown that the survival of men with HIV-associated germ cell cancer (HIV-GCC) is poorer than the survival of their HIV-negative counterparts. This study examined the characteristics, treatments, and outcomes of 89 men with HIV-GCC in the era of effective combination antiretroviral therapies. The long-term outcomes of men with HIV-GCC were similar to those reported for men with HIV-negative GCC. Patients with HIV-GCC should be managed identically to HIV-negative patients.

HIV pre-exposure prophylaxis was associated with no impact on sexually transmitted infection prevalence in a high-prevalence population of predominantly men who have sex with men, Germany, 2018 to 2019.

IntroductionDespite increased use of pre-exposure prophylaxis (PrEP) in Germany, HIV infection rates are not declining and little is known about how this prevention method affects the prevalence of sexually transmitted infections (STI) among men who have sex with men (MSM).AimWe studied, in a large multicentre cohort, STI point prevalence, co-infection rates, anatomical location and influence of PrEP.MethodsThe BRAHMS study was a prospective cohort study conducted at 10 sites in seven major German cities that enrolled MSM reporting increased sexual risk behaviour. At screening visits, MSM were tested for Mycoplasma genitalium (MG), Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT) and Treponema pallidum (TP), and given a behavioural questionnaire. With binomial regression, we estimated prevalence ratios (PR) and 95% confidence intervals (CI) for the association of PrEP and STI.ResultsWe screened 1,043 MSM in 2018 and 2019, with 53.0% currently using PrEP. At screening, 370 participants (35.5%) had an STI. The most common pathogen was MG in 198 (19.0%) participants, followed by CT (n = 133; 12.8%), NG (n = 105; 10.1%) and TP (n = 37; 3.5%). Among the 370 participants with at least one STI, 14.6% (n = 54) reported STI-related symptoms. Infection prevalence was highest at anorectal site (13.4% MG, 6.5% NG, 10.2% CT). PrEP use was not statistically significant in adjusted models for STI (PR: 1.10; 95% CI: 0.91-1.32), NG/CT, only NG or only CT.ConclusionsPrevalence of asymptomatic STI was high, and PrEP use did not influence STI prevalence in MSM eligible for PrEP according to national guidelines.

[HIV First Diagnoses in Germany in 2014 - A Regional Analysis]. / HIV-Erstdiagnosen in Deutschland im Jahr 2014 ­ eine regionale Analyse.

BACKGROUND: Information on testing units in health care is scarce, particularly the group of late-presenters among the HIV-first diagnoses is still a challenge in Germany. AIM: Analysis of the impact of testing units on and reasons for the prevalence of HIV-first diagnoses and late presentation, taking 2014 for illustrative purposes. MATERIAL AND METHODS: Cross-sectional analysis of all individuals, treated in the Network HIV-Regional who were first diagnosed with HIV in 2014; patient characteristics, demographic and clinical data, including information on HIV testing were collected retrospectively and in a decentralised manner, pseudonymized and statistically evaluated. RESULTS: A total of 971 individuals with HIV-first diagnosis from 31 specialised care centres throughout Germany (15 hospitals, 16 private practices) represented 27.5% of all National HIV-first diagnoses -registrations from Robert Koch Institute for 2014, with similar results for CD4-cell count and HIV-transmission risk. The most common test site was a hospital (34.8%), followed by the office of a family doctor (19.6%) and medical specialist (16.1%). If the first diagnosis was established in hospital, then the patients were on average older than those tested on an ambulant care basis (42 vs. 37 years, p=0.001); moreover, the HI-viral load was higher (585 vs. 270 thousand copies/mL, p<0.001) and the CD4-cell count lower (265 vs. 414/µL, p<0.001). In 208/971 individuals with first diagnosis, at least one AIDS-defining disease was found, most frequently pneumocystis-pneumonia (43.8%), candidiasis (36.5%) and Kaposi sarcoma (10.6%). A regional comparison revealed that in eastern Germany, for first diagnosed HIV-patients were younger, had a higher HIV-RNA viral load and also more often clinical AIDS. CONCLUSION: This analysis of HIV-Regional for 2014 enables a deeper insight into HIV first diagnoses, on the eve of the introduction of important prevention tools in Germany, e. g., HIV home testing and pre-exposure prophylaxis. This cross-sectional analysis was representative for Germany and underscores the importance of specialised hospitals, in particular for eastern Germany, and furthermore the involvement of late-presenters into HIV health care.

The changing characteristics of patients infected with chronic hepatitis C virus from 2014 to 2019: Real-world data from the German Hepatitis C-Registry (DHC-R).

The number of patients diagnosed with hepatitis C virus (HCV) is markedly higher than the number initiating treatment indicating gaps in the care cascade, likely centred around reaching at-risk populations. Understanding changing characteristics of patients with HCV allows for targeted programs that increase linkage to care. We investigated changes in demographic and clinical characteristics of patients registered in the German Hepatitis C-Registry (DHC-R) from 1 January 2014 to 31 December 2019. The DHC-R is an ongoing, noninterventional, multicentre, prospective, observational cohort registry including 327 German centres. Patient characteristics were analysed over time in 7 phases for all patients completing a screening visit. Overall, 14,357 patients were enrolled. The percentage of treatment-naïve/non-cirrhotic patients increased from 34.4% in phase 1 (1 January-31 December 2014) to 68.2% in phase 7 (1 August-31 December 2019). The proportion of migrants, alcohol users, people who inject drugs, and those receiving opiate substitution therapy increased in later registry phases. Most patients (60.1%) were receiving comedication at baseline. The most prescribed comedications were drugs used to treat opioid dependence which increased from 9.2% in phase 1 to 24.0% in phase 7. The patients' mean age decreased from 52.3 years in phase 1 to 48.7 years in phase 7. From 2014 to 2019, the proportion of at-risk patients enrolling in the registry increased. To eliminate viral hepatitis as a major public health threat, a continued commitment to engaging underserved populations into the HCV care cascade is needed.

Glecaprevir/pibrentasvir is safe and effective in hepatitis C patients with cirrhosis: Real-world data from the German Hepatitis C-Registry.

Glecaprevir/pibrentasvir is a pangenotypic direct-acting antiviral regimen approved for treating chronic hepatitis C virus. Real-world use of protease-inhibitor-containing regimens requires further evaluation in patients with cirrhosis. We evaluated the real-world safety and effectiveness of glecaprevir/pibrentasvir in patients with cirrhosis from the German Hepatitis C-Registry who initiated treatment between 2 August 2017 and 30 June 2019. Overall, 131 patients received 12-week (on-label) treatment and 51 received 8-week (off-label) treatment. No patient discontinued treatment due to adverse events. Four patients had serious adverse events; none were considered related to glecaprevir/pibrentasvir. Two patients had total bilirubin > 5 × upper limit of normal (ULN) during treatment. Three patients had alanine aminotransferase and three patients had aspartate aminotransferase > 3 × ULN. Rates of sustained virologic response were 100% (86/86) for 86 patients with available data. Glecaprevir/pibrentasvir treatment was well-tolerated and highly effective in patients with chronic hepatitis C and cirrhosis in real-world practice.

Physical and mental health in HIV-infected patients with virological success and long-term exposure to antiretroviral therapy.

In people living with HIV (PLWH), a decade-long antiretroviral therapy (ART) poses new challenges regarding physical and mental health. The aim of this cross-sectional study is to investigate the health-related quality of life (HRQOL) in adult HIV-infected patients with viral suppression and an ART exposure for at least 5 years in three German HIV centers. Patients were evaluated by the ACTG Augmented Symptoms Distress Module (ASDM) and the SF-12 Health Survey. Among 894 patients, symptom-related distress was highly prevalent. The most common symptoms were fatigue, insomnia, sadness and depression, sexual dysfunction, and changes in body appearance. In the multivariate analysis, ART duration, age and depression were significantly associated with a higher overall symptom summary score. Self-reported mean SF-12 scores were lower for mental health and younger patients compared to the standard random sample of a healthy German population. Depression and occupational status were significantly related to a lower physical component summary score, by contrast older age was associated with higher scores in the mental component summary, implying more favorable mental health status. In this large group of PLWH, the degree of symptom-related distress was high. Mental and physical health should be considered an integral part of ongoing HIV care.

Factors associated with testing for HIV and hepatitis C among behaviorally vulnerable men in Germany: a cross-sectional analysis upon enrollment into an observational cohort.

BACKGROUND: HIV and hepatitis C virus (HCV) have shared routes of transmission among men who have sex with men (MSM). Routine testing facilitates early diagnosis and treatment, thereby preventing morbidity and onward transmission. We evaluated factors associated with HIV and HCV testing in a behaviorally vulnerable cohort of predominantly MSM. METHODS: From June 2018 through June 2019, the BRAHMS study enrolled adults at ten German outpatient clinics that serve gender and sexual minority populations. Participants completed behavioral questionnaires that captured prior experience with HIV and HCV testing. Multivariable robust Poisson regression was used to evaluate factors potentially associated with testing in the previous 6 months. RESULTS: Among 1017 participants with median age 33 (interquartile range 28-39) years, 1001 (98.4%) reported any lifetime history of HIV testing and 787 (77.4%) reported any HCV testing, including 16 (1.6%) known to be living with HCV. Testing within the last 6 months was reported by 921 (90.6%) and 513 (50.4%) for HIV and HCV, respectively. Recent HIV testing was more common among participants with higher education level and recent HCV testing. Recent HCV testing was more common among participants with non-cisgender identity, lifetime history of illicit drug use, hepatitis B immunity or infection, and recent HIV testing. CONCLUSION: Prior testing for HIV was common in this cohort, but interventions are needed to improve HCV risk stratification and access to testing. HIV testing infrastructure can be successfully leveraged to support HCV testing, but differentiated preventive care delivery is needed for some vulnerable populations.

High effectiveness of recommended first-line antiretroviral therapies in Germany: a nationwide, prospective cohort study.

PURPOSE: Current German/Austrian antiretroviral treatment guidelines recommend more than 20 combination regimens for first-line therapy, without a preference. Regimens include two nucleoside reverse transcriptase inhibitors (NRTIs) plus either an integrase strand transfer inhibitor (INSTI), a non-NRTI (NNRTI) or a boosted protease inhibitor (PI). The objective was to examine the outcomes of recommended first-line ART in Germany. METHODS: This nationwide observational study included treatment-naïve chronically HIV-1 infected patients receiving one of the recommended first-line regimens. Patients were allocated to three arms (INSTI, NNRTI, PI) and were prospectively followed for 24 months. Delayed treatment initiation was defined by a baseline CD4 T-cell count of < 350/µl or CDC clinical stage C. RESULTS: Among a total of 434 patients enrolled, virologic failure was rare and occurred in 4.3% (6/141) in the PI arm, in 3.3% (4/122) in the NNRTI arm and in 0.6% (1/171) in the INSTI arm (p = 0.10). De novo drug resistance mutations developed in only two patients in the NNRTI arm. Nonetheless, treatment modifications were frequent (51%) and mostly performed for strategic reasons. Retention on all initial compounds at month 24 was 64%, 49%, and 22% in the INSTI, NNRTI and PI arms respectively. Delayed treatment initiation was common (47%) and more frequently observed in patients in the PI arm. It was not associated with virological failure. CONCLUSION: High efficacy and low virological failure rates were observed with recommended first-line regimens independent of delayed treatment initiation, chosen regimen and subsequent treatment modifications, demonstrating the validity of the current treatment guidelines.

Sofosbuvir, velpatasvir, and voxilaprevir for patients with failure of previous direct-acting antiviral therapy for chronic hepatitis C: Results from the German Hepatitis C-Registry (DHC-R).

Despite the high effectiveness of direct-acting antivirals for the treatment of hepatitis C, a small proportion of patients do not respond to approved regimens. The combination regimen of SOF/VEL/VOX was recently approved for patients with failure to prior NS5A-based treatment. In this German real-world cohort including patients with cirrhosis (27.3 %) and previous decompensation events, 12 weeks of SOF/VEL/VOX resulted in high virologic response rates irrespective of disease severity and prior DAA regimen. Adverse events were mostly mild or moderate and comparable to those seen in the approval studies.

Incidence and risk factors for relapses in HIV-associated non-Hodgkin lymphoma as observed in the German HIV-related lymphoma cohort study.

Outcome of HIV-infected patients with AIDS-related lymphomas has improved during recent years. However, data on incidence, risk factors, and outcome of relapses in AIDS-related lymphomas after achieving complete remission are still limited. This prospective observational multicenter study includes HIV-infected patients with biopsy- or cytology-proven malignant lymphomas since 2005. Data on HIV infection and lymphoma characteristics, treatment and outcome were recorded. For this analysis, AIDS-related lymphomas patients in complete remission were analyzed in terms of their relapse- free survival and potential risk factors for relapses. In total, 254 of 399 (63.7%) patients with AIDS-related lymphomas reached a complete remission with their first-line chemotherapy. After a median follow up of 4.6 years, 5-year overall survival of the 254 patients was 87.8% (Standard Error 3.1%). Twenty-nine patients relapsed (11.4%). Several factors were independently associated with a higher relapse rate, including an unclassifiable histology, a stage III or IV according to the Ann Arbor Staging System, no concomitant combined antiretroviral therapy during chemotherapy and R-CHOP-based compared to more intensive chemotherapy regimens in Burkitt lymphomas. In conclusion, complete remission and relapse rates observed in our study are similar to those reported in HIV-negative non-Hodgkin lymphomas. These data provide further evidence for the use of concomitant combined antiretroviral therapy during chemotherapy and a benefit from more intensive chemotherapy regimens in Burkitt lymphomas. Modifications to the chemotherapy regimen appear to have only a limited impact on relapse rate.

Combination of vaniprevir with peginterferon and ribavirin significantly increases the rate of SVR in treatment-experienced patients with chronic HCV genotype 1 infection and cirrhosis.

BACKGROUND & AIMS: The combination of vaniprevir (a NS3/4A protease inhibitor) with peginterferon and ribavirin was shown to increase rates of sustained virologic response (SVR) significantly, compared with peginterferon and ribavirin alone, in treatment-experienced patients with chronic hepatitis C virus (HCV) genotype 1 infection without cirrhosis. We performed a blinded, randomized, controlled trial of the effects of vaniprevir with peginterferon and ribavirin in patients with cirrhosis who did not respond to prior therapy with peginterferon and ribavirin. METHODS: Treatment-experienced patients (88% white and 35% prior null responders) with HCV genotype 1 infection and compensated cirrhosis were assigned randomly to groups given vaniprevir (600 mg twice daily) with peginterferon and ribavirin for 24 weeks (n = 16), vaniprevir (600 mg twice daily) for 24 weeks with peginterferon and ribavirin for 48 weeks (n = 14), vaniprevir (300 mg twice daily) with peginterferon and ribavirin for 48 weeks (n = 15), vaniprevir (600 mg twice daily) with peginterferon and ribavirin for 48 weeks (n = 15), or placebo with peginterferon and ribavirin for 48 weeks (n = 14, control). Cirrhosis was documented by liver biopsy (84%) or noninvasive methods (16%). Before randomization, participants were stratified based on their historical response to peginterferon and ribavirin. RESULTS: In the primary analysis, SVR rates among patients in the respective vaniprevir groups were 9 of 15 (60.0%), 9 of 13 (69.2%), 8 of 15 (53.3%), and 10 of 13 (76.9%), compared with 2 of 14 (14.3%) in the control group (pairwise P values ≤ .016). Cirrhotic patients with null or partial responses to prior therapy achieved SVR less often than patients with prior breakthrough or relapse, although 42.1% of prior null responders in the vaniprevir groups achieved SVRs. Patients in the vaniprevir groups more frequently experienced mild-moderate nausea, vomiting, and diarrhea than controls; 5% developed grade 2 anemia compared with none in the control group (no patient developed grade 3 or 4 anemia). Among patients in the vaniprevir groups who experienced virologic failure, resistance-associated variants were detected predominantly at positions 155, 156, and 168 in the HCV protease gene. CONCLUSIONS: In a controlled phase 2B trial, vaniprevir with peginterferon and ribavirin significantly increased rates of SVR among treatment-experienced patients with chronic HCV genotype 1 infection, compared with re-treatment with peginterferon and ribavirin alone. Vaniprevir generally was well tolerated for up to 48 weeks in patients with compensated cirrhosis. ClinicalTrials.gov number, NCT00704405.

A phase 2B study of MK-7009 (vaniprevir) in patients with genotype 1 HCV infection who have failed previous pegylated interferon and ribavirin treatment.

BACKGROUND & AIMS: MK-7009 (vaniprevir) is a non-covalent competitive inhibitor of the hepatitis C virus (HCV) NS3/4A protease. This report presents the primary analysis results (safety and sustained viral response) of a phase 2b study of MK-7009 given in combination with peginterferon (PegIFN) alfa2a 180 µg weekly and ribavirin (RBV) 1000-1200 mg/day, for 24-48 weeks to non-cirrhotic patients who have failed previous PegIFN and RBV treatment. METHODS: We present results of a randomized, placebo-controlled, double-blind study of MK-7009 administered for 24-48 weeks in combination with PegIFN and RBV in 4 regimens to at least 40 patients per arm. Stratification by prior response to PegIFN and RBV was as follows: null response, partial response, breakthrough and relapse. HCV RNA was determined by Roche Cobas Taqman with a lower limit of detection (LLoD) of 10 IU/ml and a lower limit of quantification (LLoQ) of 25 IU/ml. RESULTS: SVR24 in patients on MK-7009+PegIFN and ribavirin (P/R) was statistically superior to placebo+P/R in all treatment groups (p<0.001). MK-7009 at 300 mg b.i.d. and 600 mg b.i.d. is generally well tolerated for use for up to 48 weeks of therapy. Patients in MK-7009 regimens had higher rates of gastrointestinal adverse events as compared to control (mostly mild to moderate). There were no significant differences in rates of anemia and rash between the MK-7009 regimens and control. CONCLUSIONS: In conclusion, patients treated with MK-7009 plus P/R experienced significant improvement in SVR compared to P/R control in a population of GT 1 experienced patients.

Vaniprevir with pegylated interferon alpha-2a and ribavirin in treatment-naïve patients with chronic hepatitis C: a randomized phase II study.

UNLABELLED: Vaniprevir (MK-7009) is a macrocyclic hepatitis C virus (HCV) nonstructural protein 3/4A protease inhibitor. The aim of the present phase II study was to examine virologic response rates with vaniprevir in combination with pegylated interferon alpha-2a (Peg-IFN-α-2a) plus ribavirin (RBV). In this double-blind, placebo-controlled, dose-ranging study, treatment-naïve patients with HCV genotype 1 infection (n = 94) were randomized to receive open-label Peg-IFN-α-2a (180 µg/week) and RBV (1,000-1,200 mg/day) in combination with blinded placebo or vaniprevir (300 mg twice-daily [BID], 600 mg BID, 600 mg once-daily [QD], or 800 mg QD) for 28 days, then open-label Peg-IFN-α-2a and RBV for an additional 44 weeks. The primary efficacy endpoint was rapid viral response (RVR), defined as undetectable plasma HCV RNA at week 4. Across all doses, vaniprevir was associated with a rapid two-phase decline in viral load, with HCV RNA levels approximately 3 log(10) IU/mL lower in vaniprevir-treated patients, compared to placebo recipients. Rates of RVR were significantly higher in each of the vaniprevir dose groups, compared to the control regimen (68.8%-83.3% versus 5.6%; P < 0.001 for all comparisons). There were numerically higher, but not statistically significant, early and sustained virologic response rates with vaniprevir, as compared to placebo. Resistance profile was predictable, with variants at R155 and D168 detected in a small number of patients. No relationship between interleukin-28B genotype and treatment outcomes was demonstrated in this study. The incidence of adverse events was generally comparable between vaniprevir and placebo recipients; however, vomiting appeared to be more common at higher vaniprevir doses. CONCLUSION: Vaniprevir is a potent HCV protease inhibitor with a predictable resistance profile and favorable safety profile that is suitable for QD or BID administration.

Prognostic impact of steatosis in the clinical course of chronic HCV infection-Results from the German Hepatitis C-Registry.

BACKGROUND: Liver steatosis is often observed in chronic HCV infection and associated to genotype or comorbidities. NAFLD is an important risk factor for end-stage liver disease. We aimed to analyse the course of NAFLD as a concomitant disease in a cohort of HCV patients. METHODS: The German Hepatitis C-Registry is a national multicenter real-world cohort. In the current analysis, 8789 HCV patients were included and separated based on the presence of steatosis on ultrasound and/or histology. Fibrosis progression was assessed by transient elastography (TE), ultrasound or non-invasive surrogate scores. RESULTS: At the time of study inclusion 12.3% (n = 962) of HCV patients presented with steatosis (+S) (higher rate in GT-3). Diabetes mellitus was more frequent in GT-1 patients. HCV patients without steatosis (-S) had a slightly higher rate of fibrosis progression (FP) over time (30.3%) in contrast to HCV patients +S (26%). This effect was mainly observed in GT-3 patients (34.4% vs. 20.6%). A larger decrease of ALT, AST and GGT from baseline to FU-1 (4-24 weeks after EOT) was found in HCV patients (without FP) +S compared to -S. HCV patients -S and with FP presented more often metabolic comorbidities with a significantly higher BMI (+0.58kg/m2) compared to patients -S without FP. This was particularly pronounced in patients with abnormal ALT. CONCLUSION: Clinically diagnosed steatosis in HCV patients does not seem to contribute to significant FP in this unique cohort. The low prevalence of steatosis could reflect a lower awareness of fatty liver in HCV patients, as patients -S and with FP presented more metabolic risk factors.

Real-World Safety, Effectiveness, and Patient-Reported Outcomes in Patients with Chronic Hepatitis C Virus Infection Treated with Glecaprevir/Pibrentasvir: Updated Data from the German Hepatitis C-Registry (DHC-R).

Using data from the German Hepatitis C-Registry (Deutsche Hepatitis C-Register, DHC-R), we report the real-world safety and effectiveness of glecaprevir/pibrentasvir (GLE/PIB) treatment and its impact on patient-reported outcomes (PROs) in underserved populations who are not typically included in clinical trials, yet who will be crucial for achieving hepatitis C virus (HCV) elimination. The DHC-R is an ongoing, non-interventional, multicenter, prospective, observational cohort study on patients treated for chronic HCV infection in Germany. The data cutoff was 17 January 2021. The primary effectiveness endpoint was sustained virologic response at post-treatment Week 12 (SVR12). Safety outcomes were assessed in all patients receiving GLE/PIB. PROs were assessed using the SF-36 survey. Of 2354 patients, 1964 had valid SVR12 data (intention-to-treat analysis). Of these, 1905 (97.0%) achieved SVR12 with rates similar across the comorbidities analyzed, except for people who actively use drugs (PWUD (active)) (86.4%). Excluding those who discontinued treatment and did not achieve SVR12, or were reinfected with HCV, the rate was 99.3%, with similar results regardless of comorbidity. PWUD (active) and those with psychiatric disorders had the most meaningful improvements in PROs. Adverse events (AEs) occurred in 631/2354 patients (26.8%), and serious AEs in 44 patients (1.9%). GLE/PIB was highly effective and well tolerated in this real-world study of patient groups key to HCV elimination.

Hepatitis C therapy with grazoprevir/elbasvir and glecaprevir/pibrentasvir in patients with advanced chronic kidney disease: data from the German Hepatitis C-Registry (DHC-R).

OBJECTIVES: Grazoprevir/elbasvir and glecaprevir/pibrentasvir (G/P) are the two preferred treatment options for patients with chronic hepatitis C virus (HCV) infection and a glomerular filtration rate (GFR) <30 mL/min. Both therapies have been separately analyzed in different real-life cohorts; however, a direct comparison has not been performed so far. We, therefore, analyzed safety and effectiveness of both regimens in a concerted real-life population. METHODS: The Germany Hepatitis C-Registry is a prospective national real-world registry. The analysis is based on 2773 patients with documented GFR at baseline treated with grazoprevir/elbasvir (N = 1041), grazoprevir/elbasvir + ribavirin (N = 53) and glecaprevir/pibrentasvir (N = 1679). RESULTS: A total of 93 patients with GFR <30 mL/min were treated with grazoprevir/elbasvir (N = 56), grazoprevir/elbasvir + ribavirin (N = 4), and glecaprevir/pibrentasvir (N = 33). They suffered significantly more frequent from diabetes mellitus, hypertension, and coronary heart disease than individuals with GFR >30 mL/min and showed the following baseline characteristics: 20.4, 55.9, 3.2, 12.9, and 5.3% were infected with HCV-genotypes 1a, 1b, 2, 3, and 4; 12.9% suffered from liver cirrhosis; 80.1% were treatment-naïve. Baseline characteristics except distribution of HCV-genotype 1b (n = 43/52 treated with grazoprevir/elbasvir) and sustained virologic response rates (SVR12) did not differ significantly between glecaprevir/pibrentasvir (SVR12: 100%) and grazoprevir/elbasvir (SVR12: 97.9%).Fatigue, headache, abdominal discomfort, and arthralgia were the most frequently reported adverse events without a statistical difference between grazoprevir/elbasvir and glecaprevir/pibrentasvir. CONCLUSION: In patients with chronic hepatitis C and a baseline GFR ≤30 mL/min grazoprevir/elbasvir and glecaprevir/pibrentasvir show an equally favorable safety profile and antiviral efficacy and can both be recommended for real-life use.

Cytochrome P450 2B6 (CYP2B6) and constitutive androstane receptor (CAR) polymorphisms are associated with early discontinuation of efavirenz-containing regimens.

OBJECTIVES: Cytochrome P450 2B6 (CYP2B6) is responsible for the metabolic clearance of efavirenz and single nucleotide polymorphisms (SNPs) in the CYP2B6 gene are associated with efavirenz pharmacokinetics. Since the constitutive androstane receptor (CAR) and the pregnane X receptor (PXR) correlate with CYP2B6 in liver, and a CAR polymorphism (rs2307424) and smoking correlate with efavirenz plasma concentrations, we investigated their association with early (<3 months) discontinuation of efavirenz therapy. METHODS: Three hundred and seventy-three patients initiating therapy with an efavirenz-based regimen were included (278 white patients and 95 black patients; 293 male). DNA was extracted from whole blood and genotyping for CYP2B6 (516G → T, rs3745274), CAR (540C → T, rs2307424) and PXR (44477T → C, rs1523130; 63396C → T, rs2472677; and 69789A → G, rs763645) was conducted. Binary logistic regression using the backwards method was employed to assess the influence of SNPs and demographics on early discontinuation. RESULTS: Of the 373 patients, 131 withdrew from therapy within the first 3 months. Black ethnicity [odds ratio (OR) = 0.27; P = 0.0001], CYP2B6 516TT (OR = 2.81; P = 0.006), CAR rs2307424 CC (OR = 1.92; P = 0.007) and smoking status (OR = 0.45; P = 0.002) were associated with discontinuation within 3 months. CONCLUSIONS: These data indicate that genetic variability in CYP2B6 and CAR contributes to early treatment discontinuation for efavirenz-based antiretroviral regimens. Further studies are now required to define the clinical utility of these associations.

Utilization and effectiveness of elbasvir/grazoprevir and adoption of resistance-associated substitutions testing in real-world treatment of hepatitis C virus genotype 1A infection: results from the German Hepatitis C-Registry.

BACKGROUND: For treatment of genotype 1a (GT1a) infection with elbasvir/grazoprevir, the German guidelines recommend a differentiated approach depending on baseline viral load (BVL). For low BVL ≤800 000 IU/mL, treatment with 12 weeks elbasvir/grazoprevir should be considered, whereas for high BVL >800 000 IU/mL, this regimen is only recommended in nonstructural protein 5A (NS5A) resistance-associated substitutions (RAS) absence. With present NS5A RAS or when RAS-testing is not available, 16 weeks elbasvir/grazoprevir + ribavirin is preferred. Here, we investigated the adherence to these recommendations and the effectiveness of elbasvir/grazoprevir in a large German Hepatitis C-Registry GT1a cohort. METHODS: From September 2016 until July 2018, 195 GT1a-infected patients were treated with elbasvir/grazoprevir ± ribavirin for 12-16 weeks. The primary outcome was per protocol SVR12 or SVR24. RESULTS: Mean age was 50 years, 89% were male, 19% had cirrhosis, 72% were treatment-naïve. Forty-five percent had low BVL ≤800 000 IU/mL, 55% high BVL >800 000 IU/mL, of whom 49 vs. 42% were baseline RAS-tested. Four patients with high (7.7%) and two with low BVL (5%) had NS5A RAS of whom 50% received elbasvir/grazoprevir+ribavirin, respectively. Ninety-four percent of patients with low and 65% with high BVL received elbasvir/grazoprevir without ribavirin. Thirty-five percent of patients with high BVL received ribavirin, mostly without prior RAS-testing. Per protocol sustained virologic response (SVR) by low vs. high BVL was 98.8 and 95.1%. All patients with NS5A RAS achieved SVR. CONCLUSIONS: In German, real-world most patients received elbasvir/grazoprevir without ribavirin. Ribavirin was mainly added in GT1a patients >800 000 IU/mL, who were not NS5A RAS tested. SVR rates were consistently high and comparable to clinical trial results.