Determining the lower limit of detection required for HCV viral load assay for test of cure following direct-acting antiviral-based treatment regimens: Evidence from a global data set.

Achieving global elimination of hepatitis C virus requires a substantial scale-up of testing. Point-of-care HCV viral load assays are available as an alternative to laboratory-based assays to promote access in hard to reach or marginalized populations. The diagnostic performance and lower limit of detection are important attributes of these new assays for both diagnosis and test of cure. Therefore, our objective was to determine an acceptable LLoD for detectable HCV viraemia as a test for cure, 12 weeks post-treatment (SVR12). We assembled a global data set of patients with detectable viraemia at SVR12 from observational databases from 9 countries (Egypt, the United States, United Kingdom, Georgia, Ukraine, Myanmar, Cambodia, Pakistan, Mozambique) and two pharmaceutical-sponsored clinical trial registries. We examined the distribution of HCV viral load at SVR12 and presented the 90th, 95th, 97th and 99th percentiles. We used logistic regression to assess characteristics associated with low-level virological treatment failure (defined as <1000 IU/mL). There were 5973 cases of detectable viraemia at SVR12 from the combined data set. Median detectable HCV RNA at SVR12 was 287,986 IU/mL. The level of detection for the 95th percentile was 227 IU/mL (95% CI 170-276). Females and those with minimal fibrosis were more likely to experience low-level viraemia at SVR12 compared to men (adjusted odds ratio AOR = 1.60 95% confidence interval [CI] 1.30-1.97 and those with cirrhosis (AOR = 1.49 95% CI 1.15-1.93). In conclusion, an assay with a level of detection of 1000 IU/mL or greater may miss a proportion of those with low-level treatment failure.

Changes in the associations of race and rurality with SARS-CoV-2 infection, mortality, and case fatality in the United States from February 2020 to March 2021: A population-based cohort study.

BACKGROUND: We examined whether key sociodemographic and clinical risk factors for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and mortality changed over time in a population-based cohort study. METHODS AND FINDINGS: In a cohort of 9,127,673 persons enrolled in the United States Veterans Affairs (VA) healthcare system, we evaluated the independent associations of sociodemographic and clinical characteristics with SARS-CoV-2 infection (n = 216,046), SARS-CoV-2-related mortality (n = 10,230), and case fatality at monthly intervals between February 1, 2020 and March 31, 2021. VA enrollees had a mean age of 61 years (SD 17.7) and were predominantly male (90.9%) and White (64.5%), with 14.6% of Black race and 6.3% of Hispanic ethnicity. Black (versus White) race was strongly associated with SARS-CoV-2 infection (adjusted odds ratio [AOR] 5.10, [95% CI 4.65 to 5.59], p-value <0.001), mortality (AOR 3.85 [95% CI 3.30 to 4.50], p-value < 0.001), and case fatality (AOR 2.56, 95% CI 2.23 to 2.93, p-value < 0.001) in February to March 2020, but these associations were attenuated and not statistically significant by November 2020 for infection (AOR 1.03 [95% CI 1.00 to 1.07] p-value = 0.05) and mortality (AOR 1.08 [95% CI 0.96 to 1.20], p-value = 0.21) and were reversed for case fatality (AOR 0.86, 95% CI 0.78 to 0.95, p-value = 0.005). American Indian/Alaska Native (AI/AN versus White) race was associated with higher risk of SARS-CoV-2 infection in April and May 2020; this association declined over time and reversed by March 2021 (AOR 0.66 [95% CI 0.51 to 0.85] p-value = 0.004). Hispanic (versus non-Hispanic) ethnicity was associated with higher risk of SARS-CoV-2 infection and mortality during almost every time period, with no evidence of attenuation over time. Urban (versus rural) residence was associated with higher risk of infection (AOR 2.02, [95% CI 1.83 to 2.22], p-value < 0.001), mortality (AOR 2.48 [95% CI 2.08 to 2.96], p-value < 0.001), and case fatality (AOR 2.24, 95% CI 1.93 to 2.60, p-value < 0.001) in February to April 2020, but these associations attenuated over time and reversed by September 2020 (AOR 0.85, 95% CI 0.81 to 0.89, p-value < 0.001 for infection, AOR 0.72, 95% CI 0.62 to 0.83, p-value < 0.001 for mortality and AOR 0.81, 95% CI 0.71 to 0.93, p-value = 0.006 for case fatality). Throughout the observation period, high comorbidity burden, younger age, and obesity were consistently associated with infection, while high comorbidity burden, older age, and male sex were consistently associated with mortality. Limitations of the study include that changes over time in the associations of some risk factors may be affected by changes in the likelihood of testing for SARS-CoV-2 according to those risk factors; also, study results apply directly to VA enrollees who are predominantly male and have comprehensive healthcare and need to be confirmed in other populations. CONCLUSIONS: In this study, we found that strongly positive associations of Black and AI/AN (versus White) race and urban (versus rural) residence with SARS-CoV-2 infection, mortality, and case fatality observed early in the pandemic were ameliorated or reversed by March 2021.

Impact of Sustained Virologic Response with Direct-Acting Antiviral Treatment on Mortality in Patients with Advanced Liver Disease.

The impact of sustained virologic response (SVR) on mortality after direct-acting antiviral treatment is not well documented. This study evaluated the impact of direct-acting antiviral-induced SVR on all-cause mortality and on incident hepatocellular carcinoma (HCC) in 15,059 hepatitis C virus-infected patients with advanced liver disease defined by a FIB-4 >3.25. Overall, 1,067 patients did not achieve SVR (no SVR) and 13,992 patients achieved SVR. In a mean follow-up period of approximately 1.6 years, 195 no SVR patients and 598 SVR patients died. Mortality rates were 12.3 deaths/100 patient years of follow-up for no SVR patients and 2.6 deaths/100 patient years for SVR patients, a 78.9% reduction (P < 0.001). Among patients without a prior diagnosis of HCC, 140 no SVR patients and 397 SVR patients were diagnosed with incident HCC. HCC rates were 11.5 HCCs/100 patient years for no SVR patients and 1.9 HCCs/100 patient years for SVR patients, an 83.5% reduction (P < 0.001). In multivariable Cox proportional hazard models controlling for baseline demographics, clinical characteristics, and comorbidities, SVR was independently associated with reduced risk of death compared to no SVR (hazard ratio, 0.26; 95% confidence interval, 0.22-0.31; P < 0.001). A history of decompensated liver disease (hazard ratio, 1.57; 95% confidence interval, 1.34-1.83; P < 0.001) and decreased albumin (hazard ratio, 2.70 per 1 g/dL decrease; 95% confidence interval, 2.38-3.12; P < 0.001) were independently associated with increased risk of death. Conclusion: Those achieving SVR after direct-acting antiviral treatment had significantly lower all-cause mortality and lower incident HCC rates than those who did not achieve SVR.

Real-world effectiveness of daclatasvir plus sofosbuvir and velpatasvir/sofosbuvir in hepatitis C genotype 2 and 3.

BACKGROUND & AIM: Understanding the real-world effectiveness of all-oral hepatitis C virus (HCV) regimens informs treatment decisions. We evaluated the effectiveness of daclatasvir + sofosbuvir ±â€¯ribavirin (DCV + SOF ±â€¯RBV) and velpatasvir/sofosbuvir (VEL/SOF) ±â€¯RBV in patients with genotype 2 and genotype 3 infection treated in routine practice. METHODS: This observational analysis was carried out in an intent-to-treat cohort of patients with HCV genotype 2 and genotype 3. Sustained virologic response (SVR) analysis was performed in 5,400 patients initiated on DCV + SOF ±â€¯RBV or VEL/SOF ±â€¯RBV at any Department of Veterans Affairs facility. RESULTS: For genotype 2, SVR rates did not differ between DCV + SOF (94.5%) and VEL/SOF (94.4%) or between DCV + SOF + RBV (88.1%) and VEL/SOF + RBV (89.5%). For genotype 3, SVR rates did not differ between DCV + SOF (90.8%) and VEL/SOF (92.0%) or between DCV + SOF + RBV (88.1%) and VEL/SOF + RBV (86.4%). In multivariate models of patients with genotype 2 and 3 infection, the treatment regimen was not a significant predictor of the odds of SVR. For genotype 3, significant predictors of reduced odds of SVR were prior HCV treatment-experience (odds ratio [OR] 0.51, 95% CI 0.36-0.72; p <0.001), FIB-4 >3.25 (OR 0.60; 95%CI 0.43-0.84; p = 0.002) and a history of decompensated liver disease (OR 0.68; 95%CI 0.47-0.98; p = 0.04). For patients with genotype 2 and 3, treated with VEL/SOF ±â€¯RBV, 89% and 85% received 12-weeks of treatment, respectively. For DCV + SOF ±â€¯RBV, 56% and 20% of patients with HCV genotype 2 received 12-weeks and 24-weeks of treatment, respectively; while 53% and 23% of patients with HCV genotype 3 received 12-weeks and 24-weeks, with most direct-acting antiviral experienced patients receiving 24-weeks. CONCLUSIONS: In patients infected with HCV genotype 2 and 3, DCV + SOF ±â€¯RBV and VEL/SOF ±â€¯RBV produced similar SVR rates within each genotype, and the regimen did not have a significant impact on the odds of SVR. For patients with genotype 3, prior treatment-experience and advanced liver disease were significant predictors of reduced odds of SVR regardless of regimen. LAY SUMMARY: In clinical practice, cure rates for hepatitis C virus (HCV) genotype 2 were 94% and cure rates for HCV genotype 3 were 90%. The chance of achieving cure was the same whether a person received daclatasvir plus sofosbuvir or velpatasvir/sofosbuvir. Ribavirin did not affect cure rates. The chance of a cure was lowest in people who had received HCV medication in the past.

Real-world effectiveness of sofosbuvir/velpatasvir/voxilaprevir in 573 direct-acting antiviral experienced hepatitis C patients.

Sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) provides a needed hepatitis C virus (HCV) antiviral option for direct-acting antiviral (DAA)-experienced patients. We evaluated the effectiveness of SOF/VEL/VOX for 12 weeks in DAA-experienced patients with genotype 1-4 treated in clinical practice. In this observational cohort analysis from the Veterans Affairs' Clinical Case Registry, 573 DAA-experienced patients initiating SOF/VEL/VOX were included: 490 genotype 1, 20 genotype 2, 51 genotype 3 and 12 genotype 4. Rates of cirrhosis were 32.7%, 30.0%, 49.0% and 58.3%; rates of prior NS5A-experience were 100.0%, 95.0%, 90.2% and 100.0% for genotypes 1-4, respectively. Overall SVR rates were 90.7% (429/473), 90.0% (18/20), 91.3% (42/46) and 100.0% (12/12) for genotypes 1-4, respectively, and were 91.3% (274/300), 88.9% (16/18), 90.2% (37/41) and 100.0% (11/11) for those with prior NS5A + NS5B experience. For genotype 1, SVR rates were similar in patients with prior regimens of ledipasvir/SOF (90.6%, 298/329), elbasvir/grazoprevir (91.2%, 73/80) and ombitasvir/paritaprevir/ritonavir/dasabuvir (90.9%, 70/77). SVR rates in genotype 1, 2 and 3 patients with prior SOF/VEL experience were 78.9% (15/19), 86.7% (13/15) and 84.6% (11/13). In genotype 1-4 patients completing 12 weeks of SOF/VEL/VOX, overall SVR rates were 95.1% (409/430), 89.5% (17/19), 93.3% (42/45) and 100% (12/12). In this diverse real-world cohort of heavily NS5A pretreated patients, SOF/VEL/VOX SVR rates in DAA-experienced patients were high across all genotypes. Genotype 1 patients who had prior experience with the most commonly prescribed NS5A regimens achieved similarly high SVR rates when retreated with SOF/VEL/VOX. For genotypes 1, 2 and 3, patients with prior SOF/VEL experience had lower SVR rates.

Direct-acting antiviral sustained virologic response: Impact on mortality in patients without advanced liver disease.

The impact of sustained virologic response (SVR) on mortality after direct-acting antiviral (DAA) treatment is not well documented in patients without advanced liver disease and affects access to treatment. This study evaluated the impact of SVR achieved with interferon-free DAA treatment on all-cause mortality in hepatitis C virus-infected patients without advanced liver disease. This observational cohort analysis was comprised of 103,346 genotype 1, 2, and 3, hepatitis C virus-monoinfected patients without advanced liver disease, defined by FIB-4 ≤3.25 and no diagnosis of cirrhosis, hepatic decompensation, or hepatocellular carcinoma or history of liver transplantation, identified from the Veterans Affairs Hepatitis C Clinical Case Registry. Among 40,664 patients treated with interferon-free DAA regimens, 39,374 (96.8%) achieved SVR and 1,290 (3.2%) patients were No SVR; 62,682 patients constituted the untreated cohort. The mortality rate for SVR patients of 1.18 deaths/100 patient-years was significantly lower than the rates for both No SVR patients (2.84 deaths/100 patient-years; P < 0.001) and untreated patients (3.84 deaths/100 patient-years; P < 0.001). SVR patients with FIB-4 <1.45 and 1.45-3.25 had a 46.0% (P = 0.036) and 63.2% (P < 0.001) reduction in mortality rates, respectively, compared to No SVR patients and 66.7% (P < 0.001) and 70.6% (P < 0.001) reduction in mortality rates, respectively, compared to untreated patients. In multivariate Cox proportional hazard models controlling for baseline demographics, clinical characteristics, and comorbidities, SVR was independently associated with reduced risk of death compared to No SVR (hazard ratio, 0.44; 95% confidence interval, 0.32-0.59; P < 0.001) and compared to untreated patients (hazard ratio, 0.32; 95% confidence interval, 0.29-0.36; P < 0.001). CONCLUSION: Successfully treating hepatitis C virus with DAAs in patients without clinically apparent advanced liver disease translates into a significant mortality benefit. (Hepatology 2018).

Evaluation of hepatitis B reactivation among 62,920 veterans treated with oral hepatitis C antivirals.

Reactivation of hepatitis B virus (HBV) has been reported in hepatitis C virus-infected individuals receiving direct-acting antiviral (DAA) therapy. The overall risk among patients with current or prior HBV infection in the context of DAA treatment is unknown. The aim of this evaluation was to identify and characterize HBV reactivation among veterans treated with oral DAA therapy. This retrospective evaluation included 62,290 hepatitis C virus-infected veterans completing oral DAA treatment. Baseline HBV infection status for each veteran was identified from HBV laboratory data performed prior to DAA initiation. To assess for HBV reactivation and hepatitis we identified all hepatitis B surface antigen (HBsAg), HBV DNA, and alanine aminotransferase results obtained while on DAA treatment or 7 days after. HBV reactivation was defined as a >1000 IU/mL increase in HBV DNA or HBsAg detection in a person who was previously negative. Prior to DAA treatment 85.5% (53,784/62,920) had HBsAg testing and 0.70% (377/53,784) were positive; 84.6% (53,237/62,920) had a hepatitis B surface antibody test, of which 42.2% (22,479/53,237) were positive. In all, 9 of 62,290 patients treated with DAAs had evidence of HBV reactivation occurring while on DAA treatment. Eight occurred in patients known to be HBsAg-positive, and 1 occurred in a patient known to be isolated hepatitis B core antibody-positive. Seventeen other patients had small increases in HBV DNA levels that did not qualify as HBV reactivation. Only 3 of the 9 patients identified with HBV reactivation in this cohort exhibited peak alanine aminotransferase elevations >2 times the upper limit of normal. CONCLUSION: HBV reactivation of varying severity, even in the setting of isolated hepatitis B core antibody, with or without accompanying hepatitis can occur-though the occurrence of accompanying severe hepatitis was rare. (Hepatology 2017;66:27-36).

Effectiveness of All-Oral Antiviral Regimens in 996 Human Immunodeficiency Virus/Hepatitis C Virus Genotype 1-Coinfected Patients Treated in Routine Practice.

BACKGROUND.: Large cohorts are needed to assess human immunodeficiency virus (HIV)/hepatitis C virus (HCV) real-world treatment outcomes. We examined the effectiveness of ledipasvir/sofosbuvir with or without ribavirin (LDV/SOF ± RBV) and ombitasvir/ paritaprevir/ritonavir plus dasabuvir (OPrD) ± RBV in HIV/HCV genotype 1 (GT1)-coinfected patients initiating HCV therapy in clinical practice. METHODS.: Observational intent-to-treat cohort analysis using the Veterans Affairs Clinical Case Registry to identify HIV/HCV GT1-coinfected veterans initiating 12 weeks of LDV/SOF ± RBV or OPrD ± RBV. Multivariate models of sustained virologic response (SVR) included age, race, cirrhosis, proton pump inhibitor (PPI) prescription, prior HCV treatment, body mass index, genotype subtype, and HCV treatment regimen. RESULTS.: Nine hundred ninety-six HIV/HCV GT1-coinfected veterans initiated therapy: 757 LDV/SOF, 138 LDV/SOF + RBV, 28 OPrD, and 73 OPrD + RBV. Overall SVR was 90.9% (823/905); LDV/SOF 92.1% (631/685), LDV/SOF + RBV 86.3% (113/131), OPrD 88.9% (24/27), and OPrD + RBV 88.7% (55/62). SVR was 85.9% (176/205) and 92.4% (647/700) in those with and without cirrhosis (P = .006). SVR was similar between African Americans (90.5% [546/603]) and all others (91.7% [277/302]). PPI use with LDV/SOF ± RBV did not affect SVR (89.7% [131/146] with PPI and 91.5% [613/670] without PPI). Cirrhosis was predictive of reduced SVR (0.51 [95% confidence interval {CI}, .31-.87]; P = .01). Median creatinine change did not differ among patients receiving LDV/SOF and tenofovir disoproxil fumarate (TDF) without a protease inhibitor (PI) (0.18 [interquartile range {IQR}, 0.08-0.30]; n = 372), LDV/SOF and TDF/PI (0.17 [IQR, 0.04-0.30]; n = 100), and LDV/SOF without TDF (0.15 [IQR, 0.00-0.30]; n = 423). CONCLUSIONS.: SVR rates in HIV/HCV GT1-coinfected patients were high. African American race or PPI use with LDV/SOF ± RBV was not associated with lower SVR rates, but cirrhosis was. Renal function did not worsen on LDV/SOF regimens with TDF.

Prevalence of Human Immunodeficiency Virus, Hepatitis C Virus, and Hepatitis B Virus Among Homeless and Nonhomeless United States Veterans.

BACKGROUND: Veterans are disproportionately affected by human immunodeficiency virus (HIV), hepatitis C virus (HCV), and hepatitis B virus (HBV). Homeless veterans are at particularly high risk for HIV, HCV, and HBV due to a variety of overlapping risk factors, including high rates of mental health disorders and substance use disorders. The prevalence of HIV, HCV, and HBV among homeless veterans nationally is currently unknown. This study describes national testing rates and prevalence of HIV, HCV, and HBV among homeless veterans. METHODS: Using data from the Department of Veterans Affairs (VA) Corporate Warehouse Data from 2015, we evaluated HIV, HCV, and HBV laboratory testing and infection confirmation rates and diagnoses on the Problem List for nonhomeless veterans and for veterans utilizing homeless services in 2015. RESULTS: Among 242740 homeless veterans in VA care in 2015, HIV, HCV, and HBV testing occurred in 63.8% (n = 154812), 78.1% (n = 189508), and 52.8% (n = 128262), respectively. The HIV population prevalence was 1.52% (3684/242740) among homeless veterans, compared with 0.44% (23797/5424685) among nonhomeless veterans. The HCV population prevalence among homeless veterans was 12.1% (29311/242740), compared with 2.7% (148079/5424685) among nonhomeless veterans, while the HBV population prevalence was 0.99% (2395/242740) for homeless veterans and 0.40% (21611/5424685) among nonhomeless veterans. CONCLUSIONS: To our knowledge this work represents the most comprehensive tested prevalence and population prevalence estimates of HIV, HCV, and HBV among homeless veterans nationally. The data demonstrate high prevalence of HIV, HCV, and HBV among homeless veterans, and reinforce the need for integrated healthcare services along with homeless programming.

Real-world effectiveness of ledipasvir/sofosbuvir in 4,365 treatment-naive, genotype 1 hepatitis C-infected patients.

UNLABELLED: Real-world effectiveness data are needed to inform hepatitis C virus (HCV) treatment decisions. The uptake of ledipasvir/sofosbuvir (LDV/SOF) regimens across health care settings has been rapid, but variations often occur in clinical practice. The aim of this study was to assess sustained virologic response (SVR) of LDV/SOF±ribavirin (RBV) in routine medical practice. This observational, intent-to-treat cohort was comprised of 4,365 genotype 1, treatment-naive, HCV-infected veterans treated with LDV/SOF±RBV. SVR rates were 91.3% (3,191/3,495) for LDV/SOF and 92.0% (527/573) for LDV/SOF+RBV (P = 0.65). African American race (odds ratio 0.70, 95% confidence interval 0.54-0.90, P = 0.004) and FIB-4 >3.25 (odds ratio 0.56, 95% confidence interval 0.43-0.71, P < 0.001) were independently associated with decreased likelihood of SVR; age, sex, body mass index, decompensated liver disease, diabetes, genotype 1 subtype, and regimen did not predict SVR. In models limited to those who completed 12 weeks of treatment, African American race was no longer a significant predictor of SVR but FIB-4 >3.25 (odds ratio 0.35, 95% confidence interval 0.24-0.50, P < 0.001) remained. Among those without cirrhosis (defined by FIB-4 ≤3.25) and with baseline HCV RNA<6,000,000 IU/mL, SVR rates were 93.2% (1,020/1,094) for those who completed 8 weeks of therapy and 96.6% (875/906) for those who completed 12 weeks of therapy (P = 0.001). CONCLUSIONS: In this real-world cohort, SVR rates with LDV/SOF±RBV nearly matched the rates reported in clinical trials and were consistently high across all subgroups; those without cirrhosis but with HCV RNA<6,000,000 IU/mL were less likely to achieve SVR with 8 weeks compared to 12 weeks of therapy, although the numeric difference in SVR rates was small. (Hepatology 2016;64:405-414).

Cascade of Care for Hepatitis C Virus Infection Within the US Veterans Health Administration.

OBJECTIVES: We measured the quality of HCV care using a cascade of HCV care model. METHODS: We estimated the number of patients diagnosed with chronic HCV, linked to HCV care, treated with HCV antivirals, and having achieved a sustained virologic response (SVR) in the electronic medical record data from the Veterans Health Administration's Corporate Data Warehouse and the HCV Clinical Case Registry in 2013. RESULTS: Of the estimated 233,898 patients with chronic HCV, 77% (181,168) were diagnosed, 69% (160,794) were linked to HCV care, 17% (39,388) were treated with HCV antivirals, and 7% (15,983) had achieved SVR. CONCLUSIONS: This Cascade of HCV Care provides a clinically relevant model to measure the quality of HCV care within a health care system and to compare HCV care across health systems.

Cigarette Smoking, Reduction and Quit Attempts: Prevalence Among Veterans With Coronary Heart Disease.

INTRODUCTION: Cigarette smoking increases the risk of illness and early death for people with coronary heart disease. In 2010, Brown estimated prevalence rates for smoking among veterans and nonveterans with or without coronary heart disease in the United States, based on the 2003 through 2007 data from the Behavioral Risk Factor Surveillance System (BRFSS). Recent changes in BRFSS methods promise more accurate estimates for veterans. To inform assessment of efforts to reduce smoking, we sought to provide prevalence rates for smoking behaviors among US veterans with coronary heart disease and to compare rates for veterans with those for civilians. METHODS: We conducted a cross-sectional analysis of participants who responded to BRFSS from 2009 to 2012. Accounting for complex BRFSS sampling, we estimated national prevalence rates by sex for smoking status, frequency, and quit attempts; for those with and those without coronary heart disease; for civilians; for veterans and active duty personnel combined; and, after adjusting for BRFSS mingling of active duty personnel and veterans, for veterans only. We examined differences between veterans and civilians by using age-standardized national estimates. RESULTS: Among men with coronary heart disease, more veterans than civilians smoked and more were daily smokers, but veterans were no more likely to attempt to quit. Among women with coronary heart disease, we found no differences between civilians and veterans. CONCLUSION: Cigarette smoking is more prevalent among male veterans with coronary heart disease than among their civilian counterparts. Not distinguishing active duty personnel from veterans can materially affect prevalence estimates intended to apply solely to veterans.

Impact of provider type on hepatitis C outcomes with boceprevir-based and telaprevir-based regimens.

GOALS: To examine the effect of provider type on outcomes and safety in a large hepatitis C virus (HCV)-infected cohort treated in routine medical practice. BACKGROUND: Nonphysician providers (NPP) are uniquely positioned to expand health care infrastructure to meet HCV treatment demands. STUDY: Retrospective, observational cohort analysis of 820 HCV genotype 1-infected veterans initiated on peginterferon/ribavirin and boceprevir or telaprevir in routine medical practice at 94 VA facilities before January 1, 2012 and followed through July 30, 2013. Provider type was determined from prescription records and included physicians (MD) or NPPs (ie, nurse practitioners, physician assistants, and pharmacists). Inverse probability-of-treatment weighting and unweighted logistic regression analysis was used for comparison of sustained virologic response (SVR), treatment discontinuation rates, and adverse hematologic events. RESULTS: There was no significant difference in SVR by provider type overall (NPPs 52% vs. MDs 49%, P=0.33) and within patient subgroups, or in treatment discontinuation rates. In multivariate analyses, provider type was not associated with any significant difference in the odds of achieving SVR (NPP vs. MD; odds ratio 1.17; 95% confidence interval, 0.84-1.63; P=0.37 inverse probability of treatment weighting; odds ration 1.16, 95% confidence interval, 0.84-1.59, P=0.38 unweighted). Hematologic adverse event rates were similar: anemia: 57% NPP, 62% MD; thrombocytopenia: 43% NPP, 40% MD; neutropenia: 40% NPP, 39% MD. CONCLUSIONS: Treatment prescribed by NPPs was as likely to result in SVR as treatment prescribed by MDs, even after accounting for patient differences. Engaging more NPPs as HCV treatment providers may allow wider access to HCV treatment.

Impact of race/ethnicity and gender on HCV screening and prevalence among U.S. veterans in Department of Veterans Affairs Care.

OBJECTIVES: We assessed HCV screening and prevalence among veterans and estimated the potential impact of complete birth cohort screening, accounting for the disparate HCV disease burden by race/ethnicity and gender. METHODS: We used the Department of Veterans Affairs (VA) Corporate Data Warehouse to identify birth dates, gender, race/ethnicity, and laboratory tests for veterans with at least 1 VA outpatient visit in 2012. We calculated HCV screening rates, prevalence, and HCV infection incident diagnosis. RESULTS: Among 5,499,743 veterans, 54.7% had HCV screening through the VA. In more than 2.9 million veterans screened, HCV prevalence was 6.1% overall and highest among Blacks (11.8%), particularly Black men born in 1945 to 1965 (17.7%). HCV infection incident diagnosis in 2012 was 5.9% for men and 2.3% for women. An estimated additional 48,928 male veterans, including 12,291 Black men, and 1484 female veterans would potentially be identified as HCV infected with full birth cohort screening. CONCLUSIONS: HCV prevalence was markedly elevated among veterans born in 1945 to 1965, with substantial variation by race/ethnicity and gender. Full adoption of birth cohort screening may reveal substantial numbers of veterans with previously unknown HCV infection.

Association of distance from a transplant center with access to waitlist placement, receipt of liver transplantation, and survival among US veterans.

IMPORTANCE: Centralization of specialized health care services such as organ transplantation and bariatric surgery is advocated to improve quality, increase efficiency, and reduce cost. The effect of increased travel on access and outcomes from these services is not fully understood. OBJECTIVE: To evaluate the association between distance from a Veterans Affairs (VA) transplant center (VATC) and access to being waitlisted for liver transplantation, actually having a liver transplant, and mortality. DESIGN, SETTING, AND PARTICIPANTS: Retrospective study of veterans meeting liver transplantation eligibility criteria from January 1, 2003, until December 31, 2010, using data from the Veterans Health Administration's integrated, national, electronic medical record linked to Organ Procurement and Transplantation Network data. MAIN OUTCOMES AND MEASURES: The primary outcome was being waitlisted for transplantation at a VATC. Secondary outcomes included being waitlisted at any transplant center, undergoing a transplantation, and survival. RESULTS: From 2003-2010, 50,637 veterans were classified as potentially eligible for transplant; 2895 (6%) were waitlisted and 1418 of those were waitlisted (49%) at 1 of the 5 VATCs. Of 3417 veterans receiving care at a VA hospital located within 100 miles from a VATC, 244 (7.1%) were waitlisted at a VATC and 372 (10.9%) at any transplant center (VATC and non-VATCs). Of 47,219 veterans receiving care at a VA hospital located more than 100 miles from a VATC, 1174 (2.5%) were waitlisted at a VATC and 2523 (5.3%) at any transplant center (VATC and non-VATCs). In multivariable models, increasing distance to closest VATC was associated with significantly lower odds of being waitlisted at a VATC (odds ratio [OR], 0.91 [95% CI, 0.89-0.93] for each doubling in distance) or any transplant center (OR, 0.94 [95% CI, 0.92-0.96] for each doubling in distance). For example, a veteran living 25 miles from a VATC would have a 7.4% (95% CI, 6.6%-8.1%) adjusted probability of being waitlisted, whereas a veteran 100 miles from a VATC would have a 6.2% (95% CI, 5.7%-6.6%) adjusted probability. In adjusted models, increasing distance from a VATC was associated with significantly lower transplantation rates (subhazard ratio, 0.97; 95% CI, 0.95-0.98 for each doubling in distance). There was significantly increased mortality among waitlisted veterans from the time of first hepatic decompensation event in multivariable survival models (hazard ratio, 1.03; 95% CI, 1.01-1.04 for each doubling in distance). For example, a waitlisted veteran living 25 miles from a VATC would have a 62.9% (95% CI, 59.1%-66.1%) 5-year adjusted probability of survival from first hepatic decompensation event compared with a 59.8% (95% CI, 56.3%-63.1%) 5-year adjusted probability of survival for a veteran living 100 miles from a VATC. CONCLUSIONS AND RELEVANCE: Among VA patients meeting eligibility criteria for liver transplantation, greater distance from a VATC or any transplant center was associated with lower likelihood of being waitlisted, receiving a liver transplant, and greater likelihood of death. The relationship between these findings and centralizing specialized care deserves further investigation.

Early virologic responses and hematologic safety of direct-acting antiviral therapies in veterans with chronic hepatitis C.

BACKGROUND & AIMS: There are limited data on the early effectiveness of direct-acting antiviral (DAA) therapies for patients with hepatitis C virus (HCV) infection in routine medical practice. We aimed to evaluate real-world experience with DAA-based regimens. METHODS: By using the Veterans Affairs' Clinical Case Registry, we conducted a prospective observational intent-to-treat analysis of veterans infected with HCV genotype 1 who began treatment with pegylated interferon, ribavirin, and boceprevir (BOC, n = 661) or telaprevir (TVR, n = 198) before January 2012. We determined rates of virologic response at treatment weeks 4, 8, 12, and 24; futility; early discontinuation; and adverse hematologic events. RESULTS: About one third of patients discontinued treatment by week 24 (30% BOC, 34% TVR). A higher percentage of treatment-naive, noncirrhotic patients receiving BOC had undetectable levels of virus at week 24 than patients receiving TVR (74% vs 60%; P = .03). There were no significant differences in rates of early response within subgroups of cirrhotic patients, prior relapsers, prior partial responders, or prior null responders. By week 24, treatment was determined to be futile for 14% of patients receiving BOC and 17% of those receiving TVR. No differences were observed in overall rates of anemia (50% BOC, 49% TVR) or thrombocytopenia (16% BOC, 18% TVR); higher rates of neutropenia were observed in BOC-treated patients (34% BOC, 21% TVR; P = .008). CONCLUSIONS: HCV-infected veterans treated in routine medical practice with DAA-based regimens (BOC or TVR) had rates of early response comparable with those reported in clinical trials. However, they had higher rates of futility and early discontinuation than clinical trial participants. Further studies are needed to determine rates of sustained viral response.

Assessment and utilization of rapid virologic response in US veterans with chronic hepatitis C: evaluating provider adherence to practice guidelines.

BACKGROUND AND GOALS: There are limited data on the extent to which medical providers adhere to practice guidelines for the antiviral treatment of patients with chronic hepatitis C virus (HCV) infection. As representative of overall provider adherence to practice guidelines, provider adherence to specific recommendations regarding rapid virologic response (RVR) was assessed. STUDY: From the Department of Veterans Affairs' Clinical Case Registry, all patients with HCV genotype 1 who initiated peginterferon and ribavirin between January 1, 2007 and December 31, 2008 were identified. The rate of testing for RVR was determined. Patient, provider, and facility characteristics were assessed to determine the factors that predicted improved provider adherence. For patients who achieved RVR, the overall treatment duration was calculated as a secondary measure of provider adherence. RESULTS: About one half of the cohort (54%) had HCV RNA testing for RVR. Among several significant predictors, testing for RVR was more likely in gastroenterology/hepatology specialty clinics, by midlevel providers such as nurse practitioners and physician assistants, and in facilities with a higher volume of HCV patients. Most patients who achieved RVR completed a treatment course within the recommended range. However, 27% of the cohort received more or less than the recommended duration of treatment, thereby unnecessarily increasing their risk for adverse events or decreasing their potential for cure. CONCLUSIONS: More aggressive education is needed to improve provider adherence to HCV antiviral treatment guidelines and optimize the outcomes of HCV patients, especially with the recent approval of complicated direct-acting antiviral regimens.

A sustained virologic response reduces risk of all-cause mortality in patients with hepatitis C.

BACKGROUND & AIMS: The effectiveness of hepatitis C virus (HCV) treatment with pegylated interferon and ribavirin usually is evaluated by the surrogate end point of sustained virologic response (SVR), although the ultimate goal of antiviral treatment is to reduce mortality. The impact of SVR on all-cause mortality is not well documented by HCV genotype or in populations in routine medical practice with substantial comorbidities. METHODS: From the US Department of Veterans Affairs (VA), we identified all patients infected with HCV genotypes 1, 2, or 3, without human immunodeficiency virus co-infection or hepatocellular carcinoma before HCV treatment with pegylated interferon and ribavirin, who started HCV treatment from January 2001 to June 2007, stopped treatment by June 2008, and had a posttreatment HCV RNA test result of SVR or no SVR. Mortality data from VA and non-VA sources were available through 2009. RESULTS: HCV genotypes 1, 2, or 3 cohorts consisted of 12,166, 2904, and 1794 patients, respectively, with SVR rates of 35%, 72%, and 62%, respectively. Each cohort had high rates of comorbidities. During a median follow-up period of approximately 3.8 years, 1119 genotype-1, 220 genotype-2, and 196 genotype-3 patients died. In genotype-specific multivariate survival models that controlled for demographic factors, comorbidities, laboratory characteristics, and treatment characteristics, an SVR was associated with substantially reduced mortality risk for each genotype (genotype-1 hazard ratio, 0.70; P < .0001; genotype-2 hazard ratio, 0.64; P = .006; genotype-3 hazard ratio, 0.51; P = .0002). CONCLUSIONS: An SVR reduced mortality among patients infected with HCV of genotypes 1, 2, or 3 who were being treated by routine medical practice and had substantial comorbidities.

Development of COVIDVax Model to Estimate the Risk of SARS-CoV-2-Related Death Among 7.6 Million US Veterans for Use in Vaccination Prioritization.

Importance: A strategy that prioritizes individuals for SARS-CoV-2 vaccination according to their risk of SARS-CoV-2-related mortality would help minimize deaths during vaccine rollout. Objective: To develop a model that estimates the risk of SARS-CoV-2-related mortality among all enrollees of the US Department of Veterans Affairs (VA) health care system. Design, Setting, and Participants: This prognostic study used data from 7 635 064 individuals enrolled in the VA health care system as of May 21, 2020, to develop and internally validate a logistic regression model (COVIDVax) that predicted SARS-CoV-2-related death (n = 2422) during the observation period (May 21 to November 2, 2020) using baseline characteristics known to be associated with SARS-CoV-2-related mortality, extracted from the VA electronic health records (EHRs). The cohort was split into a training period (May 21 to September 30) and testing period (October 1 to November 2). Main Outcomes and Measures: SARS-CoV-2-related death, defined as death within 30 days of testing positive for SARS-CoV-2. VA EHR data streams were imported on a data integration platform to demonstrate that the model could be executed in real-time to produce dashboards with risk scores for all current VA enrollees. Results: Of 7 635 064 individuals, the mean (SD) age was 66.2 (13.8) years, and most were men (7 051 912 [92.4%]) and White individuals (4 887 338 [64.0%]), with 1 116 435 (14.6%) Black individuals and 399 634 (5.2%) Hispanic individuals. From a starting pool of 16 potential predictors, 10 were included in the final COVIDVax model, as follows: sex, age, race, ethnicity, body mass index, Charlson Comorbidity Index, diabetes, chronic kidney disease, congestive heart failure, and Care Assessment Need score. The model exhibited excellent discrimination with area under the receiver operating characteristic curve (AUROC) of 85.3% (95% CI, 84.6%-86.1%), superior to the AUROC of using age alone to stratify risk (72.6%; 95% CI, 71.6%-73.6%). Assuming vaccination is 90% effective at preventing SARS-CoV-2-related death, using this model to prioritize vaccination was estimated to prevent 63.5% of deaths that would occur by the time 50% of VA enrollees are vaccinated, significantly higher than the estimate for prioritizing vaccination based on age (45.6%) or the US Centers for Disease Control and Prevention phases of vaccine allocation (41.1%). Conclusions and Relevance: In this prognostic study of all VA enrollees, prioritizing vaccination based on the COVIDVax model was estimated to prevent a large proportion of deaths expected to occur during vaccine rollout before sufficient herd immunity is achieved.