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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.
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COVID-19/mortalidad , Vigilancia de la Población , Grupos Raciales , Población Rural/tendencias , United States Department of Veterans Affairs/tendencias , Población Urbana/tendencias , Anciano , COVID-19/diagnóstico , COVID-19/economía , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mortalidad/tendencias , Vigilancia de la Población/métodos , Factores de Riesgo , Factores Socioeconómicos , Estados Unidos/epidemiologíaRESUMEN
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 7â¯635â¯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 7â¯635â¯064 individuals, the mean (SD) age was 66.2 (13.8) years, and most were men (7â¯051â¯912 [92.4%]) and White individuals (4â¯887â¯338 [64.0%]), with 1â¯116â¯435 (14.6%) Black individuals and 399â¯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.
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Vacunas contra la COVID-19/uso terapéutico , COVID-19/prevención & control , Planificación en Salud/métodos , Prioridades en Salud/estadística & datos numéricos , Vacunación Masiva , Veteranos/estadística & datos numéricos , Anciano , Área Bajo la Curva , Comorbilidad , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Pronóstico , Curva ROC , Medición de Riesgo , Factores de Riesgo , SARS-CoV-2 , Estados UnidosRESUMEN
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.
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Antivirales/uso terapéutico , Carbamatos/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Compuestos Heterocíclicos de 4 o más Anillos/uso terapéutico , Compuestos Macrocíclicos/uso terapéutico , Sofosbuvir/uso terapéutico , Sulfonamidas/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Combinación de Medicamentos , Sustitución de Medicamentos , Femenino , Genotipo , Hepacivirus/genética , Hepatitis C Crónica/epidemiología , Hepatitis C Crónica/virología , Humanos , Masculino , Persona de Mediana Edad , Respuesta Virológica Sostenida , Estados Unidos/epidemiología , Servicios de Salud para Veteranos/estadística & datos numéricos , Proteínas no Estructurales Virales/antagonistas & inhibidoresRESUMEN
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.
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Antivirales/uso terapéutico , Hepatitis C/tratamiento farmacológico , Respuesta Virológica Sostenida , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Hepatitis C/mortalidad , Hepatitis C/virología , Humanos , Masculino , Persona de Mediana Edad , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND & AIM: Understanding the real-world effectiveness of all-oral hepatitis C virus (HCV) regimens informs treatment decisions. We evaluated the effectiveness of daclatasvirâ¯+â¯sofosbuvir⯱â¯ribavirin (DCVâ¯+â¯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 DCVâ¯+â¯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 DCVâ¯+â¯SOF (94.5%) and VEL/SOF (94.4%) or between DCVâ¯+â¯SOFâ¯+â¯RBV (88.1%) and VEL/SOFâ¯+â¯RBV (89.5%). For genotype 3, SVR rates did not differ between DCVâ¯+â¯SOF (90.8%) and VEL/SOF (92.0%) or between DCVâ¯+â¯SOFâ¯+â¯RBV (88.1%) and VEL/SOFâ¯+â¯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; pâ¯=â¯0.002) and a history of decompensated liver disease (OR 0.68; 95%CI 0.47-0.98; pâ¯=â¯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 DCVâ¯+â¯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, DCVâ¯+â¯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.
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Carbamatos/uso terapéutico , ADN Viral/genética , Hepacivirus/genética , Hepatitis C Crónica/tratamiento farmacológico , Compuestos Heterocíclicos de 4 o más Anillos/uso terapéutico , Imidazoles/uso terapéutico , Sistema de Registros , Sofosbuvir/uso terapéutico , Antivirales/uso terapéutico , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Genotipo , Hepatitis C Crónica/virología , Humanos , Masculino , Persona de Mediana Edad , Pirrolidinas , Estudios Retrospectivos , Resultado del Tratamiento , Valina/análogos & derivadosRESUMEN
In direct acting antiviral (DAA)-treated HCV genotype 1, the sustained virologic response rate with the ∆G/∆G genotype of IFNL4 rs368234815 (86.8%) was significantly lower than with ∆G/TT (95.9%, P = 0.03) or TT/TT (98.6%, P = 0.01). The SVR odds ratio for ∆G/∆G compared to TT/TT was 0.10 (P = 0.03). IFNL4 genotype might predict DAA-response.
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Antivirales/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/genética , Interleucinas/genética , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Respuesta Virológica SostenidaRESUMEN
The Department of Veterans Affairs (VA) has made significant progress in treating hepatitis C virus, experiencing more than a 75% reduction in veterans remaining to be treated since the availability of oral direct-acting antivirals. Hepatitis C Innovation Teams use lean process improvement and system redesign, resulting in practice models that address gaps in care. The key to success is creative improvements in veteran access to providers, including expanded use of nonphysician providers, video telehealth, and electronic technologies. Population health management tools monitor and identify trends in care, helping the VA tailor care and address barriers.
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Hepatitis C/tratamiento farmacológico , Hepatitis C/epidemiología , United States Department of Veterans Affairs , Salud de los Veteranos , Antivirales/uso terapéutico , Manejo de la Enfermedad , Hepacivirus/efectos de los fármacos , Hepatitis C/diagnóstico , Hepatitis C/virología , Humanos , Telemedicina , Estados Unidos/epidemiología , Veteranos/estadística & datos numéricosRESUMEN
BACKGROUND: Direct-acting antiviral (DAA) therapy for chronic hepatitis C virus (HCV) infection might pose a risk for hepatitis B virus (HBV) reactivation in patients coinfected with chronic or resolved HBV infection. The need for HBV antiviral prophylaxis during DAA treatment remains controversial. We aimed to analyse the absolute risk of HBV reactivation in patients with active or resolved HBV infection treated with DAAs for HCV infection. METHODS: For this systematic review and meta-analysis, we searched PubMed, Ovid MEDLINE, the Cochrane Central Register of Controlled Trials, and Web of Science from Oct 1, 2010, to Sept 30, 2017, to identify studies of patients with chronic or resolved HBV infection at baseline treated with DAAs for chronic HCV infection. Conference proceedings, abstract books, and references from relevant reviews were also examined for potential studies. Two independent researchers extracted data and assessed quality and risk of bias. Data were pooled by use of random-effects models. The primary outcome was HBV reactivation defined by standardised nomenclature. This study is registered with PROSPERO, number CRD42017065882. FINDINGS: We identified 17 observational studies involving 1621 patients with chronic (n=242) or resolved (n=1379) HBV infection treated with different DAAs. The pooled proportion of patients who had HBV reactivation was 24% (95% CI 19-30) in patients with chronic HBV infection and 1·4% (0·8-2·4) in those with resolved HBV infection. In patients with chronic HBV infection, the pooled proportion of patients with HBV-reactivation-related hepatitis was 9% (95% CI 5-16) and the relative risk (RR) of HBV-reactivation-related hepatitis was significantly lower in patients with HBV DNA below the lower limit of quantification at baseline than in those with quantifiable HBV DNA (RR 0·17, 95% CI 0·06-0·50; p=0·0011). Three major clinical events related to HBV reactivation in patients with chronic HBV infection were reported (one patient had liver decompensation and two had liver failure, one of whom required liver transplantation). In patients with resolved HBV infection, no HBV-reactivation-related hepatitis was reported. INTERPRETATION: HBV reactivation occurs frequently in patients with chronic HBV and HCV coinfection receiving DAA therapy but is rare among patients with resolved HBV infection. Use of antiviral prophylaxis might be warranted in patients who test positive for hepatitis B surface antigen (HBsAg), particularly those with quantifiable HBV DNA. FUNDING: None.
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Antivirales/uso terapéutico , Virus de la Hepatitis B/fisiología , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/virología , Activación Viral , Coinfección , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/virología , Hepatitis C Crónica/complicaciones , Humanos , Interferones/uso terapéuticoRESUMEN
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).
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Antivirales/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/mortalidad , Respuesta Virológica Sostenida , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
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.
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Infecciones por VIH/epidemiología , Hepatitis B/epidemiología , Hepatitis C/epidemiología , Personas con Mala Vivienda , Veteranos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , VIH/aislamiento & purificación , Infecciones por VIH/diagnóstico , Infecciones por VIH/virología , Hepacivirus/aislamiento & purificación , Hepatitis B/diagnóstico , Hepatitis B/virología , Virus de la Hepatitis B/aislamiento & purificación , Hepatitis C/diagnóstico , Hepatitis C/virología , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Factores de Riesgo , Trastornos Relacionados con Sustancias/epidemiología , Estados Unidos/epidemiologíaRESUMEN
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).
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Antivirales/uso terapéutico , Coinfección/virología , Hepatitis B/fisiopatología , Hepatitis C/tratamiento farmacológico , Activación Viral/efectos de los fármacos , Administración Oral , Adulto , Estudios de Cohortes , Coinfección/epidemiología , Femenino , Estudios de Seguimiento , Hepacivirus/efectos de los fármacos , Hepatitis B/epidemiología , Antígenos de Superficie de la Hepatitis B/inmunología , Virus de la Hepatitis B/efectos de los fármacos , Virus de la Hepatitis B/aislamiento & purificación , Hepatitis C/diagnóstico , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Medición de Riesgo , VeteranosRESUMEN
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.
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Antivirales/uso terapéutico , Coinfección/tratamiento farmacológico , Infecciones por VIH/tratamiento farmacológico , Hepacivirus/genética , Hepatitis C/tratamiento farmacológico , Administración Oral , Anciano , Anilidas/administración & dosificación , Anilidas/uso terapéutico , Antivirales/administración & dosificación , Bencimidazoles/administración & dosificación , Bencimidazoles/uso terapéutico , Carbamatos/administración & dosificación , Carbamatos/uso terapéutico , Estudios de Cohortes , Coinfección/virología , Ciclopropanos , Quimioterapia Combinada , Femenino , Fluorenos/administración & dosificación , Fluorenos/uso terapéutico , Genotipo , Infecciones por VIH/complicaciones , Infecciones por VIH/virología , Hepacivirus/efectos de los fármacos , Hepatitis C/complicaciones , Hepatitis C/virología , Humanos , Lactamas Macrocíclicas , Compuestos Macrocíclicos/administración & dosificación , Compuestos Macrocíclicos/uso terapéutico , Masculino , Persona de Mediana Edad , Pautas de la Práctica en Medicina , Prolina/análogos & derivados , Sistema de Registros , Ribavirina/administración & dosificación , Ribavirina/uso terapéutico , Sofosbuvir/administración & dosificación , Sofosbuvir/uso terapéutico , Sulfonamidas , Respuesta Virológica Sostenida , Resultado del Tratamiento , Uridina Monofosfato/administración & dosificación , Uridina Monofosfato/análogos & derivados , Uridina Monofosfato/uso terapéutico , Valina , VeteranosRESUMEN
The Veterans Health Administration (VHA) is the largest provider of hepatitis C virus (HCV) care nationally and provides health care to >200 000 homeless veterans each year. We used the VHA's Corporate Data Warehouse and HCV Clinical Case Registry to evaluate engagement in the HCV care cascade among homeless and nonhomeless veterans in VHA care in 2015. We estimated that, among 242 740 homeless veterans in care and 5 424 712 nonhomeless veterans in care, 144 964 (13.4%) and 188 156 (3.5%), respectively, had chronic HCV infection. Compared with nonhomeless veterans, homeless veterans were more likely to be diagnosed with chronic HCV infection and linked to HCV care but less likely to have received antiviral therapy despite comparable sustained virologic response rates. Homelessness should not necessarily preclude HCV treatment eligibility with available all-oral antiviral regimens.
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Hepatitis C Crónica/terapia , Personas con Mala Vivienda , United States Department of Veterans Affairs , Veteranos , Anciano , Bases de Datos Factuales , Hepatitis C Crónica/epidemiología , Humanos , Persona de Mediana Edad , Estados Unidos/epidemiología , United States Department of Veterans Affairs/estadística & datos numéricosAsunto(s)
Anticuerpos contra la Hepatitis C , Veteranos , Hepacivirus , Hepatitis C , Humanos , Estados UnidosRESUMEN
BACKGROUND: Predictors of sustained virological response (SVR) to all-oral HCV regimens can inform nuanced treatment decisions. We evaluated effectiveness and identified predictors of SVR for ledipasvir/sofosbuvir ± ribavirin (LDV/SOF ±RBV) and ombitasvir/paritaprevir/ritonavir + dasabuvir (OPrD) ±RBV in patients treated in routine practice. METHODS: Observational, intent-to-treat cohort of 21,142 genotype-1 patients initiating 8 or 12 weeks of LDV/SOF ±RBV or 12 weeks of OPrD ±RBV at any Veterans Affairs facility. Multivariate logistic regression models were constructed to model SVR and identify predictors. RESULTS: SVR was 91.2% (9,781/10,720) for LDV/SOF, 89.6% (3,266/3,646) for LDV/SOF+RBV, 91.7% (1,197/1,306) for OPrD and 87.8% (3,365/3,832) for OPrD+RBV. For LDV/SOF ±RBV, reduced odds of SVR occurred in African-Americans (0.80, 95% CI 0.70, 0.92, P<0.001), body mass index (BMI)<25 (0.77, 95% CI 0.66, 0.90, P<0.001), BMI≥30 (0.77, 95% CI 0.67, 0.89, P<0.001), proton pump inhibitors (PPIs; 0.81, 95% CI 0.71, 0.92, P<0.001), decompensated liver disease (0.58, 95% CI 0.45, 0.74, P<0.001) and FIB4>3.25 (0.60, 95% CI 0.53, 0.69, P<0.001). For OPrD ±RBV, FIB-4>3.25 negatively predicted SVR (0.72, 95% CI 0.59, 0.88, P<0.001). Detectable 4-week on-treatment HCV RNA≥15 IU/ml reduced SVR odds for both regimens (LDV/SOF ±RBV OR 0.49, 95% CI 0.41, 0.58, P<0.001; OPrD ±RBV OR 0.38, 95% CI 0.29, 0.50, P<0.001). Receipt of OPrD+RBV compared to LDV/SOF reduced odds of SVR (OR 0.70, 95% CI 0.62, 0.80, P<0.001). Mental health diagnosis did not impact likelihood of SVR. CONCLUSIONS: The diversity and size of this cohort allowed for extensive examination of regimen-specific predictors of SVR. FIB-4>3.25 and detectable 4-week on-treatment HCV RNA had the greatest negative impact. African-American race, low or high BMI, and PPIs negatively impacted odds of SVR for LDV/SOF ±RBV. Mental health diagnoses did not.
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Antivirales/uso terapéutico , Genotipo , Hepacivirus/genética , Hepatitis C/tratamiento farmacológico , Hepatitis C/virología , Administración Oral , Adulto , Anciano , Anciano de 80 o más Años , Antivirales/administración & dosificación , Comorbilidad , Quimioterapia Combinada , Femenino , Hepatitis C/diagnóstico , Hepatitis C/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Factores de Riesgo , Respuesta Virológica Sostenida , Resultado del TratamientoRESUMEN
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).
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Antivirales/uso terapéutico , Bencimidazoles/uso terapéutico , Fluorenos/uso terapéutico , Hepatitis C/tratamiento farmacológico , Uridina Monofosfato/análogos & derivados , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Hepacivirus/genética , Hepatitis C/virología , Humanos , Masculino , Persona de Mediana Edad , Sofosbuvir , Resultado del Tratamiento , Uridina Monofosfato/uso terapéuticoRESUMEN
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.
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Enfermedad de la Arteria Coronaria/epidemiología , Cese del Hábito de Fumar/estadística & datos numéricos , Fumar/epidemiología , Veteranos/estadística & datos numéricos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Sistema de Vigilancia de Factor de Riesgo Conductual , Estudios Transversales , Femenino , Conductas Relacionadas con la Salud , Humanos , Masculino , Persona de Mediana Edad , Asunción de Riesgos , Factores Sexuales , Estados Unidos , Adulto JovenRESUMEN
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.
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Antivirales/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Genotipo , Hepacivirus/aislamiento & purificación , Hepatitis C Crónica/epidemiología , Humanos , Persona de Mediana Edad , Prevalencia , Sistema de Registros , Estados Unidos/epidemiología , United States Department of Veterans Affairs , VeteranosRESUMEN
OBJECTIVES: We described differences in demographic and socioeconomic characteristics between Veterans enrolled in the Veterans Health Administration (VHA) and Veterans eligible to enroll for Veterans Affairs health care. Knowledge of these differences is important in planning better services for Veterans who enroll and in encouraging additional enrollment. METHODS: We compared characteristics of enrollees and eligible Veterans in 2012. To describe enrollees, we used aggregate data from administrative records and results from VHA's Survey of Veteran Enrollees' Health and Reliance Upon VA. To describe eligible Veterans, we analyzed individual-level data from the Behavioral Risk Factor Surveillance System. RESULTS: Elderly individuals are more heavily represented among enrollees than eligible Veterans, and elderly enrollees are less likely to describe their health as good to excellent. Enrollees are more than twice as likely as eligible Veterans to have annual household incomes below $16,000. Representation of minorities is roughly the same among enrollees as eligible Veterans. CONCLUSIONS: Our results are consistent with VHA as a safety net provider with respect to income, age, and disease burden.
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Atención a la Salud/organización & administración , Gastos en Salud , Medicina Militar/métodos , Encuestas y Cuestionarios , United States Department of Veterans Affairs , Veteranos/estadística & datos numéricos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Renta , Masculino , Persona de Mediana Edad , Factores Socioeconómicos , Estados UnidosRESUMEN
Primary care providers are increasingly important in the treatment of patients with the hepatitis C virus, especially for the large cohort of veterans born between 1945 and 1965.