Clinical care pathways for patients with hepatitis C: reducing critical barriers to effective treatment.

Background: Engagement of individuals infected with hepatitis C virus (HCV) with care pathways remains a major barrier to realizing the benefits of new and more effective antiviral therapies. After an exploratory study, we have undertaken an evidence-basedredesign of care pathways for HCV, including the following: (1) reflex testing of anti-HCV-positive samples for HCV RNA; (2) annotation of laboratory results to recommend referral of actively infected patients to specialist clinics; (3) educational programs for primary care physicians and nurses; and (4) the establishment of needs-driven community clinics in substance misuse services.Methods: In this study, we conducted a retrospective cohort study of progression through care pathways of individuals with a new diagnosis of HCV infection made between January 2010 and January 2012. We also analyzed patient flow through new care pathways and compared this with our baseline study of identical design.Results: A total of 28 980 samples were tested for anti-HCV antibody during the study period and yielded 273 unique patients with a new diagnosis of HCV infection. Of these, 38% were tested in general practice, 21% were tested in substance misuse services, 23% were tested in secondary care, and 18% were tested in local prisons. Overall, 80% of patients were referred to specialist clinics, 70% attended for assessment, and 38% commenced treatment, in comparison to 49%, 27%, and 10%, respectively, in the baseline study. Referral rates from all testing sources improved.Conclusions: This study provides timely evidence that progression through care pathways can be enhanced, and it demonstrates reduction of key barriers to eradication of HCV

Establishing the cascade of care for hepatitis C in England-benchmarking to monitor impact of direct acting antivirals

Little is known about engagement and retention in care of people diagnosed with chronic hepatitis C (HCV) in England. Establishing a cascade of care informs targeted interventions for improving case-finding, referral, treatment uptake and retention in care. Using data from the Sentinel Surveillance of Blood Borne Virus testing (SSBBV) between 2005-2014 we investigate the continuum of care of those tested for HCV in England. Persons ≥1 years old, with an anti-HCV test and subsequent RNA tests between 2005-2014 reported to SSBBV were collated. We describe the cascade of care, as the patient pathway from a diagnostic test, referral into care, treatment, and patient outcomes. Between 2005-2014, 2,390,507 samples were tested for anti-HCV, corresponding to 1,766,515 persons. 53,038 persons (35,190 men and 17,165 women) anti-HCV positive were newly reported to SSBBV. An RNA test, was conducted on 77.0% persons anti-HCV positive, 72.3% of whom were viraemic (RNA positive) during this time period, 21.4% had evidence of treatment, and 3130 49.5% had evidence of a sustained virological response (SVR). In multivariable models confirmation of viraemia by RNA test varied by age and region/test setting; evidence of treatment varied by age, year of test and region/test setting; and SVR varied by age, year of test and region/setting of test. In conclusion, Our findings provide HCV cascade of care estimates prior to the introduction of direct acting antivirals. These findings provide important baseline cascade estimates to benchmark progress towards elimination of HCV as a major public health threat

Establishing the cascade of care for hepatitis C in England-benchmarking to monitor impact of direct acting antivirals

Little is known about engagement and retention in care of people diagnosed with chronic hepatitis C (HCV) in England. Establishing a cascade of care informs targeted interventions for improving case-finding, referral, treatment uptake and retention in care. Using data from the Sentinel Surveillance of Blood Borne Virus testing (SSBBV) between 2005-2014 we investigate the continuum of care of those tested for HCV in England.Persons ≥1 years old, with an anti-HCV test and subsequent RNA tests between 2005-2014 reported to SSBBV were collated. We describe the cascade of care, as the patient pathway from a diagnostic test, referral into care, treatment, and patient outcomes.Between 2005-2014, 2,390,507 samples were tested for anti-HCV, corresponding to 1,766,515 persons. 53,038 persons (35,190 men and 17,165 women) anti-HCV positive were newly reported to SSBBV. An RNA test, was conducted on 77.0% persons anti-HCV positive, 72.3% of whom were viraemic (RNA positive) during this time period, 21.4% had evidence of treatment, and 3130 49.5% had evidence of a sustained virological response (SVR). In multivariable models confirmation of viraemia by RNA test varied by age and region/test setting; evidence of treatment varied by age, year of test and region/test setting; and SVR varied by age, year of test and region/setting of test. In conclusion,Our findings provide HCV cascade of care estimates prior to the introduction of direct acting antivirals. These findings provide important baseline cascade estimates to benchmark progress towards elimination of HCV as a major public health threat

Molecular Analysis of Precursor Lesions in Familial Pancreatic Cancer

PMCID: PMC3553106This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Using surveillance data to determine treatment rates and outcomes for patients with chronic hepatitis C virus infection

The aim of this work was to develop and validate an algorithm to monitor rates of, and response to, treatment of patients infected with hepatitis C virus (HCV) across England using routine laboratory HCV RNA testing data. HCV testing activity between January 2002 and December 2011 was extracted from the local laboratory information systems of a sentinel network of 23 laboratories across England. An algorithm based on frequency of HCV RNA testing within a defined time period was designed to identify treated patients. Validation of the algorithm was undertaken for one center by comparison with treatment data recorded in a clinical database managed by the Trent HCV Study Group. In total, 267,887 HCV RNA test results from 100,640 individuals were extracted. Of these, 78.9% (79,360) tested positive for viral RNA, indicating an active infection, 20.8% (16,538) of whom had a repeat pattern of HCV RNA testing suggestive of treatment monitoring. Annual numbers of individuals treated increased rapidly from 468 in 2002 to 3,295 in 2009, but decreased to 3,110 in 2010. Approximately two thirds (63.3%; 10,468) of those treated had results consistent with a sustained virological response, including 55.3% and 67.1% of those with a genotype 1 and non-1 virus, respectively. Validation against the Trent clinical database demonstrated that the algorithm was 95% sensitive and 93% specific in detecting treatment and 100% sensitive and 93% specific for detecting treatment outcome. Conclusions: Laboratory testing activity, collected through a sentinel surveillance program, has enabled the first country-wide analysis of treatment and response among HCV-infected individuals. Our approach provides a sensitive, robust, and sustainable method for monitoring service provision across Englan

The Impact of HCV Infection Duration on HIV Disease Progression and Response to cART amongst HIV Seroconverters in the UK

The effect of HCV infection on HIV disease progression remains unclear; the effect of HCV infection duration on HIV disease progression is unknown

Establishing the cascade of care for hepatitis C in England-benchmarking to monitor impact of direct acting antivirals

Little is known about engagement and retention in care of people diagnosed with chronic hepatitis C (HCV) in England. Establishing a cascade of care informs targeted interventions for improving case-finding, referral, treatment uptake and retention in care. Using data from the Sentinel Surveillance of Blood Borne Virus testing (SSBBV) between 2005-2014 we investigate the continuum of care of those tested for HCV in England. Persons ≥1 years old, with an anti-HCV test and subsequent RNA tests between 2005-2014 reported to SSBBV were collated. We describe the cascade of care, as the patient pathway from a diagnostic test, referral into care, treatment, and patient outcomes. Between 2005-2014, 2,390,507 samples were tested for anti-HCV, corresponding to 1,766,515 persons. 53,038 persons (35,190 men and 17,165 women) anti-HCV positive were newly reported to SSBBV. An RNA test, was conducted on 77.0% persons anti-HCV positive, 72.3% of whom were viraemic (RNA positive) during this time period, 21.4% had evidence of treatment, and 3130 49.5% had evidence of a sustained virological response (SVR). In multivariable models confirmation of viraemia by RNA test varied by age and region/test setting; evidence of treatment varied by age, year of test and region/test setting; and SVR varied by age, year of test and region/setting of test. In conclusion, Our findings provide HCV cascade of care estimates prior to the introduction of direct acting antivirals. These findings provide important baseline cascade estimates to benchmark progress towards elimination of HCV as a major public health threat

Data from: The impact of HCV infection duration on HIV disease progression and response to cART amongst HIV seroconverters in the UK

Introduction: The effect of HCV infection on HIV disease progression remains unclear; the effect of HCV infection duration on HIV disease progression is unknown. Methods: We used data from a cohort of HIV seroconverters to investigate the effect of HCV infection duration on time from HIV seroconversion to CD4 4 years). We additionally compared CD4 cell decline following HCV infection to that of mono-infected individuals with similar HIV infection duration by fitting a random effects model. In a separate analysis, we used linear mixed models to we examine the effect of HCV infection and its duration on CD4 increase over 48 weeks following cART. Results: Of 1655 individuals, 97 (5.9%) were HCV co-infected. HCV4 years respectively), compared to mono-infected individuals. However, we found no evidence of an association for those with HCV>2 years (all p>0.89). Individuals experienced a somewhat greater decrease in CD4 count following HCV infection lasting 13 months, relative to individuals with HIV alone, (estimate = -3.33, 95% CI [-7.29, 0.63] cells/mm3 per month, p = 0.099). Of 1502 initiating cART, 106 (7.1%) were HCV co-infected, with no evidence of HCV duration at cART being associated with immunological response (p = 0.45). Conclusions: The impact of HCV co-infection on HIV disease progression appears to be restricted to the first year after HCV infection

cd4_data_primary_dryad

Dataset containing all CD4 data from those individuals included in the primary analysis investigating time from HIV seroconversion to HIV disease progression

HIV type-1 drug resistance in antiretroviral treatment-naive adults infected with non-B subtype virus in the United Kingdom.

BACKGROUND: There is an increasing prevalence of non-B subtype HIV type-1 (HIV-1) infections in Europe, reflecting patterns of migration. We examined the characteristics of HIV-1 drug resistance in antiretroviral treatment (ART)-naive individuals migrating to the UK. METHODS: Resistance tests reported to the UK HIV Drug Resistance Database between 2001 and 2006 were included. Demographic data were obtained via linkage to national databases. Resistance was defined as ≥ 1 drug resistance mutation. Non-B HIV-1 subtype was used as a surrogate marker of infection acquired outside the UK. Logistic regression was used to examine the association between demographics and the prevalence of resistance. RESULTS: Overall, 196/4,291 (4.6%) samples with non-B subtype showed resistance compared with 745/6,435 (11.6%) samples for subtype B. Among non-B subtypes, the prevalence of resistance decreased over time (6.0% in 2001-2003 to 3.2% in 2006) and was independently associated with later calendar year of sampling (P=0.001). Resistance was confined mainly to one ART class (85%); non-nucleoside reverse transcriptase inhibitor resistance was more common in subtype C (47%) compared with non-B non-C subtypes (29%; P=0.02). M184V was more common in non-B subtypes (non-B 30% versus B 5%; P<0.001) and T215 variants were more common in subtype B (non-B 10% versus B 49%; P<0.001). CONCLUSIONS: In ART-naive individuals living in the UK, but who are likely to have acquired HIV-1 abroad, we observed a downward trend in resistance over time, which is surprising in light of ART roll-out in resource-limited settings. Reassuringly, resistance was mainly confined to one drug class; however, patterns of resistance differed by subtype, with some evidence of possible undisclosed prior therapy in non-B subtypes