Hepatitis C Virus RNA Testing Research Articles

Understanding hepatitis C virus (HCV) health literacy and educational needs among people in prison to enhance HCV care in prisons

BackgroundHepatitis C virus (HCV) is a significant concern within prison populations. Provision of HCV testing and treatment for people in prison is expanding and a key component of global elimination efforts. Despite growing service availability, several challenges remain in HCV testing and treatment engagement during incarceration. The PIVOT study demonstrated that a ‘one-stop-shop’ intervention (point-of-care HCV RNA testing, Fibroscan®, nurse-led clinical assessment, and fast-tracked direct-acting antiviral prescription) enhanced HCV testing and treatment at a reception prison in Australia. Utilising Squier et al's Health Literacy Skills Framework, this analysis aimed to understand HCV health literacy and educational needs among people at a reception prison in Australia. MethodsSemi-structured interviews were conducted with twenty-four male PIVOT study participants. Purposive sampling ensured comparable representation of those with: 1) prior HCV testing history (standard pathology / no prior testing), and 2) injecting drug use history (IDU; ever / never). ResultsVaried HCV health literacy levels and educational needs were evident amongst people in prison. Whilst those with multiple incarceration episodes and IDU history (prior knowledge) appeared to have stronger HCV health literacy than those without, substantial gaps in HCV health literacy were evident. Knowledge of HCV transmission risks in prison was high, and most understood the importance of HCV testing and treatment in prison (comprehension), but ability to engage with HCV testing and treatment services, participation in safe injecting behaviours (health-related behaviours), and knowledge of re-infection and re-treatment, within the context of the prison environment, were suboptimal. There was a general desire for increased HCV education in prison. ConclusionGaps in HCV health literacy among people in prison were evident, indicating opportunities for improvement. A targeted HCV education program for people in prison, addressing the gaps identified in this analysis, may enhance HCV testing, treatment, and prevention by fostering stronger HCV health literacy among people in prison.

HCV prevalence and phylogenetic characteristics in a cross-sectional, community study of young people who inject drugs in New York City: Opportunity for and threats to HCV elimination.

In the United States, the opioid epidemic has led many young people who use opioids to initiate injection drug use, putting them at risk for hepatitis C virus (HCV) infection. However, community surveys to monitor HCV prevalence among young people who inject drugs (YPWID) are rare. As part of Staying Safe (Ssafe), a trial to evaluate an HCV-prevention intervention, a community-recruited sample of 439 young people who use opioids (ages 18-30) in New York City (NYC) were screened from 2018 to 2021. Screening procedures included a brief verbal questionnaire, a visual check for injection marks, onsite urine drug testing, rapid HCV antibody (Ab) testing, and dried blood spot (DBS) collection. DBS specimens were sent to a laboratory for HCV RNA testing and phylogenetic analysis to identify genetic linkages among HCV RNA-positive specimens. Multivariable logistic regression was used to assess associations between HCV status (Ab and RNA) and demographics and drug use patterns. Among the 330 participants who reported injecting drugs (past 6 months), 33% (n = 110) tested HCV Ab-positive, 58% of whom (n = 64) had HCV RNA-positive DBS specimens, indicating active infection. In multivariable analysis, visible injection marks (AOR = 3.02; p < 0.001), older age (AOR = 1.38; p < 0.05), and female gender (AOR = 1.69; p = 0.052) were associated with HCV Ab-positive status. Visible injection marks were also associated with HCV RNA-positive status (AOR = 5.24; p < 0.01). Twenty-five percent of RNA-positive specimens (14/57) were genetically linked. The relatively low prevalence of active infection suggests the potential impact of treatment-as-prevention in reducing HCV prevalence among YPWID. Targeted community serosurveys could help identify actively infected YPWID for treatment, thereby reducing HCV incidence and future transmissions.

#1050 Diabetes mellitus mediates the association between chronic hepatitis C virus infection and incidence of end-stage kidney disease

Abstract Background and Aims Chronic infection with the hepatitis C virus (HCV) is known to lead to extra-hepatic complications, notably affecting the kidneys. While prior research has established a link between chronic HCV infection and chronic kidney disease (CKD), there remains ongoing debate regarding whether this association is influenced by the presence of diabetes mellitus. Method This study, part of the REVEAL-HCV project in Taiwan, investigated the relationship between chronic HCV infection and end-stage kidney disease (ESKD). Initially, 23,820 individuals aged 30-65 from Taiwan were enrolled since 1991-1992. Data included physical exams, blood tests, and questionnaires covering sociodemographics, lifestyle, and comorbidities. The cohort was linked to Taiwan's National Health Insurance Research Database, providing extensive patient data. Hepatitis C status was determined by HCV RNA testing. ESKD was identified using ICD-9-CM codes from the health database. Covariates like age, sex, lifestyle factors, comorbidities, and lab results were considered. The study emphasized accurate diagnosis of diabetes based on insurance claims with well validation. The mediation analysis was done by constructing 2 logistic regression models, with one regressing the risk of ESKD on chronic HCV infection status and the other regressing the risk of ESKD on diabetes status. The direct and indirect (mediated through the risk of diabetes) effects of chronic HCV infection on the risk of ESKD were estimated using odds ratios. Confidence intervals for direct and indirect effects were estimated using 5000 bootstrapping replicates. Results The study examined 22,800 participants, with a mean age of 46.9 years. Among them, 738 were chronically infected with HCV. These HCV-infected participants were generally older, more likely to be female, had lower education levels, and higher prevalence of diabetes, hypertension, and CKD. During the 16.8-year median follow-up, covering 319,474 person-years, 378 end-stage kidney disease (ESKD) events occurred. The incidence of ESKD was higher in HCV-infected subjects (2.6%) compared to non-HCV-infected (1.6%). The univariate and multivariate-adjusted odds ratios (ORs) and 95% confidence interval for ESKD in HCV-infected participants were 2.06 (0.90-2.08) and 1.57 (1.01-2.44), respectively. HCV infection also showed a significant association with diabetes mellitus. The multivariable-adjusted OR for diabetes in HCV-infected individuals was 1.53 (1.31-1.78). Further, the study identified a diabetes-mediated pathway linking HCV infection to ESKD. In this pathway, HCV infection increased the odds of ESKD by 0.8%. This indirect pathway mediated by diabetes accounted for 16% of the overall association between HCV infection and ESKD with statistically significant. The direct pathway, though not statistically significant, indicated a 57% increased odds of ESKD in HCV-infected individuals compared to those without HCV. Conclusion Chronic HCV infection is linked to higher incidences of diabetes and ESKD. The mechanisms are intricate, with diabetes serving as a significant mediator in the pathway from HCV infection to ESKD.

Successes and challenges of best practice alerts to identify and engage individuals living with hepatitis C virus.

Many individuals living with hepatitis C virus (HCV) are unaware of their diagnosis and/or have not been linked to programs providing HCV care. The use of electronic medical record (EMR) systems may assist with HCV infection identification and linkage to care. In October 2021, we implemented HCV serology-focused best practice alerts (BPAs) at The Ottawa Hospital (TOH) via our EMR (EPIC). Our BPAs were programmed to identify previously tested HCV seropositive individuals. Physicians were prompted to conduct HCV RNA testing and submit consultation requests to the TOH Viral Hepatitis Program. We evaluated data post-BPA implementation to assess the design and related outcomes. From 1 September 2022 to 15 December 2022, a total of 2,029 BPAs were triggered for 139 individuals. As a consequence of the BPA prompts, nine HCV seropositive and nine HCV RNA-positive individuals were linked to care. The proportion of total consultations coming from TOH physicians increased post-BPA implementation. The BPA alerts were frequently declined, and physician engagement with our BPAs varied across specialty groups. Programming issues led to unnecessary BPA prompts (e.g., no hard stop to the prompts even though the individual was treated and cured and individuals linked to care without first undergoing HCV RNA testing). A fixed 6-month lookback period for test results limited our ability to identify many individuals. An EMR-based BPA can assist with the identification and engagement of HCV-infected individuals in care. However, challenges including issues with programming, time commitment toward BPA configuration, productive communication between healthcare providers and the programming team, and physician responsiveness to the BPAs require attention to optimize the impact of BPAs.

Four weeks of off-treatment follow-up is sufficient to determine virologic responses at off-treatment week 12 in patients with hepatitis C virus infection receiving fixed-dose pangenotypic direct-acting antivirals.

Early confirmation of sustained virologic response (SVR) or viral relapse after direct-acting antivirals (DAAs) for hepatitis C virus (HCV) infection is essential based on public health perspectives, particularly for patients with high risk of nonadherence to posttreatment follow-ups. A total of 1011 patients who achieved end-of-treatment virologic response, including 526 receiving fixed-dose pangenotypic DAAs, and 485 receiving other types of DAAs, who had available off-treatment weeks 4 and 12 serum HCV RNA data to confirm SVR at off-treatment week 12 (SVR12) or viral relapse were included. The positive predictive value (PPV) and negative predictive value (NPV) of SVR4 to predict patients with SVR12 or viral relapse were reported. Furthermore, we analyzed the proportion of concordance between SVR12 and SVR24 in 943 patients with available SVR24 data. The PPV and NPV of SVR4 to predict SVR12 were 98.5% (95% confidence interval [CI]: 98.0-98.9) and 100% (95% CI: 66.4-100) in the entire population. The PPV of SVR4 to predict SVR12 in patients receiving fixed-dose pangenotypic DAAs was higher than those receiving other types of DAAs (99.8% [95% CI: 98.9-100] vs. 97.1% [95% CI: 96.2-97.8], p < 0.001). The NPVs of SVR4 to predict viral relapse were 100%, regardless of the type of DAAs. Moreover, the concordance between SVR12 and SVR24 was 100%. In conclusion, an off-treatment week 4 serum HCV RNA testing is sufficient to provide an excellent prediction power of SVR or viral relapse at off-treatment week 12 among patients with HCV who are treated with fixed-dose pangenotypic DAAs.

Factors associated with hepatitis C testing, treatment, and current hepatitis C infection among men and women who inject drugs: The ETHOS engage study

BackgroundEvaluating gender-specific trends in hepatitis C virus (HCV) treatment uptake among men and women who inject drugs is crucial for ensuring equitable progress towards HCV elimination. This study aimed to quantify differences in testing, treatment, and current HCV infection between men and women who inject drugs. MethodETHOS Engage is an observational cohort study of people who inject drugs attending drug treatment clinics and needle and syringe programs in Australia recruited from May 2018-September 2019 (wave 1) and November 2019-April 2021 (wave 2). Participants completed a questionnaire including self-reported HCV testing and treatment history and underwent point-of-care HCV RNA testing (Xpert® HCV Viral Load Fingerstick). Logistic regression was used to compare the factors associated with self-reported HCV testing and treatment and current HCV infection for men and women who inject drugs. ResultsAmong 2,395 participants enrolled in ETHOS Engage, 66% (n = 1,591) were men, 33% (n = 786) women, and <1% (n = 18) did not identify as a man or woman. HCV testing history and current infection were similar among men and women. Among men or women ever eligible for HCV treatment (ever chronic HCV) (n = 1,242), women were less likely to report a history of HCV treatment compared to men (227/352, 64% vs. 631/890, 71%; p = 0.03). Among women, those aged <45 were less likely to report HCV testing (aOR: 0.57, 95%CI: 0.36, 0.90), treatment (aOR: 0.47, 95%CI: 0.29, 0.77), and more likely to have HCV infection (aOR: 1.48, 95%CI: 1.00, 2.20) ConclusionAmong women, those of childbearing age (<45) were less likely to report testing and treatment and were more likely to have current HCV infection. Women <45 years old should be a priority population for HCV care. Services that interface with these women should be optimised to enhance HCV testing and treatment.

The Epidemiology of Chronic Hepatitis C: Where We Are Now

One of the main objectives of the World Health Organization is the eradication of viral hepatitis by 2030 by identifying subjects before disease progression. In 2019, only 21% of the 58 million people chronically infected with hepatitis C virus (HCV) had been diagnosed, while overall 13% had been treated. The key recommendation of international screening programs is to reach the people at major risk of viral hepatitis and the general population. National plans, including that in Italy, have dedicated budget lines to support efforts to achieve the objective of elimination. The Italian program involves free screening for HCV in the general population born between 1969 and 1989 and also for all persons in the care of addiction services (Ser.D) and prisoners. The screening programs differed slightly among regions in Italy. In particular, referring to the screening for people born in the period of 1969–1989, in Tuscany, these people received an invitation by SMS to undergo a HCV antibody test. If the test results were positive, the subject was registered on a regional platform and required to undergo HCV RNA testing, prescribed by their GP. In the case of testing positive for HCV RNA, the linkage to care (i.e., patient entry into specialist care after diagnosis) is guaranteed. A strong effort is currently required to eliminate HCV effectively. This review highlights the most recent changes to the epidemiological scenario at the global, European, Italian, and regional (Tuscany) levels.

Hepatitis C virus infection and co-infection with HIV among persons who inject drugs in 10 U.S. cities—National HIV Behavioral Surveillance, 2018

BackgroundCharacterizing acute and chronic hepatitis C virus (HCV) infection and HIV/HCV co-infection among persons who inject drugs (PWID) can inform elimination efforts. MethodsDuring 2018 National HIV Behavioral Surveillance in 10 U.S. metropolitan statistical areas (MSAs), PWID were recruited using respondent-driven sampling and offered a survey, HIV testing, and HCV antibody and RNA testing. We examined prevalence and associated characteristics of HCV infection and HIV/HCV co-infection. Associations were assessed using log-linked Poisson regression models with robust standard errors accounting for clustering by recruitment chain and adjusting for MSA and network size. ResultsOverall, 44.2% had current HCV infection (RNA detected), with 3.9% classified as acute infection (HCV antibody non-reactive/RNA detected) and 40.3% as chronic (HCV antibody reactive/RNA detected). Four percent had HIV/HCV co-infection. Current HCV infection was significantly higher among PWID who were male, White, injected >1 time/day, shared syringes in past year, and shared injection equipment in past year. PWID who were transgender, injecting >5 years, and most often injected speedball (heroin and cocaine together) or stimulants alone were more likely to have HIV/HCV co-infection. Among PWID who never previously had HCV infection, 9.9% had acute HCV infection. Among PWID who started injecting ≤5 years ago, 41.5% had already acquired HCV infection. ConclusionsAcute and chronic HCV infections were substantial among a sample of PWID in 10 U.S. MSAs. Accessibility to HCV RNA testing, promoting safer practices, and intervening early with harm reduction programs for recent injection initiates will be critical to disease elimination efforts for PWID.

Integration of Hepatitis C and Addiction Treatment in People Who Inject Drugs: The San Patrignano HCV-Free and Drug-Free Experience.

Injection drug use represents an important contributor to hepatitis C virus (HCV) transmission, hence therapeutic communities (TCs) are promising points of care for the identification and treatment of HCV-infected persons who inject drugs (PWIDs). We evaluated the effectiveness and efficacy of an HCV micro-elimination program targeting PWIDs in the context of a drug-free TC; we applied the cascade of care (CoC) evaluation by calculating frequencies of infection diagnosis, confirmation, treatment and achievement of a sustained virological response (SVR). We also evaluated the risk of reinfection of PWIDs achieving HCV eradication by collecting follow-up virologic information of previously recovered individuals and eventual relapse in drug use, assuming the latter as a potential source of reinfection. We considered 811 PWIDs (aged 18+ years) residing in San Patrignano TC at the beginning of the observation period (January 2018-March 2022) or admitted thereafter, assessing for HCV and HIV serology and viral load by standard laboratory procedures. Ongoing infections were treated with direct-acting antivirals (DAA), according to the current national guidelines. Out of the 792 individuals tested on admission, 503 (63.5%) were found to be seropositive for antibodies against HCV. A total of 481 of these 503 individuals (95.6%) underwent HCV RNA testing. Out of the 331 participants positive for HCV RNA, 225 were ultimately prescribed a DAA treatment with a sustained viral response (SVR), which was achieved by 222 PWIDs (98.7%). Of the 222 PWIDs, 186 (83.8%) with SVR remained HCV-free on follow-up (with a median follow-up of 2.73 years after SVR ascertainment). The CoC model in our TC proved efficient in implementing HCV micro-elimination, as well as in preventing reinfection and promoting retention in the care of individuals, which aligns with the therapeutic goals of addiction treatment.

Improving the hepatitis C virus care cascade with the in-hospital Reflex tEsting ALarm-C (REAL-C) model.

The World Health Organization (WHO) has set targets to eliminate viral hepatitis, including hepatitis C virus (HCV) infection, by 2030. We present the results of the in-hospital Reflex tEsting ALarm-C (REAL-C) model, which incorporates reflex HCV RNA testing and sending alerts to physicians. We conducted a retrospective study analysing the data of 1730 patients who newly tested positive for anti-HCV between March 2020 and June 2023. Three distinct periods were defined: pre-REAL-C (n = 696), incomplete REAL-C (n = 515) and complete REAL-C model periods (n = 519). The primary outcome measure was the HCV RNA testing rate throughout the study period. Additionally, we assessed the referral rate to the gastroenterology department, linkage time for diagnosis and treatment and the treatment rate. The rate of HCV RNA testing increased significantly from 51.0% (pre-REAL-C) to 95.6% (complete REAL-C). This improvement was consistent across clinical departments, regardless of patients' comorbidities. Among patients with confirmed HCV infection, the gastroenterology referral rate increased from 57.1% to 81.1% after the REAL-C model. The treatment rate among treatment-eligible patients was 92.4% during the study period. The mean interval from anti-HCV positivity to HCV RNA testing decreased from 45.1 to 1.9 days. The mean interval from the detection of anti-HCV positivity to direct-acting antiviral treatment also decreased from 89.5 to 49.5 days with the REAL-C model. The REAL-C model, featuring reflex testing and physician alerts, effectively increased HCV RNA testing rates and streamlined care cascades. Our model facilitated progress towards achieving WHO's elimination goals for HCV infection.

Risk of Primary Incident Hepatitis C Infection Following Bacterial Sexually Transmissible Infections Among Gay and Bisexual Men in Australia From 2016 to 2020.

In Australia, the incidence of hepatitis C virus (HCV) has declined among gay and bisexual men (GBM) with human immunodeficiency virus (HIV) since 2015 and is low among GBM using HIV preexposure prophylaxis (PrEP). However, ongoing HCV testing and treatment remains necessary to sustain this. To assess the potential utility of sexually transmissible infections (STIs) to inform HCV testing among GBM with HIV and GBM using PrEP, we examined the association between bacterial STI diagnoses and subsequent primary HCV infection. Data were from a national network of 46 clinics participating in the Australian Collaboration for Coordinated Enhanced Sentinel Surveillance. GBM included had ≥1 HCV antibody negative test result and ≥1 subsequent HCV antibody and/or RNA test. Discrete time survival analysis was used to estimate the association between a positive syphilis, rectal chlamydia, and rectal gonorrhea diagnosis in the previous 2 years and a primary HCV diagnosis, defined as a positive HCV antibody or RNA test result. Among 6529 GBM with HIV, 92 (1.4%) had an incident HCV infection. A prior positive syphilis diagnosis was associated with an incident HCV diagnosis (adjusted hazard ratio, 1.99 [95% confidence interval, 1.11-3.58]). Among 13 061 GBM prescribed PrEP, 48 (0.4%) had an incident HCV diagnosis. Prior rectal chlamydia (adjusted hazard ratio, 2.75 [95% confidence interval, 1.42-5.32]) and rectal gonorrhea (2.54 [1.28-5.05]) diagnoses were associated with incident HCV. Diagnoses of bacterial STIs in the past 2 years was associated with HCV incidence. These findings suggest that STIs might be useful for informing HCV testing decisions and guidelines for GBM with HIV and GBM using PrEP.

Hepatitis C virus reinfection incidence among gay and bisexual men with HIV in Australia from 2016 to 2020.

There is some concern that hepatitis C virus (HCV) reinfection might impact HCV micro-elimination efforts among gay and bisexual men (GBM) with HIV. However, there is a limited understanding of reinfection incidence in the context of unrestricted government-funded HCV treatment. We aimed to estimate HCV reinfection incidence among GBM with HIV in Australia from 2016 to 2020. Data were from 39 clinics participating in ACCESS, a sentinel surveillance network for blood borne viruses and sexually transmissible infections across Australia. GBM with HIV who had evidence of treatment or spontaneous clearance with at least one positive HCV RNA test, a subsequent negative HCV RNA test, and at least one additional HCV RNA test between 1st January 2016 and 31st December 2020 were eligible for inclusion. A new HCV RNA positive test and/or detectable viral load was defined as a reinfection. Generalised linear modelling was used to examine trends in reinfection. Among 12 213 GBM with HIV who had at least one HCV test, 540 were included in the reinfection incidence analysis, of whom 38 (7%) had evidence of reinfection during the observation period. Over 1124 person-years of follow-up, the overall rate of reinfection was 3.4/100PY (95% CI 2.5-4.6). HCV reinfection incidence declined on average 30% per calendar year (Incidence Rate Ratio 0.70, 95% CI 0.54-0.91). HCV reinfection incidence has declined among GBM with HIV in Australia since government-funded unrestricted DAAs were made available. Ongoing HCV RNA testing following cure and prompt treatment for anyone newly diagnosed is warranted to sustain this.

Comparison of effectiveness and cost of different HCV testing strategies in high-risk populations in China.

High-risk populations are the predominant populations affected by hepatitis C virus(HCV) infection, and there is an urgent need for efficient and cost-effective HCV testing strategies for high-risk populations to identify potential undiagnosed HCV-infectedindividuals. This study compared several commonly used testing strategies and conducted effectiveness and cost analysis to select the appropriate testing strategy for diagnosing HCV infection in high-risk populations. Among the 2093 samples from high-risk populations in this study, 1716 were HCV negative, 237 were current HCV infection, 137 were past HCV infection, and three were acute early HCV infection. It was found that out of 237 patients with HCV current infection, Strategy A could detect 225 cases, with a missed detection rate of 5.06%, and the total cost was 33 299 RMB. In addition, Strategy B could detect 237 cases of current HCV infection, and the HCV missed detection rate was 0.00%, and the total cost was 147 221 RMB. While 137 cases of past HCV infection could be distinguished by strategy C, but 14 cases with current HCV infection were missed, with an HCV-positivemissed detection rate of 5.91%, and the total cost for Strategy C was 43 059 RMB. In conclusion, in high-risk populations, the HCV positivity rate is typically higher. If feasible, the preferred approach is to directly conduct HCV RNA testing, which effectively minimizes the risk of missing cases. However, in situations with limited resources, it is advisable to initially choose a highly sensitive method for anti-HCV screening, followed by HCV RNA testing on reactive samples.

Testing, diagnosis, and treatment following the implementation of a program to provide dried blood spot testing for HIV and hepatitis C infections: the NSW DBS Pilot

BackgroundDried blood spot (DBS) testing provides an alternative to phlebotomy and addresses barriers to accessing healthcare experienced by some key populations. Large-scale evaluations of DBS testing programs are needed to understand their feasibility. This study evaluated the implementation of a state-wide DBS HIV and hepatitis C virus (HCV) testing pilot.MethodsThe New South Wales (NSW) DBS Pilot is an interventional cohort study of people testing for HIV antibody and/or HCV RNA from DBS samples in NSW, Australia. Participants at risk of HIV/HCV participated in testing via: 1) self-registration online with a DBS collection kit delivered and returned by conventional postal service; or 2) assisted DBS sample collection at 36 community health sites (including drug treatment and harm-minimisation services) and prisons. Participants received results by text (HIV antibody/ HCV RNA not detected) or a healthcare provider (HIV antibody/ HCV RNA detected). The RE-AIM framework was used to evaluate reach, effectiveness, adoption, and implementation.ResultsReach: Between November 2016 and December 2020, 7,392 individuals were tested for HIV and/or HCV (21% self-registration, 34% assisted in community, and 45% assisted in prison). Effectiveness: Of 6,922 people tested for HIV (19% men who have sex with men, 13% living outside major cities, 21% born outside Australia), 51% (3,521/6,922) had no HIV test in the past two years, 0.1% (10/6,922) were newly diagnosed with HIV, and 80% (8/10) initiated HIV treatment within six months. Of 5,960 people tested for HCV (24% women, 35% Aboriginal and/or Torres Strait Islander, 55% recently injected drugs), 15% had detectable HCV RNA (878/5,960), and 45% (393/878) initiated treatment within six months. Adoption: By the end of 2020, DBS via assisted registration was available at 36 community sites and 21 prisons. Implementation: 90% of DBS cards arriving at the laboratory had the three full spots required for testing; the proportion was higher in assisted (94%) compared to online (76%) registration.ConclusionsThis study demonstrated the feasibility of DBS testing for HIV and HCV in key populations including Aboriginal and Torres Strait Islander peoples, men who have sex with men, people who inject drugs, and demonstrated the utility of DBS in the prison setting.

Changes in incidence of hepatitis C virus reinfection and access to direct-acting antiviral therapies in people with HIV from six countries, 2010–19: an analysis of data from a consortium of prospective cohort studies

Reinfection after successful treatment with direct-acting antivirals is hypothesised to undermine efforts to eliminate hepatitis C virus (HCV) infection among people with HIV. We aimed to assess changes in incidence of HCV reinfection among people with HIV following the introduction of direct-acting antivirals, and the proportion of all incident cases attributable to reinfection. We pooled individual-level data on HCV reinfection in people with HIV after spontaneous or treatment-induced clearance of HCV from six cohorts contributing data to the International Collaboration on Hepatitis C Elimination in HIV Cohorts (InCHEHC) in Australia, Canada, France, the Netherlands, Spain, and Switzerland between Jan 1, 2010, and Dec 31, 2019. Participants were eligible if they had evidence of an HCV infection (HCV antibody or RNA positive test) followed by spontaneous clearance or treatment-induced clearance, with at least one HCV RNA test after clearance enabling measurement of reinfection. We assessed differences in first reinfection incidence between direct-acting antiviral access periods (pre-direct-acting antiviral, limited access [access restricted to people with moderate or severe liver disease and other priority groups], and broad access [access for all patients with chronic HCV]) using Poisson regression. We estimated changes in combined HCV incidence (primary and reinfection) and the relative contribution of infection type by calendar year. Overall, 6144 people with HIV who were at risk of HCV reinfection (median age 49 years [IQR 42-54]; 4989 [81%] male; 2836 [46%] men who have sex with men; 2360 [38%] people who inject drugs) were followed up for 17 303 person-years and were included in this analysis. The incidence of first HCV reinfection was stable during the period before the introduction of direct-acting antivirals (pre-introduction period; 4·1 cases per 100 person-years, 95% CI 2·8-6·0). Compared with the pre-introduction period, the average incidence of reinfection was 4% lower during the period of limited access (incidence rate ratio [IRR] 0·96, 95% CI 0·78-1·19), and 28% lower during the period of broad access (0·72, 0·60-0·86). Between 2015 and 2019, the proportion of incident HCV infections due to reinfection increased, but combined incidence declined by 34%, from 1·02 cases per 100 person-years (95% CI 0·96-1·07) in 2015 to 0·67 cases per 100 person-years (95% CI 0·59-0·75) in 2019. HCV reinfection incidence and combined incidence declined in people with HIV following direct-acting antiviral introduction, suggesting reinfection has not affected elimination efforts among people with HIV in InCHEHC countries. The proportion of incident HCV cases due to reinfection was highest during periods of broad access to direct-acting antivirals, highlighting the importance of reducing ongoing risks and continuing testing in people at risk. Australian National Health and Medical Research Council.

A Composite Score for Predicting Vertical Transmission of Hepatitis C: A Multicenter Study.

Prevention of the vertical transmission of the hepatitis C virus (HCV) presents an obstetric challenge. There are no approved antiviral medications for the treatment or prevention of HCV for pregnant patients. We aimed to create a composite score to accurately identify a population of pregnant patients with HCV who have high potential for vertical transmission. In a retrospective, multicenter cohort study, we identified pregnant patients with hepatitis C with linked data to their infants who have had HCV RNA or HCV antibody testing. Demographic data, including age and race/ethnicity, as well as clinical and laboratory data, including tobacco/alcohol use, infections, liver function tests, the HCV RNA titer, HCV antibody, HCV genotype, absolute lymphocyte count, and platelet count, were collected. Data were analyzed using logistic regression and receiver operating characteristics (ROCs) and internally validated using the forward selection bootstrap method. We identified 157 pregnant patients and 163 corresponding infants. The median maternal delivery age was 29 (IQR: 25-33) years, and the majority (141, or 89.8%) were White. A high HCV RNA titer, high absolute lymphocyte count, and high platelet count were associated with vertical transmission. A high HCV RNA titer had an AUROC of 0.815 with sensitivity, specificity, a positive predictive value, and a negative predictive value of 100.0%, 59.1%, 17.6%, and 100.0%, respectively. A composite score combining the three risk factors had an AUROC of 0.902 (95% CI = 0.840-0.964) but with a risk of overfitting. An HCV RNA titer alone or a composite score combining the risk factors for HCV vertical transmission can potentially identify a population of pregnant patients where the rate of vertical transmission is high, allowing for potential interventions during antepartum care.

Performance Evaluation of the Roche Cobas 5800 HBV and HCV Tests: Comparison of the 200 and 500 μL Protocols.

Clinical management of patients infected with hepatitis B virus (HBV) or hepatitis C virus (HCV) relies on the viral load (VL). The Cobas 5800 system (Roche Diagnostics) can determine VLs in 200 and 500 μL samples, but the performance of each protocol has not been compared. We evaluated the performance of both protocols for the HBV and HCV tests. Precision and linearity were verified using commercial panels. Probit analyses were used to determine limits of detection (LoDs). The results obtained with 336 samples were compared using the 200 and 500 μL protocols. Data from 6,737 retrospective HBV and 768 HCV samples were compared to estimate the effects of the different LoDs on the diagnostic results of the protocols. Correlations between protocols were tested with Spearman's rank correlation coefficients (rho). The precision and linearity of both protocols were verified. The LoDs for the 200 and 500 μL protocols were 6.5 and 2.7 IU/mL for HBV and 29.7 and 8.2 IU/mL for HCV, respectively. The agreement between the protocols ranged from 0.8 to 1.0. The results obtained with the HBV and HCV tests showed a strong correlation (rho=0.994). Only 0.4% of HBV and 0.4% of HCV test results were affected by the LoDs of the 200 μL protocol. The Cobas 5800 200 and 500 μL protocols for the HBV DNA and HCV RNA tests demonstrated excellent performance. These findings establish the 200 μL protocol as a new option for low-volume samples, especially for pediatric and difficult-to-bleed patients.

2502. Best Practice Alert for Hepatitis C Virus Screening Demonstrates Importance of Reminders during Disruptive Times (COVID-19)

Abstract Background In 2015, a Best Practice Alert (BPA) was implemented into our electronic health record that prompts ordering of Hepatitis C Virus (HCV) antibody (Ab) screens for unscreened patients born between 1945-1965 (baby boomers: BB). The BPA begins the first step of the three-step care cascade, after which follow-up is needed for RNA testing if Ab-positive and HCV clinic visit if RNA-positive (figure 1). Prior studies found a 3.5-fold increase in HCV Ab screening after BPA implementation. We sought to understand the BPA’s role in cascade navigation during the COVID-19 pandemic. Initial BPA is triggered, which leads to subsequent steps including HCV antibody testing, HCV RNA testing, and ending with a clinic visit for treatment initiation. Methods This retrospective study included BB receiving their first BPA between 7/1/18-12/31/19 (pre-pandemic: PP) and 1/1/20-7/1/21, (intra-pandemic: IP), excluding patients with a death date ≤ 180 days after their BPA. Patients were followed for 180 days for each step and were marked unsuccessful if it was not completed. Successful navigation (SN) was defined as completing all steps or testing negative at any step. Hazard ratios for completion of each step were calculated via Cox Proportional Model. Clinical and demographic predictors of SN were examined via multivariable logistic regression in each cohort. Results Overall, 14,236 unscreened BB had a BPA (8,090 PP, 6,146 IP) fire during the study periods. The cohorts were similar, except for an increase in share with county financial assistance and those cared for by advanced practice providers in the IP cohort (table 1). An increase in HCV Ab screening (aHR 1.31 [95% CI: 1.25, 1.38]) and decreases in HCV RNA testing (aHR 0.79 [0.65, 0.96]) and clinic visits (aHR 0.43 [0.28, 0.66]) were seen in the IP cohort (figures 2A, B, and C). Hispanic patients had increased odds (aOR: 1.25 [1.02, 1.54]) of SN in the IP cohort (figures 3A and B). Compared to family medicine, those cared for in geriatric clinics had lower odds (aOR 0.75 [0.62, 0.91]) of SN in the IP cohort. Lower odds were also seen for those with Charlson Index ≥ 2 (aOR 0.85 [0.74, 0.98]) compared to 0.Table 1.Cohort Demographics.Baseline demographic, comorbidity, and provider factors for the pre-pandemic and intra-pandemic cohorts. Figure 2. Survival-Time Analysis of the HCV Care Cascade. Kaplan-Meier curves with 95% confidence intervals depicting time to completion by day after step initiation in each cohort. Data for the HCV antibody screening (A), HCV RNA testing (B), and liver clinic visit (C) steps are each shown separately. Log-rank test p-values are shown. Figure 3. Logistic Regression Forest Plots Forest plots showing the adjusted odds ratios and 95% confidence intervals for successful cascade navigation in the pre-pandemic (A) and intra-pandemic (B) cohorts. Odds ratio less than 1 indicates lower odds of successful navigation during that period. Odds ratio greater than 1 indicates higher odds of successful navigation. Conclusion The BPA increased the durability of HCV Ab screening rates during the pandemic compared to other steps in the cascade. Disparities in completing all steps of the cascade persisted and likely worsened in some groups during the pandemic. Overall, electronic reminders lessen impacts of disruptions in healthcare services. Disclosures Mamta K. Jain, MD, MPH, Gilead Sciences: Grant/Research Support|Laurent: Grant/Research Support

Global, regional, and country-level coverage of testing and treatment for HIV and hepatitis C infection among people who inject drugs: a systematic review

People who inject drugs are disproportionately affected by HIV and hepatitis C virus (HCV) infections, while there is little global data on HIV and HCV testing and treatment coverage of this population. We conducted a systematic review to evaluate country-level, regional, and global coverage of HIV and HCV testing and treatment among people who inject drugs. We did a systematic review, and searched bibliographic databases (MEDLINE, Embase, and PsycINFO) and grey literature for studies published between Jan 1, 2017, and April 30, 2022, that evaluated the proportion of people who inject drugs who received testing or treatment for HIV or HCV. For each country, we estimated the proportion of people who inject drugs tested for HIV antibodies in the past 12 months (recent), people who inject drugs ever tested for HCV antibodies and HCV RNA, people who inject drugs with HIV currently receiving antiretroviral therapy, and people who inject drugs with HCV ever receiving HCV antiviral treatment. Regional and global estimates, weighted by the population size of people who inject drugs, were generated where sufficient data were available. This study is registered with PROSPERO (CRD42020173974). 512 documents reported data eligible for analyses, including 337 peer-reviewed articles, 27 conference abstracts or presentations, and 148 documents from grey literature or supplementary searches. Data of recent HIV antibody testing were available for 67 countries and ever having had HCV antibody testing were available for 49 countries. Globally, an estimated 48·8% of people who inject drugs were recently tested for HIV antibodies (95% uncertainty interval [UI] 43·3-54·2%; range 0·9-86·0%), and 47·1% had ever been tested for HCV antibodies (95% UI 43·4-51·0%; range 0·0-93·3%). HCV RNA testing data were available from three countries. Coverage of HIV antibody testing was high (>75%) in four countries and for HCV antibody testing in 15 countries. The estimated uptake of current HIV treatment (18 countries) ranged from 2·6% to 81·9%, and the estimated uptake of ever having HCV treatment (23 countries) ranged from 1·8% to 88·6% across countries. Uptake of HIV treatment was high in two countries, and of HCV treatment in one country. HIV and HCV testing and treatment uptake among people who inject drugs was highly variable, and suboptimal in most countries. Strategies to improve access to HIV and HCV care among people who inject drugs and the availability of public health surveillance are urgently required. Australian National Health and Medical Research Council and UK National Institute for Health and Care Research Health Protection Research Unit in Behavioural Science and Evaluation.

Development of simple, rapid, and sensitive methods for detection of hepatitis C virus RNA from whole blood using reverse transcription loop-mediated isothermal amplification.

Hepatitis C virus (HCV) infection is an underdiagnosed global health problem. Diagnosis of current HCV infections typically requires testing for HCV RNA using high-complexity laboratory tests. Methods for the detection of HCV RNA that are simple, inexpensive, rapid, and compatible with use outside of a laboratory setting are very important in order to improve access to hepatitis C diagnostic testing and facilitate accelerated linkage to care. We developed and evaluated three simple workflows for extracting HCV RNA from small volumes of whole blood for use in a sensitive, pan-genotypic RT-LAMP assay. The water workflow uses osmotic stress to release HCV RNA and has a limit of detection of 4.3 log10(IU/mL) (95% CI 4.0-4.9). The heat workflow uses a heating step to release HCV RNA and has a limit of detection of 4.2 log10(IU/mL) (95% CI 3.8-5.1). The bead workflow, which uses chemical lysis of the sample and a streamlined paramagnetic solid phase reversible immobilization bead procedure for nucleic acid purification, has a limit of detection of 2.8 log10(IU/mL) (95% CI 2.5-3.4). When used to test whole blood spiked with HCV RNA-positive plasma samples in which most HCV levels were below 5.0 log10(IU/mL), the water, heat, and bead workflows detected HCV RNA in 69%, 75%, and 94% of samples, respectively. These workflows are compatible with visual lateral flow dipsticks, and each takes less than 60 min from sample to result. Each workflow can be performed with minimal and inexpensive equipment. With further procedural simplifications, these workflows may form the basis of assays for the point-of-care diagnosis of HCV infections.