The urgent need to implement point-of-care RNA testing for hepatitis C virus to support elimination.

Hepatitis C virus (HCV) elimination is an important global public health goal. However, the United States (US) is not on track to meet the World Health Organization's 2030 targets for HCV elimination. Recently, the White House proposed an HCV elimination plan that includes point-of-care (POC) HCV RNA testing, which is currently in use in many countries, but is not approved in the US. POC HCV RNA testing is crucial for implementing community-based testing, and for enabling test-and-treat programs, assessing cure, and monitoring for reinfection.. In this commentary, we review the status of POC HCV RNA testing in the US, discuss factors that are needed for successful implementation, and issue specific public health and policy recommendations that would allow for the use of POC HCV RNA testing to support HCV elimination.

"Treated like a Human Being": perspectives of people who inject drugs attending low-threshold HCV treatment at a syringe service program in New York City.

BACKGROUND: Hepatitis C virus (HCV) treatment can effectively cure HCV among people who inject drugs (PWID). Perspectives of PWID treated in innovative models can reveal program features that address barriers to treatment, and guide implementation of similar models. METHODS: We interviewed 29 participants in the intervention arm of a randomized trial. The trial enrolled PWID with HCV in New York City from 2017 to 2020 and tested the effectiveness of a low-threshold HCV treatment model at a syringe services program. Participants were purposively sampled and interviewed in English or Spanish. The interview guide focused on prior experiences with HCV testing and treatment, and experiences during the trial. Interviews were inductively coded and analyzed using thematic analysis. RESULTS: Before enrollment, participants reported being tested for HCV in settings such as prison, drug treatment, and emergency rooms. Treatment was delayed because of not being seen as urgent by providers. Participants reported low self-efficacy, competing priorities, and systemic barriers to treatment such as insurance, waiting lists, and criminal-legal interactions. Stigma was a major factor. Treatment during the trial was facilitated through respect from staff, which overcame stigma. The flexible care model (allowing walk-ins and missed appointments) helped mitigate logistical barriers. The willingness of the staff to address social determinants of health was highly valued. CONCLUSION: Our findings highlight the need for low-threshold programs with nonjudgmental behavior from program staff, and flexibility to adapt to participants' needs. Social determinants of health remain a significant barrier, but programs' efforts to address these factors can engender trust and facilitate treatment. Trial registration NCT03214679.

Hepatitis C testing and treatment uptake among young people who use opioids in New York City: A cross-sectional study.

Young people who use drugs have a rising hepatitis C (HCV) incidence in the United States, but they may face barriers to testing and treatment adoption due to stigma. We conducted a cross-sectional study of New York City residents aged 18-29 years who reported non-medical prescription opioid and/or heroin use in the past 30 days. Participants were recruited from the community between 2014-2016 via respondent-driven sampling. Participants completed an in-person structured survey that included questions about HCV testing and treatment and received HCV antibody testing. There were 539 respondents: 353 people who inject drugs (PWID) and 186 non-PWID. For PWID, median age was 25 years, 65% were male and 73% non-Hispanic White. For non-PWID, median age was 23 years, 73% were male and 39% non-Hispanic White. 20% of PWID and 54% of non-PWID had never been tested for HCV (P < .001). Years since first injection (aOR 1.16, CI: 1.02-1.32, P = .02) and history of substance use treatment (aOR 3.17, CI: 1.53-6.61, P = .02) were associated with prior testing among PWID. The seroprevalence of HCV among PWID was 25%, adjusted for sampling weights. Of the 75 who were aware of their HCV-positive status, 53% had received HCV-related medical care, and 28% had initiated treatment. HCV prevalence among young PWID is high, and many have never been tested. Injection experience and treatment engagement is associated with testing. Interventions to increase testing earlier in injection careers, and to improve linkage to HCV treatment, will be critical for young PWID.

Toward a more accurate estimate of the prevalence of hepatitis C in the United States.

UNLABELLED: Data from the 2003-2010 National Health and Nutrition Examination Survey (NHANES) indicate that about 3.6 million people in the United States have antibodies to the hepatitis C virus, of whom 2.7 million are currently infected. NHANES, however, excludes several high-risk populations from its sampling frame, including people who are incarcerated, homeless, or hospitalized; nursing home residents; active-duty military personnel; and people living on Indian reservations. We undertook a systematic review of peer-reviewed literature and sought out unpublished presentations and data to estimate the prevalence of hepatitis C in these excluded populations and in turn improve the estimate of the number of people with hepatitis C in the United States. The available data do not support a precise result, but we estimated that 1.0 million (range 0.4 million-1.8 million) persons excluded from the NHANES sampling frame have hepatitis C virus antibody, including 500,000 incarcerated people, 220,000 homeless people, 120,000 people living on Indian reservations, and 75,000 people in hospitals. Most are men. An estimated 0.8 million (range 0.3 million-1.5 million) are currently infected. Several additional sources of underestimation, including nonresponse bias and the underrepresentation of other groups at increased risk of hepatitis C that are not excluded from the NHANES sampling frame, were not addressed in this study. CONCLUSION: The number of US residents who have been infected with hepatitis C is unknown but is probably at least 4.6 million (range 3.4 million-6.0 million), and of these, at least 3.5 million (range 2.5 million-4.7 million) are currently infected; additional sources of potential underestimation suggest that the true prevalence could well be higher.

Rapid Treatment Initiation for Hepatitis C Virus Infection: Potential Benefits, Current Limitations, and Real-World Examples.

The science for rapid treatment initiation for hepatitis C virus infection is in place. Easy and quick diagnostic tools can provide results within an hour. Necessary assessment before treatment initiation is now minimal and manageable. Treatment has a low dose burden and high tolerability. Although the critical components for rapid treatment are accessible, certain barriers prevent wider utilization, including insurance restrictions and delays in the health care system. Rapid treatment initiation can improve linkage to care by addressing many barriers to care at once, which is essential for achieving a care plateau. Young people with low health care engagement, finitely engaged people (eg, those who are incarcerated), or people with high-risk injection drug behavior, and thereby high risk for transmission of hepatitis C virus, can benefit the most from rapid treatment. Several innovative care models have demonstrated the potential for rapid treatment initiation by overcoming barriers to care with rapid diagnostic testing, decentralization, and simplification. Expanding these models is likely to be an important component for the elimination of hepatitis C virus infection. This article reviews the current motivation for rapid treatment initiation for hepatitis C virus infection and published literature describing rapid treatment initiation models.

Cost of providing co-located hepatitis C treatment at a syringe service program exceeds potential reimbursement: Results from a clinical trial.

Background: Co-located hepatitis C treatment at syringe service programs (SSP) is an emerging model of care for people who inject drugs (PWID). Implementation of these models can be informed by understanding the program costs. Methods: We conducted an economic evaluation of a hepatitis C treatment intervention at an SSP in New York City implemented as one arm of a randomized trial from 2017 to 2021. Start-up and operating costs were determined from the treatment program's perspective using micro-costing and were compared to potential Medicaid reimbursement. We applied nationally representative unit costs and wage rates. Results are reported in 2020 USD. Results: The treatment program was staffed by one physician and one care coordinator. Participants were offered hepatitis C clinical evaluation and treatment, a 45-min reinfection prevention education session, and additional care coordination as needed. The trial enrolled 84 PWID with hepatitis C in the intervention arm; 64 initiated treatment and 55 achieved sustained virological response. Start-up costs including training and equipment totaled $4677. Overhead costs including rent, utilities and software totaled $2229 per month. Clinical and care coordination totaled $4867 per participant, of which $3722 was care coordination. The total cost excluding startup was $6035 per enrolled participant and $7921 per treated participant; estimated potential reimbursement was $628 per enrolled participant. Conclusion: Our results provide insight to US-based SSPs seeking to provide co-located hepatitis C care and highlight the intensive care coordination services provided. Successful implementation likely requires funding sources beyond health insurers or substantial changes to insurance reimbursement for care coordination.

Hepatitis C virus risk among young people who inject drugs.

Background: Injection drug use (IDU) is the leading risk factor for hepatitis C virus (HCV) transmission in the U.S. While the general risk factors for HCV transmission are known, there is limited work on how these factors interact and impact young people who inject drugs (YPWID). Methods: Project data were drawn from a study of 539 New York City (NYC) residents ages 18-29 who were recruited via Respondent-Driven Sampling and, reported past-month non-medical use of prescription opioids and/or heroin. Analyses are based on a subsample of 337 (62%) who reported injecting any drug in the past 12 months. All variables were assessed via self-report, except HCV status, which was established via rapid antibody testing. Integrating the observed statistical associations with extant literature on HCV risk, we also developed a qualitative system dynamics (SD) model to use as a supplemental data visualization tool to explore plausible pathways and interactions among key risk and protective factors for HCV. Results: Results showed a 31% HCV antibody prevalence with an overall incidence of 10 per 100 person-years. HCV status was independently correlated with having shared cookers with two or more people (AOR = 2.17); injected drugs 4-6 years (AOR = 2.49) and 7 or more years (AOR = 4.95); lifetime homelessness (AOR = 2.52); and having been incarcerated two or more times (AOR = 1.99). These outcomes along with the extant literature on HCV risk were used to develop the qualitative SD model, which describes a causal hypothesis around non-linearities and feedback loop structures underlying the spread of HCV among YPWID. Conclusions: Despite ongoing harm reduction efforts, close to a third of YPWID in the community sample have been exposed to HCV, have risks for injection drug use, and face challenges with structural factors that may be preventing adequate intervention. The qualitative SD model explores these issues and contributes to a better understanding of how these various risk factors interact and what policies could potentially be effective in reducing HCV infections.

Comorbidity and clinical factors associated with COVID-19 critical illness and mortality at a large public hospital in New York City in the early phase of the pandemic (March-April 2020).

BACKGROUND: Despite evidence of socio-demographic disparities in outcomes of COVID-19, little is known about characteristics and clinical outcomes of patients admitted to public hospitals during the COVID-19 outbreak. OBJECTIVE: To assess demographics, comorbid conditions, and clinical factors associated with critical illness and mortality among patients diagnosed with COVID-19 at a public hospital in New York City (NYC) during the first month of the COVID-19 outbreak. DESIGN: Retrospective chart review of patients diagnosed with COVID-19 admitted to NYC Health + Hospitals / Bellevue Hospital from March 9th to April 8th, 2020. RESULTS: A total of 337 patients were diagnosed with COVID-19 during the study period. Primary analyses were conducted among those requiring supplemental oxygen (n = 270); half of these patients (135) were admitted to the intensive care unit (ICU). A majority were male (67.4%) and the median age was 58 years. Approximately one-third (32.6%) of hypoxic patients managed outside the ICU required non-rebreather or non-invasive ventilation. Requirement of renal replacement therapy occurred in 42.3% of ICU patients without baseline end-stage renal disease. Overall, 30-day mortality among hypoxic patients was 28.9% (53.3% in the ICU, 4.4% outside the ICU). In adjusted analyses, risk factors associated with mortality included dementia (adjusted risk ratio (aRR) 2.11 95%CI 1.50-2.96), age 65 or older (aRR 1.97, 95%CI 1.31-2.95), obesity (aRR 1.37, 95%CI 1.07-1.74), and male sex (aRR 1.32, 95%CI 1.04-1.70). CONCLUSION: COVID-19 demonstrated severe morbidity and mortality in critically ill patients. Modifications in care delivery outside the ICU allowed the hospital to effectively care for a surge of critically ill and severely hypoxic patients.

Contact tracing for hepatitis C: The case for novel screening strategies as we strive for viral elimination.

Contact tracing has been a key element of the public health response to infectious diseases for decades. These practices have been powerful in slowing the spread of tuberculosis, HIV, and other sexually transmitted infections. Despite success in other contexts, contact tracing for hepatitis C virus (HCV) has historically been considered infeasible because of a long asymptomatic period, which often makes it difficult to pinpoint the time of acquisition. Additionally, individuals may be reluctant to identify injecting partners because of stigma or fear of criminal repercussions. However, multiple factors - including the improved curability of HCV with advances in direct acting antiviral agents (DAAs), the implementation of age-based screening, and the current opioid epidemic -- have led to rapid changes in the landscape of HCV. HCV is increasingly concentrated among young people who inject drugs (PWID), many of whom are inadequately being reached by current screening practices. With the shift in the population most at risk for HCV and the fundamental changes in how we manage this disease, it's time to also rethink the public health response in identifying and informing those who may have been exposed. Contact tracing programs for HCV can augment existing screening strategies to provide curative treatment for patients and their partners, prevent reciprocal transmission of HCV between risk partners and within networks, and ultimately reach individuals who aren't yet engaged in healthcare and harm reduction. While there remain limitations to contact tracing for HCV, it has the potential to be a powerful tool in slowing the spread of the virus as we attempt to achieve viral elimination.

Hepatitis C Treatment Outcomes for People Who Inject Drugs Treated in an Accessible Care Program Located at a Syringe Service Program.

Hepatitis C virus (HCV) is a significant public health problem that disproportionately afflicts people who inject drugs. We describe outcomes of HCV treatment co-located within a syringe services program (SSP). Fifty-three participants started therapy, and 91% achieved sustained virologic response. SSPs provide an effective venue for HCV treatment.

Case Report: A Cluster of Three Leptospirosis Cases in a New York City Abattoir and an Unusual Complication in the Index Case.

We report the case of a 46-year-old male abattoir worker who developed myalgias, shortness of breath, and irritability 2 weeks after sustaining a laceration to the hand with a knife at work. During his hospital evaluation for septic shock he was noted to be febrile, hypotensive, profoundly jaundiced with aseptic meningitis, and renal failure, and was diagnosed with Leptospirosis interrogans infection confirmed by serum and urine polymerase chain reaction. After standard antibiotic therapy and recovery from severe clinical illness, he developed unilateral orchitis with pyuria secondary to leptospirosis, a well-established complication in the veterinary literature, but of which we offer the first report in humans in the English literature. The case presented was also the index case that uncovered a cluster outbreak of leptospirosis in New York City during the winter of 2016-2017, involving a total of three patients who lived or worked within a block of the abattoir. Two patients survived whereas the third died of pulmonary hemorrhage shortly after seeking medical care.

Glycated Hemoglobin A(1c) as screening for diabetes mellitus in HIV-infected individuals.

The American Diabetes Association now recommends hemoglobin A(1c) (HbA(1c)) screening for the diagnosis of diabetes. It has been reported that HbA(1c) levels underestimate glycemic levels in HIV-infected persons. We examined the performance of HbA(1c) as a screening test for diabetes in a group of HIV-infected people without diabetes. We conducted a retrospective cross-sectional cohort study among HIV-infected patients determining the sensitivity and specificity of HbA(1c) as a screening test compared to fasting blood glucose (FBG). The effect of treatment regimen on the relationship between HbA(1c) and FBG was assessed by multiple linear regressions. Twenty-two of the 395 patients included in the study were newly diagnosed with diabetes based on FBG≥126 mg/dL. Using a cutoff of HbA(1c)≥6.5%, HbA(1c) had a sensitivity of 40.9% and specificity of 97.5% for identification of incident diabetes. At an HbA(1c) level of 5.8% the product of sensitivity and specificity was maximized, with values of 88.8% and 77.5% respectively. Higher mean cell volume (MCV) values (p=0.02) and current use of a non-nucleoside reverse transcriptase inhibitors (NNRTIs; p=0.02) significantly increased the slope, while PI use significantly decreased the slope (p<0.001), of the linear regression of HbA(1c) compared to FBG. Tenofovir use did not significantly alter the slope or y-intercept of the line. Among HIV-infected nondiabetic patients, HbA(1c) is insensitive, although highly specific for diagnosing diabetes. Current antiretroviral (ART) use has significant and variable influence on the relationship between HbA(1c) and FBG. The use of HbA(1c) in conjunction with FBG may be the best modality to screen for diabetes.

Antiretroviral therapy and cardiovascular risk: are some medications cardioprotective?

PURPOSE OF REVIEW: This review addresses the associations between coronary heart disease and antiretroviral medications, with a specific focus on medications that appear to have neutral or positive effects on coronary heart disease risk factors. RECENT FINDINGS: Studies have linked combination antiretroviral therapy with an increased risk of coronary heart disease. Often implicated are the effects of these medications on the metabolic risk factors for coronary heart disease, specifically lipids and glucose homeostasis. Many newer antiretrovirals have fewer metabolic side effects, and antiretrovirals in general may be cardioprotective by reducing inflammation. Whether use of specific antiretroviral regimens will translate into improved cardiovascular outcomes remains to be seen. SUMMARY: Some antiretrovirals appear to be at least neutral with regards to coronary heart disease risk, but it is not clear if any are truly cardioprotective. Nonetheless, it is prudent to consider regimens with limited metabolic side effects in patients with pre-established coronary heart disease risk.