IMPORTANCE: To achieve hepatitis C elimination, treatment programs need to engage, treat, and cure people who inject drugs. OBJECTIVE: To compare a low-threshold, nonstigmatizing hepatitis C treatment program that was colocated at a syringe service program (accessible care) with facilitated referral to local clinicians through a patient navigation program (usual care). DESIGN, SETTING, AND PARTICIPANTS: This single-site randomized clinical trial was conducted at the Lower East Side Harm Reduction Center, a syringe service program in New York, New York, and included 167 participants who were hepatitis C virus RNA-positive and had injected drugs during the prior 90 days. Participants enrolled between July 2017 and March 2020. Data were analyzed after all patients completed 1 year of follow-up (after March 2021). INTERVENTIONS: Participants were randomized 1:1 to the accessible care or usual care arm. MAIN OUTCOMES AND MEASURES: The primary end point was achieving sustained virologic response within 12 months of enrollment. RESULTS: Among the 572 participants screened, 167 (mean [SD] age, 42.0 [10.6] years; 128 (77.6%) male, 36 (21.8%) female, and 1 (0.6) transgender individuals; 8 (4.8%) Black, 97 (58.5%) Hispanic, and 53 (32.1%) White individuals) met eligibility criteria and were enrolled, with 2 excluded postrandomization (n=165). Baseline characteristics were similar between the 2 arms. In the intention-to-treat analysis, 55 of 82 participants (67.1%) in the accessible care arm and 19 of 83 participants (22.9%) in the usual care arm achieved a sustained virologic response (P<.001). Loss to follow-up (12.2% [accessible care] and 16.9% [usual care]; P=.51) was similar in the 2 arms. Of the participants who received therapy, 55 of 64 (85.9%) and 19 of 22 (86.3%) achieved a sustained virologic response in the accessible care and usual care arms, respectively (P=.96). Significantly more participants in the accessible care arm achieved all steps in the care cascade, with the greatest attrition in the usual care arm seen in referral to hepatitis C virus clinician and attending clinical visit. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, among people who inject drugs with hepatitis C infection, significantly higher rates of cure were achieved using the accessible care model that focused on low-threshold, colocated, destigmatized, and flexible hepatitis C care compared with facilitated referral. To achieve hepatitis C elimination, expansion of treatment programs that are specifically geared toward engaging people who inject drugs is paramount. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03214679.

Clearance of acute infection with hepatitis C virus (HCV) is associated with the chr19q13.13 region containing the rs368234815 (TT/ΔG) polymorphism. We fine-mapped this region to detect possible causal variants that may contribute to HCV clearance. First, we performed sequencing of IFNL1-IFNL4 region in 64 individuals sampled according to rs368234815 genotype: TT/clearance (N = 16) and ΔG/persistent (N = 15) (genotype-outcome concordant) or TT/persistent (N = 19) and ΔG/clearance (N = 14) (discordant). 25 SNPs had a difference in counts of alternative allele >5 between clearance and persistence individuals. Then, we evaluated those markers in an association analysis of HCV clearance conditioning on rs368234815 in two groups of European (692 clearance/1 025 persistence) and African ancestry (320 clearance/1 515 persistence) individuals. 10/25 variants were associated (P < 0.05) in the conditioned analysis leaded by rs4803221 (P value = 4.9 × 10(-04)) and rs8099917 (P value = 5.5 × 10(-04)). In the European ancestry group, individuals with the haplotype rs368234815ΔG/rs4803221C were 1.7× more likely to clear than those with the rs368234815ΔG/rs4803221G haplotype (P value = 3.6 × 10(-05)). For another nearby SNP, the haplotype of rs368234815ΔG/rs8099917T was associated with HCV clearance compared to rs368234815ΔG/rs8099917G (OR: 1.6, P value = 1.8 × 10(-04)). We identified four possible causal variants: rs368234815, rs12982533, rs10612351 and rs4803221. Our results suggest a main signal of association represented by rs368234815, with contributions from rs4803221, and/or nearby SNPs including rs8099917.

BACKGROUND: We assessed prevalence of testing for HIV and hepatitis C virus (HCV) infection among persons who inject drugs (PWID). METHODS: Using a nationwide health insurance database for claims paid during 2010-2017, we identified PWID by using codes from the International Classification of Diseases, Current Procedural Terminology, and National Drug Codes directory. We then estimated the percentage of PWIDs tested for HIV or HCV within 1 year of an index encounter, and used multivariate logistic regression models to assess demographic and clinical factors associated with testing. RESULTS: Of 844 242 PWIDs, 71 938 (8.5%) were tested for HIV and 65 188 (7.7%) for HCV infections. Missed opportunities were independently associated with being male (ORs: HIV, 0.50 [95% CI, 0.49-0.50]; P < .001; HCV, 0.66 [95% CI, 0.65-0.72]; P < .001), rural residence (ORs: HIV, 0.67 [95% CI, 0.65-0.69]; P < .001; HCV, 0.75 [95% CI, 0.73-0.77]), and receiving services for skin infections or endocarditis (aORs: HIV, 0.91 [95% CI, 0.87-0.95]; P <.001; HCV, 0.90 [95% CI, 0.86-0.95]; P <.001). CONCLUSION: Approximately 90% of presumed PWIDs missed opportunities for HIV or HCV testing, especially male rural residents with claims for skin infections or endocarditis, commonly associated with injection drug use.

We appreciate Dr. Spaulding and colleagues’ thoughtful commentary on our article. We used national data to provide the most accurate estimate possible of the prevalence of hepatitis C among adults in the United States, but our estimate was dependent on the quality and completeness of the available data. We corrected for the omission of several high-prevalence populations from the National Health and Nutrition Examination Survey (NHANES), but no nationally representative studies of these populations exist. Spaulding and her colleagues raise a number of reasons why our study may underestimate the true prevalence of hepatitis C among incarcerated persons, but unfortunately, no nationwide data exist to assess the magnitude of these potential biases. According to 2016 Bureau of Justice Statistics data, most people arrested are detained in jails for short periods of time(1); thus, most of the number of persons cited in Dr. Spaulding’s reply would be eligible for NHANES sampling. We could not further adjust estimates for potential nonresponse bias beyond those addressed through standard NHANES sample weights without risk of double-counting prevalent cases. | | Varan et al.(2) data were excluded because we decided a priori to include only articles published more recently than those included in the incarcerated prevalence analysis from the Edlin et al. 2015(3) national hepatitis C virus prevalence estimate. With respect to the differential treatment of North Carolina and South Carolina from Schoenbachler et al. (4) (“study 6”), South Carolina data were excluded because “Initially, the South Carolina program targeted detainees…who had obtained tattoos in non-professional or unregulated settings.” Although testing was eventually expanded to include other detainees, Shoenbachler et al. did not indicate at what point that transition occurred or whether the expansion applied to all four South Carolina jails in the study or just one.(4) We determined that the targeted risk-based screening employed met our “sampling higher-risk subpopulations selectively” exclusion criteria, and consequently only included North Carolina data from Schoenbachler et al. in our analysis. | | Incarcerated populations bear a large and disproportionate hepatitis C burden, and incarceration provides an important opportunity to identify cases, provide life-saving curative treatment, and prevent transmission. The Centers for Disease Control and Prevention (CDC) is looking to other systems to collect data for prevention planning and providing more support to traditional and nontraditional surveillance systems both within and outside correctional facilities. Regardless of the exact number, prevention, testing, care, and treatment of incarcerated persons with or at risk for hepatitis C is an important priority for CDC and the nation.

Hepatitis C virus (HCV) infection is the most commonly reported bloodborne infection in the United States, causing substantial morbidity and mortality and costing billions of dollars annually. To update the estimated HCV prevalence among all adults aged >/=18 years in the United States, we analyzed 2013-2016 data from the National Health and Nutrition Examination Survey (NHANES) to estimate the prevalence of HCV in the noninstitutionalized civilian population and used a combination of literature reviews and population size estimation approaches to estimate the HCV prevalence and population sizes for four additional populations: incarcerated people, unsheltered homeless people, active-duty military personnel, and nursing home residents. We estimated that during 2013-2016 1.7% (95% confidence interval [CI], 1.4-2.0%) of all adults in the United States, approximately 4.1 (3.4-4.9) million persons, were HCV antibody-positive (indicating past or current infection) and that 1.0% (95% CI, 0.8-1.1%) of all adults, approximately 2.4 (2.0-2.8) million persons, were HCV RNA-positive (indicating current infection). This includes 3.7 million noninstitutionalized civilian adults in the United States with HCV antibodies and 2.1 million with HCV RNA and an estimated 0.38 million HCV antibody-positive persons and 0.25 million HCV RNA-positive persons not part of the 2013-2016 NHANES sampling frame. Conclusion: Over 2 million people in the United States had current HCV infection during 2013-2016; compared to past estimates based on similar methodology, HCV antibody prevalence may have increased, while RNA prevalence may have decreased, likely reflecting the combination of the opioid crisis, curative treatment for HCV infection, and mortality among the HCV-infected population; efforts on multiple fronts are needed to combat the evolving HCV epidemic, including increasing capacity for and access to HCV testing, linkage to care, and cure.

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 (HCV), 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 of 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 to 1.8 million) persons excluded from the NHANES sampling frame have HCV antibody, including 505,000 incarcerated people, 222,000 homeless people, 123,000 people living on Indian reservations, and 75,000 people in hospitals. Most are men. An estimated 0.8 million (range, 0.3 to 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. CONCLUSIONS: The number of U.S. residents who have been infected with hepatitis C is unknown but is probably at least 4.6 million (range, 3.4 to 6.0 million). Of these, at least 3.5 million (range, 2.5 to 4.7 million) are currently infected. Additional sources of potential underestimation suggest that the true prevalence could well be higher. This article is protected by copyright. All rights reserved.

Among vulnerable populations during an influenza pandemic are persons with or at risk for HIV infection, tuberculosis, or chronic viral hepatitis. HIV-infected persons have higher rates of hospitalization, prolonged illness, and increased mortality from influenza compared with the general population. Persons with tuberculosis and chronic viral hepatitis may also be at increased risk of morbidity and mortality from influenza because of altered immunity and chronic illness. These populations also face social and structural barriers that will be exacerbated by a pandemic. Existing infrastructure should be expanded and pandemic planning should include preparations to reduce the risks for these populations.