We Must Do Better: Addressing HCV Treatment Barriers in Persons Who Inject Drugs in the United States.

The opioid epidemic in the United States, along with a lack of adequate harm reduction services, has contributed to a sharp rise in hepatitis C virus (HCV) infections. Despite considerable evidence of the effectiveness of HCV treatment in people who inject drugs (PWID), and recommendations from clinical guidelines to prioritize treatment in PWID, there are multiple barriers to broad uptake of HCV treatment. These barriers exist at the systems level, as well as at the level of medical providers and patients. Interventions to remove treatment barriers in the United States include harm reduction services, simplifying HCV testing algorithms, improved linkage to HCV care services, and application of new treatment models including colocating services at substance use disorder treatment programs. By following the lead of other countries who have addressed the barriers to HCV treatment, the United States has opportunities to do better in addressing the consequences of the opioid epidemic, including chronic HCV infection.

Hepatitis C elimination among people who inject drugs: Challenges and recommendations for action within a health systems framework.

The burden of hepatitis C infection is considerable among people who inject drugs (PWID), with an estimated prevalence of 39%, representing an estimated 6.1 million people who have recently injected drugs living with hepatitis C infection. As such, PWID are a priority population for enhancing prevention, testing, linkage to care, treatment and follow-up care in order to meet World Health Organization (WHO) hepatitis C elimination goals by 2030. There are many barriers to enhancing hepatitis C prevention and care among PWID including poor global coverage of harm reduction services, restrictive drug policies and criminalization of drug use, poor access to health services, low hepatitis C testing, linkage to care and treatment, restrictions for accessing DAA therapy, and the lack of national strategies and government investment to support WHO elimination goals. On 5 September 2017, the International Network of Hepatitis in Substance Users (INHSU) held a roundtable panel of international experts to discuss remaining challenges and future priorities for action from a health systems perspective. The WHO health systems framework comprises six core components: service delivery, health workforce, health information systems, medical procurement, health systems financing, and leadership and governance. Communication has been proposed as a seventh key element which promotes the central role of affected community engagement. This review paper presents recommended strategies for eliminating hepatitis C as a major public health threat among PWID and outlines future priorities for action within a health systems framework.

Incidence, determinants and outcomes of pregnancy-associated hepatitis B flares: A regional hospital-based cohort study.

BACKGROUND & AIMS: There is limited knowledge about hepatitis B virus (HBV) flare among pregnant women. We evaluated the incidence, determinants and outcomes of HBV flare in a multicultural cohort of pregnant HBV-infected women in the United States. METHODS: We performed a retrospective cohort study of pregnant hepatitis B surface antigen-positive women cared for at hospital-based clinics of 4 medical centres in Southeastern Pennsylvania from 2006 to 2015. The main outcome was incident HBV flare (alanine aminotransferase [ALT] ≥2 times upper limit of normal) during pregnancy or within 6 months after delivery. Among patients with flare, we determined development of jaundice (total bilirubin ≥2.5 mg/dL) and hepatic decompensation. Multivariable logistic regression was used to estimate odds ratios (ORs) of HBV flare for risk factors of interest, including timing of flare (during pregnancy versus post-delivery), nulliparity, younger age, HBV e antigen (HBeAg) status, and lack of anti-HBV therapy. RESULTS: Among 310 pregnant predominantly African HBV-infected women with 388 pregnancies, the incidence of HBV flare was 14% (95% CI, 10-18%) during pregnancy and 16% (95% CI, 11-24%) post-delivery. Jaundice developed in 12% and hepatic decompensation in 2%. Positive HBeAg was associated with HBV flare (OR, 2.55; 95% CI, 1.04-6.20). HBV DNA was measured in 55% of patients, and only 50% were referred for HBV specialty care. CONCLUSIONS: Pregnancy-associated hepatitis B flare occurred in 14% during pregnancy and 16% post-delivery and rarely led to hepatic decompensation. Positive HBeAg was the main risk factor identified. Women did not have adequate HBV monitoring or follow-up during pregnancy.

Access to Costly New Hepatitis C Drugs: Medicine, Money, and Advocacy.

Hepatitis C affects >3 million people in the United States, and often leads to end-stage liver disease or death. In 2014, several new drugs to treat hepatitic C virus received US Food and Drug Administration approval, with remarkable cure rates exceeding 90%. Medicaid, however, is rationing these drugs, and other insurers have restricted coverage due to their exorbitant costs and the large size of the population in need. These access barriers and disparities have resulted in national patient advocacy mobilization, US congressional inquiry, and legal challenges. The US Department of Health and Human Services has been urged to intervene. We propose the establishment of a federal program, analogous to AIDS Drug Assistance Programs, to reduce access barriers and facilitate focused price negotiations. The federal government may further undertake a nonvoluntary acquisition of the pharmaceutical patents pursuant to federal statutory authority and principles of eminent domain. Projections indicate this proposal could lower costs by 90% and eliminate rationing.

Results from a Geographically Focused, Community-Based HCV Screening, Linkage-to-Care and Patient Navigation Program.

BACKGROUND: Many of the five million Americans chronically infected with hepatitis C (HCV) are unaware of their infection and are not in care. OBJECTIVE: We implemented and evaluated HCV screening and linkage-to-care interventions in a community setting. DESIGN: We developed a comprehensive, community-based HCV screening and linkage-to-care program in a medically underserved neighborhood with high rates of HCV infection in Philadelphia, Pennsylvania. We provided patient navigation services to enroll uninsured patients in insurance programs, facilitate referrals from primary care physicians and link patients to an HCV infectious disease specialist with intention to treat and cure. PATIENTS: Philadelphia residents were recruited through street outreach. MAIN MEASURES: We measured anti-HCV seroprevalence and diagnosis, linkage and retention in care outcomes for chronically infected patients. KEY RESULTS: We screened 1,301 participants for HCV; anti-HCV seroprevalence was 3.9 % and 2.8% of all patients were chronically infected. Half of chronically infected patients were newly diagnosed; the remaining patients were aware of infection but not in care. We provided confirmatory RNA testing and results, assisted patients with attaining insurance and linked most chronically infected patients to a primary care provider. The biggest barrier to retaining patients in care was obtaining referrals for subspecialty providers; however, we obtained referrals for 64% of chronically infected participants and have retained most in subspecialty HCV care. Several have commenced treatment. CONCLUSIONS: Non-clinical screening programs with patient navigator services are an effective means to diagnose, link, retain and re-engage patients in HCV care. Eliminating referral requirements for subspecialty care might further enhance retention in care for patients chronically infected with HCV.

Geography should not be destiny: focusing HIV/AIDS implementation research and programs on microepidemics in US neighborhoods.

African Americans and Hispanics are disproportionately affected by the HIV/AIDS epidemic. Within the most heavily affected cities, a few neighborhoods account for a large share of new HIV infections. Addressing racial and economic disparities in HIV infection requires an implementation program and research agenda that assess the impact of HIV prevention interventions focused on increasing HIV testing, treatment, and retention in care in the most heavily affected neighborhoods in urban areas of the United States. Neighborhood-based implementation research should evaluate programs that focus on community mobilization, media campaigns, routine testing, linkage to and retention in care, and block-by-block outreach strategies.

Sofosbuvir: A Nucleotide NS5B Inhibitor for the Treatment of Chronic Hepatitis C Infection.

OBJECTIVE: To review the use of sofosbuvir for the treatment of chronic hepatitis C virus (HCV). DATA SOURCES: Review and nonreview articles were identified through MEDLINE (1996-April 2014), citations of articles, and meeting abstracts using keywords, including NS5B polymerase inhibitor, GS-7977, sofosbuvir, direct-acting antiviral (DAA), and others. STUDY SELECTION AND DATA EXTRACTION: Phase 1, 2, and 3 studies describing dose-ranging potential, pharmacokinetics, efficacy, safety, and tolerability of sofosbuvir were identified. DATA SYNTHESIS: Sofosbuvir is an NS5B polymerase inhibitor that was approved for use by the Food and Drug Administration in December 2013 for the treatment of chronic HCV in combination with pegylated interferon (peg-IFN) and ribavirin (RBV) for genotype 1. Additionally, it has been evaluated with other oral DAAs, such as simeprevir and others in the pipeline. It is not recommended as monotherapy because of lower sustained virological response (SVR) rates in clinical studies. Most of the treatment regimens are 12 weeks in duration; however, certain populations require a longer duration. Sofosbuvir has activity against all 6 genotypes, although most clinical trials evaluated genotypes 1 to 3. Sofosbuvir has a favorable safety and tolerability profile, making it a recommended first-line agent for chronic HCV infection. CONCLUSION: In clinical trials, 12 weeks of sofosbuvir with concomitant peg-IFN and RBV therapy in treatment-naïve and experienced HCV genotype 1 patients resulted in SVR rates of >90%. An all-oral regimen of sofosbuvir and RBV is highly effective for genotype 2 and 3 patients. Sofosbuvir was found to be tolerable with minimal adverse effects (AEs), and no treatment discontinuations occurred secondary to drug related AEs..

The Hepatitis C Care Cascade During the Direct-Acting Antiviral Era in a United States Commercially Insured Population.

Background: Periodic surveillance of the hepatitis C virus (HCV) care cascade is important for tracking progress toward HCV elimination goals, identifying gaps in care, and prioritizing resource allocation. In the pre-direct-acting antiviral (DAA) era, it was estimated that 50% of HCV-infected individuals were diagnosed and that 16% had been prescribed interferon-based therapy. Since then, few studies utilizing nationally representative data from the DAA era have been conducted in the United States. Methods: We performed a cross-sectional study to describe the HCV care cascade in the United States using the Optum de-identified Clinformatics® Data Mart Database to identify a nationally representative sample of commercially insured beneficiaries between January 1, 2014 and December 31, 2019. We estimated the number of HCV-viremic individuals in Optum based on national HCV prevalence estimates and determined the proportion who had: (1) recorded diagnosis of HCV infection, (2) recorded HCV diagnosis and underwent HCV RNA testing, (3) DAA treatment dispensed, and (4) assessment for cure. Results: Among 120,311 individuals estimated to have HCV viremia in Optum during the study period, 109,233 (90.8%; 95% CI, 90.6%-91.0%) had a recorded diagnosis of HCV infection, 75,549 (62.8%; 95% CI, 62.5%-63.1%) had a recorded diagnosis of HCV infection and underwent HCV RNA testing, 41,102 (34.2%; 95% CI, 33.9%-34.4%) were dispensed DAA treatment, and 25,760 (21.4%; 95% CI, 21.2%-21.6%) were assessed for cure. Conclusions: Gaps remain between the delivery of HCV-related care and national treatment goals among commercially insured adults. Efforts are needed to increase HCV treatment among people diagnosed with chronic HCV infection to achieve national elimination goals.

Methadone use is associated with increased levels of sCD14, immune activation, and inflammation during suppressed HIV infection.

Opioid use has negative effects on immune responses and may impair immune reconstitution in persons living with HIV (PLWH) infection undergoing antiretroviral treatment (ART). The effects of treatment with µ opioid receptor (MOR) agonists (e.g., methadone, MET) and antagonists (e.g., naltrexone, NTX) on immune reconstitution and immune activation in ART-suppressed PLWH have not been assessed in-depth. We studied the effects of methadone or naltrexone on measures of immune reconstitution and immune activation in a cross-sectional community cohort of 30 HIV-infected individuals receiving suppressive ART and medications for opioid use disorder (MOUD) (12 MET, 8 NTX and 10 controls). Plasma markers of inflammation and immune activation were measured using ELISA, Luminex, or Simoa. Plasma IgG glycosylation was assessed using capillary electrophoresis. Cell subsets and activation were studied using whole blood flow cytometry. Individuals in the MET group, but no in the NTX group, had higher plasma levels of inflammation and immune activation markers than controls. These markers include soluble CD14 (an independent predictor of morbidity and mortality during HIV infection), proinflammatory cytokines, and proinflammatory IgG glycans. This effect was independent of time on treatment. Our results indicate that methadone-based MOUD regimens may sustain immune activation and inflammation in ART-treated HIV-infected individuals. Our pilot study provides the foundation and rationale for future longitudinal functional studies of the impact of MOUD regimens on immune reconstitution and residual activation after ART-mediated suppression.

Priorities and recommended actions for how researchers, practitioners, policy makers, and the affected community can work together to improve access to hepatitis C care for people who use drugs.

It is estimated that 6.1 million people with recent injecting drug use (PWID) are living with hepatitis C virus (HCV). Although HCV-related morbidity and mortality among PWID continues to increase, the advent of direct acting antiviral (DAA) HCV regimens with cure rates >95% provides an opportunity to reverse the rising burden of disease. Additionally, given evidence that opioid substitution therapy and high-coverage needle and syringe programs can reduce HCV incidence by up to 80%, there is an opportunity to reduce HCV transmission with increased coverage of harm reduction services. However, there are significant patient, provider, health system, structural, and societal barriers that impede access to HCV prevention and care for PWID. The International Network on Hepatitis in Substance Users (INHSU), in collaboration with the Australasian Society for HIV, Viral Hepatitis, Sexual Health Medicine (ASHM), Harm Reduction International, the Canadian Network on Hepatitis C, Canadian Research Initiative in Substance Misuse, the National Viral Hepatitis Roundtable, Médecins du Monde and CATIE, held a roundtable discussion prior to the Harm Reduction Conference in Montreal, Canada on 13th May 2017 to discuss how to improve HCV prevention and care for PWID. Over 100 international researchers, practitioners, policy makers, advocates, and affected community members came together to discuss shared priorities for action, develop actionable next steps and to create partnerships to enable application of priorities. This paper highlights the key priority areas identified by participants including: enhancing global coverage of harm reduction services; addressing punitive drug policies; ensuring access to affordable HCV diagnostics and treatment; improving the evidence-base for HCV prevention, testing, linkage to care and treatment; implementing integrated HCV programs; advancing peer-based models of HCV care; and tackling social determinants of health inequalities for PWID. This paper also highlights the recommended actions for each priority identified by the participants from this roundtable.

Absolute Insurer Denial of Direct-Acting Antiviral Therapy for Hepatitis C: A National Specialty Pharmacy Cohort Study.

BACKGROUND: Despite the availability of new direct-acting antiviral (DAA) regimens, changes in DAA reimbursement criteria, and a public health focus on hepatitis C virus (HCV) elimination, it remains unclear if public and private insurers have increased access to these therapies over time. We evaluated changes in the incidence of absolute denial of DAA therapy over time and by insurance type. METHODS: We conducted a prospective cohort study among patients who had a DAA prescription submitted from January 2016 to April 2017 to Diplomat Pharmacy, Inc., which provides HCV pharmacy services across the United States. The main outcome was absolute denial of DAA prescription, defined as lack of fill approval by the insurer. We calculated the incidence of absolute denial, overall and by insurance type (Medicaid, Medicare, commercial), for the 16-month study period and each quarter. RESULTS: Among 9025 patients from 45 states prescribed a DAA regimen (4702 covered by Medicaid, 1821 Medicare, 2502 commercial insurance), 3200 (35.5%; 95% confidence interval, 34.5%-36.5%) were absolutely denied treatment. Absolute denial was more common among patients covered by commercial insurance (52.4%) than Medicaid (34.5%, P < .001) or Medicare (14.7%, P < .001). The incidence of absolute denial increased across each quarter of the study period, overall (27.7% in first quarter to 43.8% in last quarter; test for trend, P < .001) and for each insurance type (test for trend, P < .001 for each type). CONCLUSIONS: Despite the availability of new DAA regimens and changes in restrictions of these therapies, absolute denials of DAA regimens by insurers have remained high and increased over time, regardless of insurance type.

Hepatitis C risk assessment, testing and referral for treatment in urban primary care: role of race and ethnicity.

AIM: To determine rates of hepatitis C (HCV) risk factor ascertainment, testing, and referral in urban primary care practices, with particular attention to the effect of race and ethnicity. METHODS: Retrospective chart review from four primary care sites in Philadelphia; two academic primary care practices and two community clinics was performed. Demographics, HCV risk factors, and other risk exposure information were collected. RESULTS: Four thousand four hundred and seven charts were reviewed. Providers documented histories of injection drug use (IDU) and transfusion for less than 20% and 5% of patients, respectively. Only 55% of patients who admitted IDU were tested for HCV. Overall, minorities were more likely to have information regarding a risk factor documented than their white counterparts (79% vs 68%, P < 0.0001). Hispanics were less likely to have a risk factor history documented, compared to blacks and whites (P < 0.0001). Overall, minorities were less likely to be tested for HCV than whites in the presence of a known risk factor (23% vs 35%, P = 0.004). Among patients without documentation of risk factors, blacks and Hispanics were more likely to be tested than whites (20% and 24%, vs 13%, P < 0.005, respectively). CONCLUSION: (1) Documentation of an HCV risk factor history in urban primary care is uncommon, (2) Racial differences exist with respect to HCV risk factor ascertainment and testing, (3) Minority patients, positive for HCV, are less likely to be referred for subspecialty care and treatment. Overall, minorities are less likely to be tested for HCV than whites in the presence of a known risk factor.

Latent class analysis of acceptability and willingness to pay for self-HIV testing in a United States urban neighbourhood with high rates of HIV infection.

INTRODUCTION: Acceptability and willingness to both take and pay for HIV self-tests (HIVSTs) in US neighbourhoods with high rates of HIV infection are not well understood. METHODS: We surveyed 1,535 individuals about acceptability and willingness to take and pay for an HIVST in a predominately African American neighbourhood with 3% HIV seroprevalence. We recruited individuals presenting for HIV screening services in a community-based programme. Latent class analysis (LCA) grouped individuals with similar patterns of HIV-risk behaviours and determined which groups would be most willing to use and buy HIVSTs. RESULTS: Nearly 90% of respondents were willing to use an HIVST; 55% were willing to buy HIVSTs, but only 23% were willing to pay the market price of US $40. Four distinct groups emerged and were characterized by risk behaviours: (1) low risk (N = 324); (2) concurrent partnerships (N = 346); (3) incarceration and substance use (N = 293); and (4) condomless sex/multiple partners (N = 538). Individuals in the low-risk class were less willing to self-test compared to concurrent sexual partners (OR = 0.39, p = .003) and incarceration and substance use (OR = 0.46, p = .011) classes. There were no significant differences across classes in the amount individuals were willing to pay for an HIVST. CONCLUSION: HIVSTs were overwhelmingly acceptable but cost prohibitive; most participants were unwilling to pay the market rate of US $40. Subsidizing and implementing HIVST programmes in communities with high rates of infection present a public health opportunity, particularly among individuals reporting condomless sex with multiple partners, concurrent sexual partnerships and those with incarceration and substance use histories.

Routine HIV Screening in an Urban Community Health Center: Results from a Geographically Focused Implementation Science Program.

OBJECTIVE: CDC has recommended routine HIV screening since 2006. However, few community health centers (CHCs) routinely offer HIV screening. Research is needed to understand how to implement routine HIV screening programs, particularly in medically underserved neighborhoods with high rates of HIV infection. A routine HIV screening program was implemented and evaluated in a Philadelphia, Pennsylvania, neighborhood with high rates of HIV infection. METHODS: Implementation science is the study of methods to promote the integration of research findings and evidence into health-care policy and practice. Using an implementation science approach, the results of the program were evaluated by measuring acceptability, adoption, and penetration of routine HIV screening. RESULTS: A total of 5,878 individuals were screened during the program. HIV screening was highly accepted among clinic patients. In an initial needs assessment of 516 patients, 362 (70.2%) patients reported that they would accept testing if offered. Routine screening policies were adopted clinic-wide. Staff trainings, new electronic medical records that prompted staff members to offer screening and evaluate screening rates, and other continuing quality-improvement policies helped promote screenings. HIV screening offer rates improved from an estimated 5.0% of eligible patients at baseline in March 2012 to an estimated 59.3% of eligible patients in December 2014. However, only 5,878 of 13,827 (42.5%) patients who were offered screening accepted it, culminating in a 25.2% overall screening rate. Seventeen of the 5,878 patients tested positive, for a seropositivity rate of 0.3%. CONCLUSION: Routine HIV screening at CHCs in neighborhoods with high rates of HIV infection is feasible. Routine screening is an important tool to improve HIV care continuum outcomes and to address racial and geographic disparities in HIV infection.

Hepatitis C: How to fine-tune your approach.

Advances in drug therapy have made it possible to cure HCV infection. This article describes how best to screen, diagnose, and counsel these patients.