Access To Direct-acting Antivirals Research Articles

Cost-Effectiveness of Strategies for Treatment Timing for Perinatally Acquired Hepatitis C Virus

Prevalence of chronic hepatitis C virus (HCV) infection among pregnant people is increasing in the US. HCV is transmitted vertically in 7% to 8% of births. Direct-acting antiviral (DAA) therapy was recently approved for children with HCV who are 3 years or older. The clinical and economic impacts of early DAA therapy for young children with HCV, compared with treating at older ages, are unknown. To develop a state-transition model to project clinical and economic outcomes for children with perinatally acquired HCV to investigate the cost-effectiveness of treating at various ages. The study team modeled the natural history of perinatally acquired HCV to simulate disease progression and costs of a simulated a cohort of 1000 US children with HCV from 3 years old through death. Added data were analyzed January 5, 2021, through July 1, 2022. The study compared strategies offering 8 weeks of DAA therapy at 3, 6, 12, or 18 years old, as well as a comparator of never treating HCV. Outcomes of interest include life expectancy from 3 years and average lifetime per-person health care costs. Other clinical outcomes include cases of cirrhosis, decompensated cirrhosis, and hepatocellular carcinoma (HCC). The study team projected that treating HCV at 3 years old was associated with lower mean lifetime per-person health care costs ($148 162) than deferring treatment until 6 years old ($164 292), 12 years old ($171 909), or 18 years old ($195 374). Projected life expectancy was longest when treating at 3 years old (78.36 life years [LYs]) and decreased with treatment deferral until 6 years old (76.10 LYs), 12 years old (75.99 LYs), and 18 years old (75.46 LYs). In a cohort of 1000 children with perinatally acquired HCV, treating at 3 years old prevented 89 projected cases of cirrhosis, 27 cases of HCC, and 74 liver-related deaths compared with deferring treatment until 6 years old. In sensitivity analyses, increasing loss to follow-up led to even greater clinical benefits and cost savings with earlier treatment. These study results showed that DAA therapy for 3-year-old children was projected to reduce health care costs and increase survival compared with deferral until age 6 years or older. Measures to increase DAA access for young children will be important to realizing these benefits.

Policies for Expanding Hepatitis C Testing and Treatment in United States Prisons and Jails

Hepatitis C virus (HCV) is highly prevalent in United States prisons and jails. In prisons and jails, rates of infection are ten to twenty times greater than national levels. And, more than thirty percent of all people living with HCV in the United States will spend time in prisons and jails in any given year. Rates are especially high among people who inject drugs (PWID), a population whose members are also likely to move between carceral settings and the community. Thus, addressing HCV among incarcerated populations would have a significant effect on the virus’s transmission both in and out of confinement and is a crucial part of any HCV elimination strategy. Safe and effective HCV treatment is available. Direct-acting antivirals (DAAs) offered in an eight to twelve week course of oral treatment cure HCV in more than ninety percent of cases. Widespread testing and treatment in prisons and widespread testing and treatment or linkage to community care in jails are essential public health approaches. But testing and treatment in confinement lags behind medical guidance and public health recommendations. People incarcerated in prisons and detained in jails are entitled to adequate health care, and the U.S. Constitution prohibits deliberate indifference to their serious medical needs. In recent years, lawsuits filed by people with HCV in carceral facilities across the country have alleged violations of federal law for failure to provide DAA treatment. Although litigation results have been mixed, settlement agreements in states across the country have expanded HCV testing and broadened access to DAA treatment. These settlement agreements reflect a growing understanding that widespread testing and treatment is cost-effective, avoid the harmful health consequences of disease progression, and meaningfully reduce community transmission. This paper recommends model policies for prisons and jails to expand HCV testing and DAA treatment. The policy recommendations draw from relevant settlement agreements and current medical guidelines, supplemented by input from public health experts, medical professionals, and advocates. The paper proceeds as follows: • Part I describes the HCV epidemic in United States prisons and jails, the recent sea change in treatment protocols, and relevant clinical guidance and public health recommendations. • Part II sets out the legal landscape, including governing federal law and judicial decisions interpreting that law in this context, and describes settlement agreements in class action lawsuits addressing DAA access. • Finally, Part III offers model policies for prisons and jails to expand testing and treatment and to support successful outcomes for people with HCV in their custody.

From Prioritization to Universal Treatment: Successes and Challenges of Hepatitis C Virus Elimination in Italy.

Italy has had the highest prevalence of hepatitis C virus (HCV) infection and mortality from HCV-related liver cancer in Europe. Although direct-acting antivirals (DAA) were initially restricted to persons with advanced fibrosis, their use has since been extended to all infected individuals; more than 244 000 persons have been treated to date. HCV liver-related mortality is expected to decline by 75% by 2030, achieving the World Health Organization target for mortality. However, Italy risks failing to meet the overall goal of eliminating HCV infection by 2030. In this light, €71.5 million have been allocated for screening initially specific target populations (persons who inject drugs, prison inmates, and the 1969-1989 birth cohort). Herein, we outline the challenges and recommendations for how to move Italy toward HCV elimination, including expanding screening programs in other populations, increasing awareness through strategic communication, sustaining DAA access, and tailoring care models to meet the needs of key populations.

The impact of expanded access to direct acting antivirals for Hepatitis C virus on patient outcomes in Canada.

Hepatitis C virus (HCV) has high global prevalence and can lead to liver complications and death. Access to direct-acting antivirals (DAAs) in Canada increased following several policy changes, however the real-world impact of expanded DAA access and increased use of these drugs is unknown. We aimed to determine the early change in rates of HCV-related hospitalizations overall and HCV-related hospitalizations with hepatocellular carcinoma (HCC) after expanded DAA access. We conducted a population-based time series analysis using national administrative health databases in Canada. Rates of HCV-related hospitalizations and HCV-related hospitalizations with HCC were enumerated monthly between April 2006 and March 2020. We used Autoregressive Integrated Moving Average (ARIMA) models with ramp functions in October 2014 and January 2017 to evaluate the impact of policies to expand DAA access on hospitalization outcomes. Rates of HCV-related hospitalizations in Canada increased between 2006 and 2014, and gradually declined thereafter. The decrease after October 2014, or the first policy change, was significant (p = 0.0355), but no further change was found after the second policy change in 2017 (p = 0.2567). HCV-related hospitalizations with HCC increased until end of 2013, followed by a plateau, before declining in 2016. No significant shifts were found after the first policy change in 2014 (p = 0.1291) nor the second policy change in 2017 (p = 0.6324). Subgroup analyses revealed that those aged 50-64 and males had observable declines in rates of HCV-related hospitalizations in the year prior to the first policy change. Expanding DAA access was associated with a drop in HCV-related hospitalizations in the overall Canadian population coinciding with the 2014 policy change. In light of the time required for HCV-related complications to manifest, continued ongoing research examining the real-world effectiveness of DAAs is required.

Hepatitis C donor positive to recipient negative solid organ transplants: Early direct acting antiviral insurance approval rates with and without documented viremia

BackgroundCurrent guidelines support early initiation of direct-acting antivirals (DAA) in hepatitis C virus (HCV) donor positive and recipient negative (D+/R-) solid organ transplants (SOTs). According to experts, access to DAA therapy is a key barrier to early treatment. MethodsThis single-center, retrospective study assessed the rate of DAA prescription approval with or without confirmed HCV viremia, time to approval, and reasons for denial in HCV D+/R- SOTs. ResultsAll 51 patients received insurance approval for DAA therapy following transplantation regardless of confirmed HCV viremia at time of prior authorization (PA) submission. Same day PA approval was obtained in 51% of cases. Appeals received approval within a median of 2 days from submission. ConclusionOur findings suggest confirmed HCV viremia may not be as significant of a barrier to DAA access and may encourage other health systems to consider early initiation of DAA therapy in their HCV D+/R- transplants.

Treatment as prevention effect of direct-acting antivirals on primary hepatitis C virus incidence: findings from a multinational cohort between 2010 and 2019

Broad direct-acting antiviral (DAA) access may reduce hepatitis C virus (HCV) incidence through a "treatment as prevention" (TasP) effect. We assessed changes in primary HCV incidence following DAA access among people living with HIV (PLHIV). We used pooled individual-level data from six cohorts from the International Collaboration on Hepatitis C Elimination in HIV Cohorts (InCHEHC). Follow-up started from the first recorded negative HCV antibody test date and ended at last negative antibody test or estimated infection date. Follow-up was restricted to 2010-2019. We used segmented Poisson regression to model trends across pre-, limited- (i.e., restrictions on access) and broad-DAA access periods. Overall, 45,942 participants had at least one HCV antibody negative result and follow-up between 2010 and 2019. We observed 2042 incident HCV infections over 248,189 person-years (PY). Pooled incidence decreased from 0.91 per 100 PY in 2015 to 0.41 per 100 PY in 2019. Compared to the average pre-DAA period incidence (0.90 per 100 PY), average incidence was similar during the limited-DAA access period (Incidence rate ratio [IRR]=0.98; 95%CI=0.87, 1.11), and 52% lower during the broad-DAA access period (IRR=0.48; 95%CI=0.42, 0.52). The average annual decline in HCV incidence was 2% in the pre-DAA period; an additional 9% annual decline in incidence was observed during the limited-DAA access period (IRR=0.91; 95%CI=0.82, 1.00) and a further 20% decline in the broad-DAA access period (IRR=0.80, 95%CI=0.73, 0.89). Our findings suggest that broad DAA access has a TasP effect on primary HCV incidence among PLHIV. Based on the initial years of DAA availability, the countries in the InCHEHC collaboration are on track to meet the World Health Organization's 80% HCV incidence reduction target for PLHIV by2030. This study was funded by the Australian Government National Health and Medical Research Council (Grant number GNT1132902).

Disparities in Access to Hepatitis C Treatment Among Arizona Medicaid Beneficiaries With Chronic Hepatitis C.

High costs of direct-acting antivirals (DAAs) have led to their restricted access for patients with hepatitis C virus (HCV). The aim was to assess how HCV treatment access and predictors of HCV treatment changed in the post-DAA period compared with pre-DAA period. A retrospective cohort study using Arizona Medicaid data was conducted for patients with HCV to compare treatment initiation rates between pre-DAA (January 2008-October 2013) and post-DAA (November 2013-December 2018) periods. Multivariable logistic regression was used, controlling for demographic and clinical variables. Twenty-four thousand and ninety and 28,756 patients during the pre-DAA and post-DAA periods were identified. Overall, 12.6% were treated in the post-DAA period compared with 7.8% in the pre-DAA period ( P <0.001). The relative increase in the HCV treatment initiation rate from the pre-DAA to the post-DAA period was significant greater for Black beneficiaries compared with White beneficiaries ( P =0.002). Hispanic beneficiaries were less likely to be treated in the post-DAA period [adjusted odds ratios (aOR): 0.88; CI: 0.79-0.98] compared with White beneficiaries. Those with mental illness (aOR: 0.71; 95% CI: 0.63-0.80) and substance use disorders (aOR: 0.63; 95% CI: 0.58-0.68) were less likely to be treated in the post-DAA period. Although treatment initiation increased and disparities for Black beneficiaries compared with White beneficiaries attenuated in the post-DAA period, only 13% of Arizona Medicaid patients with HCV received DAA treatment. Disparities in DAA access remained among Hispanic patients and those with mental illness and substance use disorders.

The 'Viennese epidemic' of acute HCV in the era of direct-acting antivirals.

The recently reported epidemic of acute hepatitis C virus (HCV) infections —observed predominantly among men who have sex with men (MSM)—may now decline due to wide availability of direct‐acting antivirals (DAAs). This study aimed to investigate the current trends of acute hepatitis C in Vienna. Patients presenting with acute hepatitis C between 01/2007 and12/2020 at the Vienna General Hospital were retrospectively enrolled and followed after virologic clearance/eradication. The introduction of unrestricted DAA access after 09/17 defined the ‘DAA era’, as compared to the ‘pre‐DAA era’ prior to 09/17. We identified 134 acute hepatitis C cases in 119 patients with a mean age of 39 ± 9 years at inclusion. The majority of patients were male (92%), HIV‐positive (88%) and MSM (85%). In the DAA era, a history of prior chronic HCV infection at inclusion was found in 24% (11/46) compared to 7% (5/73) in the pre‐DAA era (p = .012). The annual rate of acute hepatitis C cases increased in the DAA era (17.11 per year) compared to the pre‐DAA era (7.76 per year). The DAA era included an AHC‐genotype‐2 cluster and more HIV‐negative acute hepatitis C cases (0% (0/73) vs. 30% (14/46), p < .001). Patients were followed after spontaneous clearance or sustained virologic treatment response (SVR) for a total of 251.88 patient‐years (median 1.39 years per patient). In the DAA era, we recorded 15 acute hepatitis C‐reinfections — corresponding to an incidence rate of 5.96 (95% CI: 3.57–9.66) reinfections per 100‐patient‐years. We continue to observe a high incidence of acute hepatitis C in Vienna in the DAA era—primarily among HIV‐positive MSM, but increasingly also in HIV‐negative MSM.

Access to hepatitis C direct-acting antiviral therapy in hepatitis C-positive donor to hepatitis C-negative recipient solid-organ transplantation in a real-world setting

BackgroundEmerging data supports expanding the solid organ donor pool with transplantation from hepatitis C virus (HCV)-positive donors into HCV-negative recipients. However, concerns exist regarding the ability to access direct-acting antivirals (DAAs) post-transplant in a real-world setting. MethodsThis single-center, retrospective study evaluated DAA access rates, time to first dose, and patient cost in donor-derived HCV solid-organ transplant recipients utilizing an integrated specialty pharmacy process. ResultsAmong 91 patients, all accessed DAAs through prescription insurance (97%) or patient assistance programs (3%). Of those who received DAAs through insurance, only 65% received approval on initial insurance submission. Median time from transplant to first dose was 45d [IQR 34–66]. The on-site specialty pharmacy was used by 69% of patients. Copay assistance programs reduced the median monthly patient cost from $1914 [range $7-7536] to $0 [range $0–5]. ConclusionOur findings indicate that access to DAAs in donor-derived HCV post-transplant is achievable and affordable; however, significant added administrative efforts may be required for insurance approval as well as obtaining copay assistance, which is a limited resource.

Responsible Inclusion of Pregnant Individuals in Eradicating HCV.

HCV infections have increased in recent years due to injection drug use and the opioid epidemic. Simultaneously, HCV cure has become a reality, with the advent of direct-acting antivirals (DAAs) and expansion of treatment programs. As a result, HCV screening recommendations now include all adults, including pregnant individuals; and many countries have endorsed widespread DAA access as a strategy to achieve HCV eradication. However, almost universally, pregnant individuals have been systematically excluded from HCV clinical research and treatment programs. This omission runs counter to public health strategies focused on elimination of HCV but is consistent with a historical pattern of exclusion of pregnant individuals from research. Our systematic review of publications on HCV treatment with DAAs in pregnancy revealed only one interventional study, which evaluated sofosbuvir/ledipasvir in 8 pregnant individuals. Given the paucity of research on this issue of great public health importance, we aimed to appraise the current landscape of HCV research/treatment and analyze the ethical considerations for responsibly including pregnant individuals. We propose that pregnancy may be an opportune time to offer HCV treatment given improved access, motivation, and other health care monitoring occurring in the antenatal period. Moreover, treatment of pregnant individuals may support the goal of eliminating perinatal HCV transmission and overcome the established challenges with transitioning care after delivery. The exclusion of pregnant individuals without justification denies them and their offspring access to potential health benefits, raising justice concerns considering growing data on DAA safety and global efforts to promote equitable and comprehensive HCV eradication. Finally, we propose a path forward for research and treatment programs during pregnancy to help advance the goal of HCV elimination.

Liver Transplantation Using Hepatitis C Virus-Viremic Donors Into Hepatitis C Virus-Aviremic Recipients as Standard of Care.

Liver transplantation (LT) using allografts from hepatitis C virus (HCV)‐viremic/nucleic acid testing–positive donors’ (DNAT+) organs into HCV‐aviremic recipients (rHCV−) has been limited owing to nearly universal HCV transmission and concerns regarding availability, safety, and efficacy post‐LT with direct‐acting antiviral (DAA) therapy. We report our experience of LT using DNAT+ organs into rHCV− as a routine standard of care. Following verification of DAA access, absence of critical drug‐drug interactions (DDIs) with DAAs, and informed consent, allocated DNAT+ organs were offered to patients on the waiting list for LT irrespective of recipient HCV status. Between June 2018 and December 2019, 292/339 rHCV− received an LT. Forty‐seven patients were excluded from analysis because of recipient HCV viremia, refusal to receive DNAT+ organs, or inability to receive DAA therapy post‐LT. Of these 292 patients, 61 rHCV− received DNAT+ livers (study group), and 231 rHCV− received DNAT− (aviremic donors [nuclear acid test‐negative donors]) livers (control group). Recipient and donor characteristics as well as 1‐year post‐LT patient and graft survival were similar between groups. In the study group, 4 patients died, and 1 patient required retransplantation within the first year post‐LT (all unrelated to HCV); 56 patients received DAA therapy, with a median time from LT to the start of DAA treatment of 66.9days (interquartile range [IQR], 36‐68.5), and 51 patients completed DAA treatment, all achieving sustained virologic response for 12 or more weeks (SVR‐12) (1 patient required retreatment owing to relapse following initial DAA therapy). No patients had evidence of fibrosing cholestatic hepatitis or extrahepatic manifestations of HCV. This report indicates that transplantation of DNAT+ livers into rHCV− and subsequent DAA therapy is associated with clinical outcomes comparable to those achieved with DNAT− allografts.

The impact of unrestricted access to direct-acting antiviral among incarcerated hepatitis C virus-infected patients.

Background/AimsDespite the disproportionally high prevalence rates of hepatitis C virus (HCV) amongst the incarcerated population, eradication remains challenging due to logistic and financial barriers. Although treatment prioritization based on disease severity is commonly practiced, the efficacy of such approach remained uncertain. We aimed to compare the impact of unrestricted access to direct-acting antiviral (DAA) among incarcerated HCV-infected patients in Singapore.MethodsIn this retrospective study, we reviewed all incarcerated HCV-infected patients treated in our hospital during the restricted DAA era (2013–2018) and unrestricted DAA access era (2019). Study outcomes included the rate of sustained virological response (SVR), treatment completion and treatment default. Subgroup analysis was performed based on the presence of liver cirrhosis, HCV genotype and HCV treatment types.ResultsA total of 1,001 HCV patients was followed-up for 1,489 person-year. They were predominantly male (93%) with genotype-3 HCV infection (71%), and 38% were cirrhotic. The overall SVR during the restricted DAA access era and unrestricted DAA access era were 92.1% and 99.1%, respectively. Unrestricted access to DAA exponentially improved the treatment access among HCV-infected patients by 460%, resulting in a higher SVR rate (99% vs. 92%, P=0.003), higher treatment completion rate (99% vs. 93%, P<0.001) and lower treatment default rate (1% vs. 9%, P<0.001).Conclusion: In this large cohort of incarcerated HCV-infected patients, we demonstrated that unrestricted access to DAA is an impactful strategy to allow rapid treatment up-scale in HCV micro-elimination.

HCV Micro-Elimination in HIV-Positive Individuals in the Netherlands: Three Years After Universal Access to Direct-Acting Antivirals

Background: In the Netherlands, access to direct-acting antivirals (DAA) against hepatitis C virus (HCV) infection has been unrestricted for chronic infection since 2015. We evaluated whether this changed the nationwide incidence of HCV primary and re-infection among HIV-positive individuals. Methods: Individuals participating in the national ATHENA HIV cohort between 2000-2018 were included. Incidence rates (IR) of HCV primary infection and re-infection were calculated per calendar year using piecewise exponential survival models. Findings: Among 22,775 individuals without prior HCV, 651 cases of HCV primary infection were documented (IR=2·9/1,000 person-years, 95%CI=2·7-3·1). The highest IR was observed in men who have sex with men (MSM) (4·5/1,000 person-years, 95%CI=4·1-4·8) and much lower among people who inject drugs (PWID) (0·8/1,000 person-years, 95%CI=0·4-1·6) and other transmission groups (0·2/1,000 person-years, 95%CI=0·1-0·4). In MSM, IR increased dramatically in 2007 (IR=8·3/1,000 person-years) and fluctuated between 4·6 and 8·6/1,000 person-years from 2008-2015. In 2016, IR declined to 2·6 cases/1,000 person-years and remained steady in 2017 and 2018 (IR=2·8 and 1·7/1,000 person-years, respectively). Among 1917 individuals with a previous HCV infection, 249 HCV re-infections were documented (IR=26·0/1,000 person-years, 95%CI=23·0-29·5). The highest IR was again observed in MSM (38·4/1,000 person-years, 95%CI=33·6-44·0) and was lower among PWID (5·5/1,000 person-years, 95%CI=2·1-14·6) and other transmission groups (9·5/1,000 person-years, 95%CI=6·7-13·5). In MSM, re-infection IRs fluctuated until 2015, reaching 51·4/1,000 person-years. In 2016, re-infection incidence declined to 37·0/1,000 person-years, followed by a further decrease in 2017 and 2018 (IR=25·1 and 15·1/1,000 person-years, respectively). Interpretation: The observed sharp decline in HCV incidence among HIV-positive MSM shortly after unrestricted DAA access suggests a “treatment-as-prevention” effect. HCV incidence was already low in PWID and other groups prior to unrestricted access. Ongoing HCV transmission is occurring in MSM, as illustrated by a declining but nonetheless high rate of reinfection, stressing the need for additional preventive measures. Funding: Dutch Ministry of Health, Welfare and Sport Conflict of Interest: BJAR reports grants from MSD and Gilead, all outside the submitted work; he hasparticipated in advisory boards organized by MSD, Gilead, Pfizer, ViiV Healthcare, Jansen Cilag, and Abbvie. EMM reports participating an advisory board of Gilead. WB reports other funds from GSK and non-financial support from Janssen, all outside the submitted work. KB reports participating in advisory boards of ViiV, Gilead, MSD and Janssen; he has received research grants form ViiV and Gilead. JS reports grants from Gilead Sciences, outside the submitted work. MP reports grants, personal fees and other funds from Gilead Sciences,Roche, MSD and Abbvie, all outside the submitted work. JA reports other funding fromGilead Sciences, Janssen-Cilag, Abbvie, BSM, and MSD, all outside the submitted work.MvdV reports grants and personal fees from Abbvie, Gilead, Johnson & Johnson, MSD, ViiV Healthcare, all outside the submitted work. All other authors report no conflicts of interest. PR reports grants from Gilead Sciences, ViiV Healthcare, and Merck & Co, and other funds from Gilead Sciences, ViiV Healthcare, Merck & Co, and Teva Pharmaceutical Industries, alloutside the submitted work. Ethical Approval: At its inception, the ATHENA cohort was approved by the institutional review boards of all participating centres. Individuals can opt out after being informed by their treating physician of the purpose of data and sample collection. Data are pseudonymized and made available to investigators in a coded form. Coded data may be used for scientific purposes without further consent. For the purpose of our analysis, only existing data have been used and therefore no additional review or consent was required.

Commentary on Barré et al. (2020): Identifying remaining barriers to hepatitis C treatment in the DAA era.

Untreated alcohol use disorder delays time to starting hepatitis C virus (HCV) treatment among people who inject drugs, even in the direct-acting anti-virals era. We need to identify and minimize remaining barriers to engaging in HCV care, including alcohol and other social factors. Significant increases in hepatitis C virus (HCV) treatment uptake have been observed since the introduction of broad access to direct-acting anti-viral (DAA) therapies in many countries 1. However, treatment uptake is now beginning to decline in some countries, and those not treated within the first years of DAA access may be more challenging to reach 2, 3. In the interferon era, HCV treatment uptake was extremely low; for example, estimates from France, Australia and Canada reported that 4, 2 and 1%, respectively, of those with hepatitis C viraemia were treated annually before 2014 4. Treatment uptake was particularly low among people who inject drugs (PWID), a key group at risk of HCV infection 5, 6. Substantial increases in treatment uptake among PWID since DAA availability have been reported in some contexts. For example, in Australia, treatment uptake among those participating in repeat cross-sectional studies at needle and syringe programmes increased from 10% in 2015 to 41% in 2017 7, and the incidence of HCV treatment initiation in a cohort of PWID in Montreal, Canada, increased from 1.6/100 person-years in 2011 to 12.7 in 2017 8. In this issue of Addiction, Barre and colleagues 9 found that treatment uptake in France among PWID who have a history of opioid substitution therapy (OST) remained similarly low in the interferon era (2012–13) and early DAA era (2014–15): treatment initiation among HCV-diagnosed PWID was approximately 6 per 100 person-years in both time-periods. Irrespective of treatment regimen, PWID with untreated alcohol use disorders were less likely to start HCV treatment than PWID living with chronic HCV without alcohol use disorders or on treatment for alcohol use disorder. That said, the magnitude of the reduced likelihood of treatment uptake among those with untreated alcohol use disorders appeared to be larger in the interferon era. These results are in the context of restricted access to DAA therapy in France until May 2016 10, when advanced liver disease was removed as a treatment criterion. Barre and colleagues approach involved analyzing untreated alcohol use disorder as a potential barrier to HCV treatment before and after DAA introduction, allowing comparison between these two time-periods. The resulting analysis provided insight into the probable reduction in the effect size of alcohol use disorder as a barrier to HCV treatment. At the same time it highlighted that, although the effect may have been attenuated, those with untreated alcohol use continue to be less likely to be treated for HCV in France than other PWID. The effect of untreated alcohol use disorder prior to and after the introduction of DAA could be compared even more directly, and this comparison could be quantified by considering DAA introduction as a potential effect modifier. The authors suggest that treatment of alcohol use disorders will improve access to therapy in this group. Whether or not that is the case, their analysis highlights the group with untreated alcohol use as a potential target for interventions aimed at improving linkage to care, and for qualitative research in order to identify potentially effective interventions. Barre and colleagues’ data, coupled with emerging evidence from the United States, Canada and Australia, reveal that barriers to treatment uptake persist in the DAA era. Treatment uptake has been associated with important social factors, other than alcohol use, including not being on OST, illicit drug use, unstable housing and geographic location of residence 7, 8, 11-14. These findings are sobering in an era of optimism that it will be possible to change HCV epidemiology by treating sufficient numbers of people with ongoing risk behaviours 15. In the DAA era, where treatment courses are short, all-oral, with minimal side-effects and adherence is far less important as a predictor of treatment outcomes 16, the provider-side rationale for reluctance to treat people who use alcohol and illicit drugs no longer applies but some barriers to treatment may persist nonetheless. Applying Barre and colleagues’ comparative approach to other potential remaining barriers to HCV treatment pre- and post- DAA introduction would provide insight into progress made since the introduction of DAAs, the remaining challenges and the potential targets for interventions to connect those remaining HCV infected with DAA treatment. A key point is that we all need to work better to educate prescribers to adopt a patient-centred approach to HCV treatment. Instead of waiting for PWID ‘to be ready’ for treatment, perhaps we should ask ourselves: ‘why are we not discussing treatment today’? This message continues to be relevant in the DAA era. R.S.-D. and D.K.v.S. have no conflicts to report. J.S.D. receives investigator-initiated research grants and honorarium from Gilead, Abbvie, Merck and Bristol Myers Squibb. The authors acknowledge the contribution to this work of the Victorian Operational Infrastructure Support Program received by the Burnet Institute. R.S.-D. and J.S.D. receive fellowship support from the Australian National Health and Medical Research Council.

Moving Towards Hepatitis C Microelimination Among People Living With Human Immunodeficiency Virus in Australia: The CEASE Study.

Microelimination of hepatitis C virus (HCV) among people living with human immunodeficiency virus (HIV) may be feasible in Australia, given unrestricted access to direct-acting antiviral (DAA) therapy from 2016. Our aim was to evaluate progress towards elimination goals within HIV/HCV-coinfected adults in Australia following universal DAA access. The CEASE prospective cohort study enrolled adults with HIV/HCV, irrespective of viremic status, from 14 primary and tertiary clinics in Australia. Annual and cumulative HCV treatment uptake, outcome, and HCV RNA prevalence were evaluated, with follow-up through May 2018 (median follow-up, 2.63 years). Factors associated with DAA uptake were analyzed. Between July 2014 and March 2017, 402 participants who were HIV/HCV antibody positive were enrolled (95% male [80% gay and bisexual men,], 13% cirrhosis, 80% history of injecting drug use [39% currently injecting]). Following universal DAA access, annual HCV treatment uptake in those eligible increased from 7% and 11% per year in 2014 and 2015, respectively, to 80% in 2016. By 2018, cumulative HCV treatment uptake in those ever eligible for treatment was 91% (336/371). HCV viremic prevalence declined from 82% (95% CI, 78-86%) in 2014 to 8% (95% CI, 6-12%) in 2018. Reinfection was reported in only 5 participants for a reinfection incidence of 0.81 per 100 person-years (95% CI, 0.34-1.94). High uptake and effectiveness of unrestricted DAA therapy in Australia have permitted rapid treatment scale-up, with a dramatic reduction in HCV infection burden and low reinfection rate among people living with HIV, suggesting that microelimination is feasible. NCT02102451.

The Effects of Hepatitis C Treatment Eligibility Criteria on All-cause Mortality Among People With Human Immunodeficiency Virus.

The cost of direct-acting antivirals (DAAs) for hepatitis C virus (HCV) prompted many payers to restrict treatment to patients who met non-evidence-based criteria. These restrictions have implications for survival of people with HCV, especially for people with human immunodeficiency virus (HIV)/HCV coinfection who are at high risk for liver disease progression. The goal of this work was to estimate the effects of DAA access policies on 10-year all-cause mortality among people with HIV. The study population included 3056 adults with HIV in the Women's Interagency HIV Study and Multicenter AIDS Cohort Study from 1 October 1994 through 30 September 2015. We used the parametric g-formula to estimate 10-year all-cause mortality under DAA access policies that included treating (i) all people with HCV; (ii) only people with suppressed HIV; (iii) only people with severe fibrosis; and (iv) only people with HIV suppression and severe fibrosis. The 10-year risk difference of treating all coinfected persons with DAAs compared with no treatment was -3.7% (95% confidence interval [CI], -9.1% to .6%). Treating only those with suppressed HIV and severe fibrosis yielded a risk difference of -1.1% (95% CI, -2.8% to .6%), with 51% (95% CI, 38%-59%) of coinfected persons receiving DAAs. Treating a random selection of 51% of coinfected persons at baseline decreased the risk by 1.9% (95% CI, -4.7% to .3%). Restrictive DAA access policies may decrease survival compared to treating similar proportions of people with HIV/HCV coinfection with DAAs at random. These findings suggest that lives could be saved by thoughtfully revising access policies.

Economic Consequences of Investing in Anti-HCV Antiviral Treatment from the Italian NHS Perspective: A Real-World-Based Analysis of PITER Data.

We estimated the cost consequence of Italian National Health System (NHS) investment in direct-acting antiviral (DAA) therapy according to hepatitis C virus (HCV) treatment access policies in Italy. A multistate, 20-year time horizon Markov model of HCV liver disease progression was developed. Fibrosis stage, age and genotype distributions were derived from the Italian Platform for the Study of Viral Hepatitis Therapies (PITER) cohort. The treatment efficacy, disease progression probabilities and direct costs in each health state were obtained from the literature. The break-even point in time (BPT) was defined as the period of time required for the cumulative costs saved to recover the Italian NHS investment in DAA treatment. Three different PITER enrolment periods, which covered the full DAA access evolution in Italy, were considered. The disease stages of 2657 patients who consecutively underwent DAA therapy from January 2015 to December 2017 at 30 PITER clinical centres were standardized for 1000 patients. The investment in DAAs was considered to equal €25 million, €15 million, and €9 million in 2015, 2016, and 2017, respectively. For patients treated in 2015, the BPT was not achieved, because of the disease severity of the treated patients and high DAA prices. For 2016 and 2017, the estimated BPTs were 6.6 and 6.2years, respectively. The total cost savings after 20years were €50.13 and €55.50 million for 1000 patients treated in 2016 and 2017, respectively. This study may be a useful tool for public decision makers to understand how HCV clinical and epidemiological profiles influence the economic burden of HCV.

Hepatitis C in Lebanon: burden of the disease and value of comprehensive screening and treatment.

As few reliable data on the burden of hepatitis C virus (HCV) are available from the Middle East, we analyzed HCV burden in the Lebanese population and the value of comprehensive screening and treatment at different age groups and fibrosis stages. A multi-cohort, health-state-transition model was developed to project the number of HCV patients achieving a sustained virologic response 12 weeks after treatment (SVR12) or progressing to compensated cirrhosis (CC), decompensated cirrhosis (DCC), hepatocellular carcinoma (HCC), and liver-related death (LrD) from 2016 to 2036. Epidemiology and mortality data were extracted from the Ministry of Health bulletin while costs were collected from insurance claims. The proportion of patients screened for HCV was projected to increase to 60%/85%/99% (low/medium/high screening scenarios) in 2036, with a new cohort being diagnosed each year. SVR12 rates were extracted from clinical trials. Separate models were used for 18-39 and 40- 80 age groups to account for different prevalence and screening rates. Low, medium and high HCV screening scenarios showed that 3,838, 5,665 and 7,669 individuals would be diagnosed with HCV infection from 2016 to 2036, 40% aged 18-39 and 60% aged 40-80. In the absence of treatment, the projected number of patients reaching CC, DCC, HCC and LrD in 2036 was 899, 147, 131 and 147 respectively for the 18-39 age groups. In the 40-80 age groups, these projections were substantially greater: 2,828 CC, 736 DCC, 668 HCC and 958 LrD. The overall economic burden of these complications would reach 150 million €. However, introducing direct-acting antivirals (DAAs) for F0-F4 patients would increase by 43% and 62% the proportion of remaining life-years (LYs) spent in SVR12 compared to DAAs given to F2-F4 or to F3-F4 only, respectively. Although DAAs for F0-F4 increase the cost of HCV treatment, they also provide the greatest health benefit and lowest cost per LY gained in SVR12. Compared to no treatment and screening, adopting the high screening variant and DAAs access to F0-F4 would cost an additional 1,957 € for every LY gained in SVR12 for patients aged 18-39 and -168 € for the 40-80 age group. An enhanced screening policy coupled with broader access to DAAs will diminish the future burden of HCV in the Lebanese population and provide the greatest health benefits among middle-aged and elder adults with net cost savings.

Prioritization for interferon-free regimens and potential drug interactions of current direct-acting anti-hepatitis C agents in routine clinical practice.

BackgroundWe determined the proportions of patients with chronic hepatitis C (CHC) in association with possible prioritized indications for interferon-free regimens and the use of co-medications with potential drug-drug interactions (DDIs).MethodsFive hundred consecutive mono-infected CHC patients seen in 2015 at 5 Greek centers were included. Priorities for interferon-free regimens were based on liver disease severity, contraindication(s) for interferon and prior interferon-treatment failure. All co-medications were classified into those with no DDIs/no clear data for DDIs, potential DDIs, and contraindication due to DDI for each agent, according to the HEP Drug Interaction Checker.ResultsOf the 500 patients, 1% had undergone liver transplantation, whereas 6.6% had decompensated cirrhosis, 21.8% F4, 17.1% F3, 10.4% F2, and 34.8% F0-1 fibrosis. Contraindications for interferon were present in 38.5% of non-transplant patients with compensated liver disease. The probability of contraindications/potential DDIs was greater for boceprevir/telaprevir and ombitasvir/paritaprevir/ritonavir±dasabuvir, compared to all other agents (P<0.001), and least for sofosbuvir (P<0.05). Contraindications/potential DDIs were more frequently present in patients ≥50 than <50 years old (P≤0.034), and more common in F3-4 than F0-2, and F4 than F0-3 fibrosis (P≤0.019) for all direct-acting antivirals (DAAs).ConclusionsThe expansion of the criteria for prioritization of interferon-free regimens from cirrhosis to F3 and perhaps F2 fibrosis will increase the proportion of patients with DAA access by only 10-15% and 10%, respectively. A potential for DDIs is frequently present with protease inhibitors, but also exists with other DAAs. The probability of DDIs is higher in patients with priority for DAAs, including those who have advanced liver disease and are usually of older age.

Disparities in HIV clinic care across Europe: findings from the EuroSIDA clinic survey.

BackgroundAlthough advances in HIV medicine have yielded increasingly better treatment outcomes in recent years, HIV-positive people with access to antiretroviral therapy (ART) still face complex health challenges. The EuroSIDA Study Group surveyed its clinics to explore regional differences in clinic services.MethodsThe EuroSIDA study is a prospective observational cohort study that began enrolling patients in 1994. In early 2014, we conducted a 59-item survey of the 98 then-active EuroSIDA clinics. The survey covered HIV clinical care and other aspects of patient care. The EuroSIDA East Europe study region (Belarus, Estonia, Lithuania, the Russian Federation and Ukraine) was compared to a “non-East Europe” study region comprised of all other EuroSIDA countries.ResultsA larger proportion of clinics in the East Europe group reported deferring ART in asymptomatic patients until the CD4 cell count dropped below 350 cells/mm3 (75 % versus 25 %, p = 0.0032). Considerably smaller proportions of East Europe clinics reported that resistance testing was provided before ART initiation (17 % versus 86 %, p < 0.0001) and that it was provided upon treatment failure (58 % versus 90 %, p = 0.0040). Only 33 % of East Europe clinics reported providing hepatitis B vaccination, compared to 88 % of other clinics (p < 0.0001). Only 50 % of East Europe clinics reported having access to direct-acting antivirals for hepatitis C treatment, compared to 89 % of other clinics (p = 0.0036). There was significantly less tuberculosis/HIV treatment integration in the East Europe group (27 % versus 84 % p < 0.0001) as well as significantly less screening for cardiovascular disease (58 % versus 90 %, p = 0.014); tobacco use (50 % versus 93 %, p < 0.0001); alcohol consumption (50 % versus 93 %, p < 0.0001); and drug use (58 % versus 87 %, p = 0.029).ConclusionsStudy findings demonstrate how specific features of HIV clinics differ across Europe. Significantly more East Europe clinics deferred ART in asymptomatic patients for longer, and significantly fewer East Europe clinics provided resistance testing before initiating ART or upon ART failure. The East Europe group of clinics also differed in regard to hepatitis B vaccination, direct-acting antiviral access, tuberculosis/HIV treatment integration and screening for other health issues. There is a need for further research to guide setting-specific decision-making regarding the optimal array of services at HIV clinics in Europe and worldwide.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-016-1685-x) contains supplementary material, which is available to authorized users.