Lynn E. Taylor

Restrictions for Medicaid Reimbursement of Sofosbuvir for the Treatment of Hepatitis C Virus Infection in the United States

Highly effective (cure rate >90%), once-daily, oral interferon-free treatments with minimal adverse effects are now available for hepatitis C virus (HCV) infection. Worldwide, an estimated 80 to 150 million persons have chronic HCV (1, 2). If left untreated, chronic HCV can lead to cirrhosis, liver failure, and hepatocellular carcinoma (HCC) (3, 4). Rates of advanced liver disease complications, associated health care costs, and liver diseaserelated mortality are rising worldwide (3, 4). Regimens for treating HCV seem to be curative and reduce liver-related and all-cause mortality (5). Uptake of HCV treatment has been low in many settings (68) in part because of the poor tolerability of interferon-based regimens. Widespread access to interferon-free regimens has the potential to greatly affect HCV morbidity and mortality. Sofosbuvir, a pan-genotypic nucleotide analogue NS5B polymerase inhibitor indicated for treatment of chronic HCV in combination with other direct-acting antivirals (DAAs), was approved by the U.S. Food and Drug Administration (FDA) on 6 December 2013. Sofosbuvir is the first DAA indicated for use as part of an interferon-free regimen. Compared with interferon-based therapy, sofosbuvir-based interferon-free regimens show response rates greater than 90%, shortened treatment duration (8 to 12 weeks), and improved tolerability and safety (although with some combinations, lower responses are seen in persons with more advanced disease and certain HCV genotypes) (914). The wholesale acquisition cost of sofosbuvir is

Hepatic Steatosis Is Associated with Fibrosis, Nucleoside Analogue Use, and Hepatitis C Virus Genotype 3 Infection in HIV-Seropositive Patients

1000 per day (equating to

Recommendations for the management of hepatitis C virus infection among people who inject drugs

84000 for a 12-week course) and must be used with 1 or more medications at additional cost. A fixed-dose, single-tablet combination of sofosbuvir and ledipasvir (an NS5A inhibitor) is now available at a wholesale acquisition cost of

HIV Coinfection With Hepatitis C Virus: Evolving Epidemiology and Treatment Paradigms

1125 per day (

Recommendations for the Management of Hepatitis C Virus Infection Among People Who Inject Drugs

63000,

Breaking Down the Barriers to Hepatitis C Virus (HCV) Treatment Among Individuals With HCV/HIV Coinfection: Action Required at the System, Provider, and Patient Levels

94500, and

HIV Mono-infection Is Associated With FIB-4 – A Noninvasive Index of Liver Fibrosis – in Women

189000 for an 8-, 12-, and 24-week course, respectively). The high price of these regimens and high demand (actual or anticipated) for them has led payers to restrict access, although by law Medicaid programs are entitled to a rebate of at least 23% (15, 16). Some payers have negotiated ample rebates; however, they have not altered their reimbursement restrictions. Further complicating matters is that different federal standards apply depending on whether a beneficiary is eligible under traditional Medicaid or is newly eligible for Medicaid in 1 of the 28 states that have implemented the Patient Protection and Affordable Care Act Medicaid expansion provision (16). Within the 51 fee-for-service Medicaid programs, there are also different programs and requirements for different populations and different models of care financing and delivery (for example, fee-for-service and managed care organizations). For the purposes of this article, we have focused on state fee-for-service programs and not managed care. Because our focus here is on clinical factors, detailed legal analysis of the many complex Medicaid program rules is beyond the scope of this article. In the United States, a disproportionate number of persons living with HCV have low income (17). For purposes of this article, low income means having income at or below the highest state Medicaid eligibility limit for parents of dependent children. Currently, the state with the highest Medicaid income eligibility limit is Connecticut at 201% of the federal poverty level. Further, the 2015 federal poverty level for a single person in all states except Alaska and Hawaii is

Incident Hepatitis C Virus Infection among US HIV-Infected Men Enrolled in Clinical Trials

11770; 201% equals

Delivering Care to Injection Drug Users Coinfected with HIV and Hepatitis C Virus

23658 (18). Most persons are eligible for reimbursement of HCV therapy through Medicaid, which is the jointly funded federal and state partnership that provides health insurance for low-income persons meeting the programs eligibility criteria. Each state has wide discretion in administering its own Medicaid program. Although this creates unique Medicaid programs in each state, states must follow some federal standards (16). These include covering all FDA-approved drugs, consistent with FDA labeling, whose manufacturers participate in Medicaids prescription drug rebate program (19), and not discriminating in drug coveragethus a state may not arbitrarily deny or reduce the amount, duration, or scope of a required service to an otherwise eligible beneficiary solely because of the diagnosis, type of illness, or condition (20). In 2014, the American Association for the Study of Liver Disease and the Infectious Diseases Society of America (AASLD/IDSA) issued recommendations (21) for testing, managing, and treating HCV (which are updated regularly). Little is known about the consistency in applying these guidelines by state Medicaid committees to reimbursement criteria for sofosbuvir. The aim of this study was to systematically evaluate state Medicaid policies for the reimbursement of sofosbuvir for HCV treatment in the United States. Methods We evaluated Medicaid reimbursement criteria for sofosbuvir for all 50 states and the District of Columbia. We searched state Medicaid Web sites between 23 June and 7 December 2014. Locating criteria for coverage was difficult. Each state has different means of organizing Medicaid information online, no consistent word search was able to locate each policy, and each state required a different process to find the appropriate policies or forms. As such, this search was confined to online information. When state policy was unclear, and when states did not operate a fee-for-service pharmacy program, we indicated that the state criteria and policies were unknown. Only states with fee-for-service programs were included. Data were extracted by 2 coauthors in duplicate and entered into a standardized spreadsheet; 2 different coauthors crosschecked the extracted data. Any differences were resolved by consensus. Each entry was double-checked by another coauthor to ascertain accuracy. For each state, the following data were extracted from Medicaid reimbursement criteria: whether sofosbuvir was covered (paid for by Medicaid) and the criteria for coverage. Most Medicaid programs require preapproval of certain medications before a patient may receive them, and providers must complete this prior authorization. For each state, Medicaid prior authorization criteria for sofosbuvir were also extracted, where available. The date of the state Medicaid reimbursement publication and uniform resource locators of the prior authorization and the preferred drug list were recorded and entered into a database (Excel, version 14.4.4 [Microsoft]). Criteria for sofosbuvir coverage based on the following categories were recorded: liver disease stage, HIV co-infection, prescriber type, and drug or alcohol use. For criteria about liver disease staging, data were collected on the level of fibrosis required for reimbursement (either none indicated, Meta-Analysis of Histologic Data in Viral Hepatitis [METAVIR] fibrosis stage F2 or higher, or F3 or F4), eligibility for persons with decompensated cirrhosis, and whether a liver biopsy was mandatory to provide evidence of advanced fibrosis. For criteria about HIV co-infection, data were collected on whether HIV status needed to be documented, and if positive, whether the patient had to be receiving antiretroviral therapy (ART) or have suppressed HIV RNA levels. For prescriber type, data were collected on whether the prescriber had to be a specialist (gastroenterology, hepatology, infectious diseases, or liver transplantation) or whether treatment decisions needed to be made in consultation with a specialist. For criteria about drug or alcohol use, data were collected on whether there were any substance-related access criteria, and if so, whether drug or alcohol counseling was required, whether patients had to be evaluated for drug and/or alcohol dependence, whether a period of abstinence was required (1, 3, 6, or 12 months) before sofosbuvir therapy, and whether drug or alcohol testing and/or treatment was required before sofosbuvir therapy. Results Overall, 42 states (82%), including the District of Columbia, had publicly available information about Medicaid reimbursement criteria for sofosbuvir (Tables 1 and 2 and Figures 1 and 2). Nevada is the only state that does not require prior authorization for sofosbuvir. Nine states have unknown criteria, with neither the prior authorization nor eligibility information publicly available. Table 1. State Eligibility/Ineligibility Criteria for Sofosbuvir Approval Table 2. State Substance UseRelated Requirements for Sofosbuvir Approval Figure 1. Medicaid reimbursement criteria for sofosbuvir based on documented liver fibrosis stage required for reimbursement. METAVIR = Meta-Analysis of Histologic Data in Viral Hepatitis. Figure 2. Medicaid reimbursement criteria for sofosbuvir based on the required period of abstinence from drug and alcohol use. Of the 42 states, including the District of Columbia, with known Medicaid reimbursement criteria for sofosbuvir, 81% (n= 34) restrict reimbursement on the basis of liver disease stage (Table 1). In 4 states (10%), reimbursement is restricted only to persons with cirrhosis (F4). In two thirds of states (n= 27), sofosbuvir reimbursement is restricted to persons with advanced fibrosis (F3) or cirrhosis (F4). In 2 states (5%), reimbursement is also provided for those with moderate fibrosis (F2) and in 1 state for mild fibrosis (F1). In the remaining states, no reimbursement criteria are based on disease stage (n= 8 [19%]). Sofosbuvir use is restricted in persons with decompensated cirrhosis in 7 states (17%). Colorado is the only state that explicitly includes persons with decompensated cirrhosis. Liver biopsy staging is required for demonstrating cirrhosis in 5 states (12%), although Arkansas also requires liver biopsy for evidence of bridging fibrosis (F3). In Tennessee, liver biopsy or transient elastography are the only options allowed to demonstrate cirrhosis. Nineteen states (45%) require information about HIV status. Ten (24%) requ

Management of Hepatitis C Virus/HIV Coinfection Among People Who Use Drugs in the Era of Direct-Acting Antiviral–Based Therapy

BACKGROUND We conducted a study to determine the prevalence and factors associated with hepatic steatosis in human immunodeficiency virus (HIV)-seropositive patients with hepatitis C and to investigate whether steatosis is associated with liver fibrosis. METHODS Retrospective chart reviews were conducted in 4 hospitals that serve community-based and incarcerated HIV-infected patients who had undergone a liver biopsy for evaluation of hepatitis C virus (HCV) infection during the period of 2000-2003. Demographic characteristics and medication and laboratory data were collected from the time of the biopsy. A pathologist blinded to all clinical data evaluated the specimens. The primary outcome was presence or absence of steatosis. RESULTS Of 260 HIV-HCV-coinfected patients, 183 met inclusion criteria and had a biopsy specimen adequate for review. Steatosis was present in 69% of patients (graded as minimal in 31%, mild in 27%, moderate in 18%, and severe in 1%). Factors associated with steatosis included use of dideoxynucleoside analogues, such as didanosine and stavudine (odds ratio [OR], 4.63; 95% confidence interval [CI], 1.55-13.82). There was a trend toward presence of steatosis and use of other nucleoside analogues or infection with HCV genotype 3 (OR, 2.65 [95% CI, 0.95-7.41] and 3.38 [95% CI, 0.86-13.28], respectively). The presence of steatosis was associated with fibrosis (OR, 1.37; 95% CI, 1.03-1.81). CONCLUSIONS In this multiracial population of HIV-HCV-coinfected patients, steatosis was prevalent and was associated with severity of liver fibrosis. Use of nucleoside analogues (particularly didanosine and stavudine) and HCV genotype 3 infection were associated with hepatic steatosis. The development of steatosis is multifactorial in nature and may play a contributory role in the progression of liver disease in HIV-infected patients.