Treatment of Chronic Hepatitis C Virus Infection in Adults

April 17, 2023

Purpose of This Guideline

Date of current publication: April 17, 2023
Lead author: David E. Bernstein, MD
Writing group: Joshua S. Aron, MD; Christine A. Kerr, MD; Colleen Flanigan, RN, MS; Christopher J. Hoffmann, MD, MPH; Charles J. Gonzalez, MD
Committee: Hepatitis C Virus (HCV) Guideline Committee
Date of original publication: July 31, 2017

This guideline for treatment of chronic hepatitis C virus (HCV) infection was developed by the New York State Department of Health AIDS Institute (NYSDOH AI) to guide primary care providers and other practitioners in New York State in treating patients with chronic HCV infection. The guideline aims to achieve the following goals:

  • Provide clinicians with current clinical evidence-based recommendations on treating and curing chronic HCV to 1) increase the number of New York State residents treated for and cured of chronic HCV and 2) reduce the growing burden of morbidity and mortality associated with chronic HCV infection.
  • Educate clinicians on safely and correctly prescribing anti-HCV medications.
  • Educate clinicians on the effects of HCV infection during pregnancy and the risk of vertical HCV transmission during the perinatal period.
  • Advise clinicians on the risks associated with HCV treatment in pregnant individuals.
  • Provide evidence-based clinical recommendations to support the goals of the New York State Hepatitis C Elimination Plan (NY Cures HepC).

Treatment and cure of chronic HCV: The availability of safe and effective regimens of oral direct-acting antivirals (DAAs) revolutionized HCV care, and DAA regimens are the standard of care for treating and curing chronic HCV. DAAs are molecules that work at different stages of the HCV lifecycle, targeting and inhibiting specific nonstructural proteins of HCV to disrupt viral replication and infection UpToDate 2021. The classes of DAAs are defined by their mechanism of action and therapeutic target.

Current DAAs for treatment of chronic HCV:

  • Protease inhibitors (-previrs): glecaprevir, voxilaprevir, grazoprevir
  • NS5A inhibitors (-asvirs): ledipasvir, velpatasvir, pibrentasvir, elbasvir
  • NS5B nucleoside polymerase inhibitor (-buvir): sofosbuvir

The goal of HCV therapy is a sustained virologic response (SVR), which is defined as the absence of detectable HCV RNA at least 12 weeks after treatment completion. An SVR is the equivalent of a cure. DAA regimens have been associated with an SVR rate of ≥90% and have excellent tolerability in both treatment-naive and treatment-experienced patients with and without cirrhosis Falade-Nwulia, et al. 2017.

See the tables in the guideline section Recommended DAA Treatment Regimens for options for initial treatment of chronic HCV or retreatment of chronic HCV after treatment failure.

HCV Treatment Goals and Considerations

RECOMMENDATIONS

Considerations in HCV Treatment

  • Before initiating antiviral therapy, clinicians should assess CrCl, HIV and HBV status, and the degree of fibrosis, among other factors. (A1)
  • Clinicians new to HCV treatment should consult a specialist in treatment of liver disease or viral hepatitis when treating patients who:
    • Have severe renal impairment (CrCl <30 mL/min) and/or are undergoing hemodialysis. (A3)
    • Require retreatment after treatment failure of any DAA regimen. (B3)
  • Clinicians should prescribe RBV with caution for patients with a CrCl <50 mL/min. (A1)
    • If prescribed, a reduced dose of 200 mg per day is required.
    • Non-RBV-containing regimens can be prescribed without dose adjustments for patients with CrCl ≥30 mL/min.
Contraindications
  • Clinicians should not prescribe RBV for treatment of the following patients:
    • Female or male patients planning conception within 6 months of the last dose of RBV. (A2)
    • Male patients who have pregnant partners. (A2)

Abbreviations: CrCl, creatinine clearance; DAA, direct-acting antiviral; HBV, hepatitis B virus; HCV, hepatitis C virus; RBV, ribavirin.

Goals

The goal of treatment in patients with chronic HCV infection is to attain a virologic cure, as evidenced by a sustained viral response, in order to reduce all-cause mortality and liver-related complications, including end-stage liver disease, hepatocellular carcinoma, and the morbidity and mortality associated with the extrahepatic manifestation of chronic HCV infection. With the significant advances in treatment, all patients with chronic HCV infection, regardless of fibrosis stage, are considered candidates for antiviral therapy Simmons, et al. 2015Smith-Palmer, et al. 2015van der Meer, et al. 2012.

KEY POINTS
  • Clinicians can increase their patients’ ability to understand treatment-related information and participate in decision-making if they communicate with clear, easily understood, jargon-free, and culturally sensitive language.
  • Patient preferences are central to all treatment decisions.

Considerations

This guideline includes recommendations for treating patients with chronic HCV infection, with consideration of individual characteristics such as viral genotype, presence of cirrhosis, and previous treatment history. Concurrent medical conditions, potential drug-drug interactions, and cost/coverage influence are factors in selecting HCV treatment regimens; sex, age, viral load levels, substance use disorders, mental health disorders, and HIV coinfection are not factors in choosing regimens.

The tables in the guideline section Recommended DAA Treatment Regimens present several options for treatment in each category. No regimen is prioritized or recommended over another; regimens are listed alphabetically.

KEY POINT
  • Cardiac disease and other comorbidities may affect a patient’s ability to tolerate RBV-induced anemia and should be considered before initiating an RBV-containing regimen.

Renal impairment: For patients with a CrCl <50 mL/min, RBV should be used with caution; if used, a reduced dose of 200 mg per day is recommended FDA 2011. No dose adjustment of ledipasvir/sofosbuvir, sofosbuvir/velpatasvir, sofosbuvir/velpatasvir/voxilaprevir, or glecaprevir/pibrentasvir is required in patients with mild, moderate, or severe renal impairment FDA(a) 2019FDA(b) 2019FDA 2017FDA(a) 2016.

Resistance testing: At present, testing for resistance-associated substitutions (RASs) is not universally recommended. RASs are also referred to as resistance analysis populations and resistance-associated variants. RAS testing is performed when retreatment is considered for patients for whom treatment with a DAA regimen containing an NS5A or NS5B inhibitor has failed (see guideline section Recommended DAA Regimens After PEG-IFN Treatment Failure).

NS5A testing is recommended in patients with HCV genotype 3 who are being considered for 12 weeks of sofosbuvir/velpatasvir and are treatment-naive and have cirrhosis or are treatment-experienced Hezode, et al. 2018Foster, et al. 2015. If the Y93H RAS is present, weight-based RBV should be added to the regimen or another regimen should be selected.

For more information on HCV resistance, see the Infectious Diseases Society of America/American Association for the Study of Liver Disease HCV Resistance Primer.

HCV Testing and Management in Pregnant Adults

RECOMMENDATIONS
HCV Testing and Management in Pregnant Adults
  • Clinicians should perform HCV testing in all patients who are planning to get pregnant (A2) or are currently pregnant (B3), and screening should be repeated with each pregnancy (B3).
  • Clinicians should advise pregnant patients diagnosed with chronic HCV (a positive HCV antibody test result and detectable HCV RNA) to defer treatment with DAAs until they are no longer pregnant or breastfeeding. (A2)
  • If an individual with HCV becomes pregnant during DAA treatment, the clinician should:
    • Advise that the use of DAAs is not currently recommended during pregnancy because of insufficient safety data on the effect on the fetus.
    • Discuss the risks and benefits of continuing treatment.
  • Clinicians should refer pregnant patients diagnosed with HCV to a specialist experienced in managing HCV in pregnancy, e.g., hepatologist, gastroenterologist, infectious disease specialist, or high-risk obstetrician. (A3)
  • If a pregnant patient with HCV has a substance use disorder, the clinician should provide or refer the patient for substance use treatment, including harm reduction services. (A3)
  • Clinicians should advise pregnant and postpartum individuals with HCV monoinfection that HCV is not transmitted through breast milk and breastfeeding is considered safe. (B3)
  • Clinicians should advise patients to discontinue breastfeeding if they have or develop cracked or bleeding nipples and to express and discard milk until the bleeding has resolved. (B3)
  • Clinicians should refer infants born to mothers with HCV to pediatricians with experience in HCV care. (A3)
Contraceptive Use With HCV Treatment Containing RBV
  • Before initiating RBV as part of an HCV treatment regimen in a patient of childbearing potential, clinicians should confirm a negative pregnancy test and advise patients to use 2 methods of birth control for the duration of DAA therapy and 6 months after completion. (A2)
  • If a patient becomes pregnant while taking RBV, the clinician should discontinue the RBV. (A1)
  • Contraindication: Clinicians should not prescribe RBV for any patient planning pregnancy within 6 months of the last RBV dose or any male patient with a pregnant partner. (A2)

Abbreviations: AASLD, American Association for the Study of Liver Diseases; CDC, Centers for Disease Control and Prevention; DAA, direct-acting antiviral; HCV, hepatitis C virus; IDSA, Infectious Diseases Society of America; RBV, ribavirin.

HCV screening during pregnancy: In New York State, excluding New York City, 2,416 cases of HCV were reported in 2020 among individuals of childbearing age, 15 to 44 years old NYSDOH 2022. In New York City, in 2020, 447 cases of HCV were reported among individuals of childbearing age NYCDOHMH 2021.

These data raise concerns about reaching and treating this population and the potential for perinatal HCV transmission. Data indicate that in areas of high HCV prevalence, 10% to 28% of pregnant individuals with HCV infection are not identified through risk-based screening Andes, et al. 2021Koniares, et al. 2020Fernandez, et al. 2016Waruingi, et al. 2015Thomas 2013. Thus, in alignment with Centers for Disease Control and Prevention Schillie, et al. 2020 and American College of Obstetricians and Gynecologists (ACOG) ACOG 2022 recommendations, the NYSDOH and this committee recommend universal testing for HCV infection in individuals who are pregnant or planning to become pregnant and that screening be repeated with each pregnancy. Identifying HCV presents an opportunity to ensure linkage to care and guide obstetric clinicians on the maternal and fetal risks in pregnant patients with HCV. In addition, universal HCV testing during pregnancy appears to be cost-effective Chaillon, et al. 2021Tasillo, et al. 2019.

KEY POINTS
  • All pregnant individuals should be tested for HCV during each pregnancy, along with hepatitis B virus and other suggested prenatal tests.
  • If patients engage in ongoing high-risk behaviors during pregnancy, rescreening during pregnancy or the postpartum period is appropriate.

HCV infection during pregnancy: There are no published large-scale studies on DAA treatment for HCV during pregnancy, and treatment of pregnant individuals is not currently recommended. Clinical trials are underway to evaluate the use of DAAs for the treatment of HCV during pregnancy Chappell, et al. 2020Yattoo 2018, and the clinician could discuss the possibility of clinical trial participation and refer the patient as appropriate (see Clinical Trials.gov).

If an individual becomes pregnant during DAA treatment, the clinician and patient should discuss the risks (e.g., no information on the effects of the medication on the fetus) and benefits (e.g., probable HCV cure) of continuing treatment and refer the patient to a specialist experienced in managing HCV in pregnancy, such as a hepatologist, gastroenterologist, infectious disease specialist, or high-risk obstetrician. Clinicians with patients who have been exposed to DAA treatment during pregnancy can contact the Treatment in Pregnancy for Hepatitis C Registry.

HCV infection, compared with no HCV infection, is associated with a higher incidence of intrahepatic cholestasis in pregnancy. Intrahepatic cholestasis in pregnancy has significant maternal and fetal morbidity Wijarnpreecha, et al. 2017, and patients with HCV and this condition should be followed by a liver specialist or an obstetrician experienced in managing high-risk pregnancies Wijarnpreecha, et al. 2017. HCV infection during pregnancy has been associated with other adverse maternal and fetal outcomes, including gestational diabetes, low birth weight, small for gestational age, impaired intrauterine fetal growth, preterm delivery, miscarriage, and congenital anomalies Connell et al. 2011. Researchers note that the specific role of HCV in determining these outcomes is unclear because the data may be confounded by comorbid polysubstance use Connell, et al. 2011. Patients with HCV and recent or active substance use during pregnancy should be referred to care providers experienced in managing substance use during pregnancy for evaluation, treatment, and harm reduction services.

Perinatal transmission: Approximately 1.0% to 3.6% of pregnant individuals in the United States have HCV infection Edlin, et al. 2015Floreani 2013, and the risk of perinatal transmission is estimated at 6% for patients with HCV monoinfection and >10% for patients with HIV/HCV coinfection Pawlowska 2015Arshad, et al. 2011. Currently, no antiviral treatment is available to reduce HCV transmission during pregnancy.

Intrauterine, intrapartum, and postpartum HCV transmission to the fetus have been reported, but postpartum transmission is believed to be rare Gibb, et al. 2000. In utero transmission may occur during all 3 trimesters, and the risk of transmission may be associated with high maternal HCV RNA levels Elrazek, et al. 2017. When an individual’s immune response is altered during pregnancy, HCV RNA levels usually increase during the second and third trimesters, and there is a synchronous decrease in maternal alanine transaminase levels Gervais, et al. 2000. HCV RNA levels decline after delivery; spontaneous postpartum clearance of the HCV infection has been reported and should be considered when evaluating postpartum patients for treatment Hashem, et al. 2017Prasad and Honegger 2013.

Data are limited on intrauterine HCV transmission during invasive procedures, such as fetal scalp monitoring, intrauterine pressures, chorionic villi sampling, and amniocentesis. Conditions such as premature rupture of membranes during pregnancy have been associated with increased risk of HCV transmission Mast, et al. 2005. However, observational studies have demonstrated that mode of delivery (Cesarean section [C-section] or vaginal) is not associated with the rate of perinatal HCV transmission Ghamar Chehreh, et al. 2011Mast, et al. 2005European Paediatric Hepatitis C Virus Network 2001. The Society for Maternal-Fetal Medicine/ACOG guidelines recommend against performing a C-section simply to reduce the risk of HCV transmission Hughes, et al. 2017Cottrell, et al. 2013.

Breastfeeding: For postpartum individuals with HCV, breastfeeding is an option and is not associated with an increased risk of HCV transmission to the infant Cottrell et al. 2013. However, it should be noted that if the postpartum individual has cracked or bleeding nipples, HCV transmission may occur during breastfeeding through blood or nonintact skin exposure CDC 2021. Early discussion with lactation consultants during or after pregnancy may be helpful to minimize difficulties with breastfeeding. For pregnant patients with HIV/HCV coinfection, clinicians should consult ACOG: Labor and Delivery Management of Women With Human Immunodeficiency Virus Infection.

Contraceptive use with HCV treatment containing RBV: For all female and male patients planning conception within 6 months of treatment, use of RBV is contraindicated due to the teratogenic effects of the drug Sinclair, et al. 2017FDA 2011. Before prescribing an RBV-containing regimen for a patient of childbearing potential, a negative pregnancy test is required immediately before initiation of therapy, and using 2 forms of contraception or abstinence is advised during therapy and for 6 months after. Extreme care must be taken to avoid pregnancy during therapy and for 6 months after completion of therapy in female patients and female partners of male patients taking RBV.

If an individual with HCV becomes pregnant while taking an HCV treatment regimen containing RBV, RBV should be discontinued.

Recommended DAA Treatment Regimens

RECOMMENDATIONS

Abbreviations: DAA, direct-acting antiviral; HCV, hepatitis C virus; PEG-IFN, pegylated interferon; RAS, resistance-associated substitution; RBV, ribavirin.

All regimens listed in this guideline were available as of October 2022.

These recommendations for treatment of chronic HCV in adults ≥18 years old were developed by the NYSDOH AI HCV Guideline Committee to guide primary care providers and other clinicians in New York State in treating patients with chronic HCV infection. Treatment guidelines for patients ≤17 years old are available at the American Association of the Study of Liver Diseases/Infectious Disease Society of America HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C. All available DAA regimens are pangenotypic. As such, these recommendations are based on a patient’s treatment experience instead of genotype.

HIV/HCV coinfection: Recommendations for treatment of chronic HCV infection in patients with HIV are the same as those for patients who do not have HIV, but attention to potential drug-drug interactions between DAAs and antiretrovirals is needed (see Box 1, below). Clinicians are encouraged to consult a specialist in the treatment of liver disease or viral hepatitis and an experienced HIV care provider as needed.

KEY POINTS
  • The choice of regimen should be based on individual pretreatment assessment findings, HCV treatment history, and insurance coverage.
  • The recommended regimens within each list are in alphabetical order, not in order of preference; no single regimen is recommended over another within each list of options.

Undetectable or indeterminate genotype: Rarely, laboratories report the results of an HCV genotype test as “undetectable” or “indeterminate” for a patient with detectable HCV viral load Germer, et al. 2011. These HCV genotype reports are consistent with active HCV infection. The laboratory may be able to clarify the specific reason for the result. For example, an “undetectable” result may be due to the lower sensitivity of the genotype test compared with the HCV RNA test or a level of HCV RNA that is too low to perform the assay for genotype.

Data on treating patients with HCV who have an undetectable or indeterminate genotype are limited. Patients who have an undetectable or indeterminate HCV genotype can be treated with a pangenotypic regimen such as glecaprevir/pibrentasvir or sofosbuvir/velpatasvir.

Table 1, below, lists recommended oral DAAs. All regimens listed in drug regimen tables for all HCV genotypes refer to oral medications.

Notes:

  1. Age ≥18 years old.
  2. Glecaprevir/pibrentasvir (GLE/PIB; Mavyret) is indicated for individuals ≥3 years old or weighing ≥45 kg with chronic HCV genotype 1, 2, 3, 4, 5, or 6. See prescribing information for full indications, dosing regimens, and information.
  3. Ledipasvir/sofosbuvir (LED/SOF; Harvoni; multiple brands) is indicated for individuals ≥3 years old with chronic HCV genotype 1, 4, 5, or 6. See prescribing information for full indications, dosing regimens, and information.
Table 1: Recommended Oral Direct-Acting Antiviral Drug Regimens for Adults [a] With Chronic HCV (October 2022)
Drug/Combination Trade Name
Glecaprevir/pibrentasvir Mavyret [b]
Ledipasvir/sofosbuvir Multiple brands [c]
Sofosbuvir/velpatasvir Multiple brands
Sofosbuvir/velpatasvir/voxilaprevir Vosevi

Drug-drug interactions: It is essential to check current resources for potential drug-drug interactions before prescribing direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) treatment.

Box 1: Online Resources for Identifying Drug-Drug Interactions Associated With DAAs

Recommended Treatment Regimens for Treatment-Naive Patients

Recommended regimens: The recommendations are organized by whether or not the patient has compensated cirrhosis. All drugs in the recommended regimens listed below are oral medications.

Treatment interruption and adherence: To achieve HCV cure, strict adherence to the medications as prescribed is essential. Before initiating treatment with a DAA regimen, develop an adherence plan with the patient, address potential barriers, and make support available if it is needed. Clinicians are advised to consult an HCV treatment specialist if a patient’s DAA treatment is interrupted.

Drug names: A “/” between 2 drug names indicates a co-formulated tablet.

Rating of regimens: All regimen choices listed below are rated A1 (strong recommendation, with high-quality evidence from at least 1 randomized trial with clinical outcomes or validated laboratory endpoints) except where indicated.

Abbreviations: HCV, hepatitis C virus; RAS, resistance-associated substitution; RBV, ribavirin.

Notes:

  1. Asselah, et al. 2018Zeuzem, et al. 2018Kwo, et al. 2017
  2. Brown, et al. 2019Forns, et al. 2017
  3. Feld, et al. 2015Foster, et al. 2015
  4. Zeuzem, et al. 2018Kwo, et al. 2017
  5. Brown, et al. 2019Gane(b), et al. 2016
  6. Foster, et al. 2015
  7. Esteban, et al. 2018Foster, et al. 2015
  8. Patients with genotype 3 and compensated cirrhosis require baseline NS5A RAS testing. Those without Y93H can be treated with 12 weeks of sofosbuvir/velpatasvir, and those with the Y93H RAS can be treated with sofosbuvir/velpatasvir plus weight-based RBV Esteban, et al. 2018.
Table 2: Preferred Regimens for HCV Treatment-Naive Patients
Genotype Regimen Treatment Duration
No
Cirrhosis
Compensated
Cirrhosis
1a, 1b, 2, 4, 5, 6 Glecaprevir 300 mg/pibrentasvir 120 mg once daily 8 weeks [a] 8 weeks [b]
Sofosbuvir 400 mg/velpatasvir 100 mg once daily 12 weeks [c] 12 weeks [c]
3 Glecaprevir 300 mg/pibrentasvir 120 mg once daily 12 weeks [d] 12 weeks [e]
Sofosbuvir 400 mg/velpatasvir 100 mg once daily 12 weeks [f] 12 weeks [g,h]

Download Table 2: Preferred Regimens for HCV Treatment-Naive Patients Printable PDF

Abbreviation: HCV, hepatitis C virus.

Notes:

  1. Kowdley, et al. 2017Terrault, et al. 2016Kowdley, et al. 2014
  2. Terrault, et al. 2016Reddy, et al. 2015
  3. Terrault, et al. 2016
  4. Abergel, et al. 2016Kohli, et al. 2015
Table 3: Alternative Regimens for HCV Treatment-Naive Patients
Genotype/Patient Characteristics Regimen Treatment Duration
No
Cirrhosis
Compensated
Cirrhosis
1a or 1b, non-Black, HIV-negative, HCV RNA <6 mil copies/mL (A2) Ledipasvir 90 mg/sofosbuvir 400 mg once daily 8 weeks [a] 12 weeks [b]
1a or 1b, Black, HIV-positive or HCV RNA >6 mil copies/mL (A2) Ledipasvir 90 mg/sofosbuvir 400 mg once daily 12 weeks [a] 12 weeks [c]
4, 5, 6 Ledipasvir 90 mg/sofosbuvir 400 mg once daily 12 weeks [d] 12 weeks [d]

Download Table 3: Alternative Regimens for HCV Treatment-Naive Patients Printable PDF

Recommended regimens: The recommendations are organized by whether or not the patient has compensated cirrhosis. All drugs in the recommended regimens listed below are oral medications.

Treatment interruption and adherence: To achieve HCV cure, strict adherence to the medications as prescribed is essential. Before initiating treatment with a DAA regimen, develop an adherence plan with the patient, address potential barriers, and make support available if it is needed. Clinicians are advised to consult an HCV treatment specialist if a patient’s DAA treatment is interrupted.

Drug names: A “/” between 2 drug names indicates a co-formulated tablet.

Rating of regimens: All regimen choices listed below are rated A1 (strong recommendation, with high-quality evidence from at least 1 randomized trial with clinical outcomes or validated laboratory endpoints) except where indicated.

Abbreviations: PEG-IFN, pegylated interferon; RAS, resistance-associated substitution; RBV, ribavirin.

Notes:

  1. Kwo, et al. 2017
  2. FDA(b) 2019
  3. Feld, et al. 2015Foster, et al. 2015
  4. Foster, et al. 2015
  5. Patients with genotype 3 and compensated cirrhosis require baseline NS5A RAS testing. Those without Y93H can be treated with 12 weeks of sofosbuvir/velpatasvir, and those with the Y93H RAS can be treated with sofosbuvir/velpatasvir plus weight-based RBV Esteban, et al. 2018.
Table 4: Preferred Regimens After PEG-IFN Plus RBV Treatment Failure
Genotype Regimen Treatment Duration
No
Cirrhosis
Compensated
Cirrhosis
1a, 1b, 2, 4, 5, 6 Glecaprevir 300 mg/pibrentasvir 120 mg once daily 8 weeks [a] 12 weeks [b]
Sofosbuvir 400 mg/velpatasvir 100 mg once daily 12 weeks [c] 12 weeks [c]
3 Glecaprevir 300 mg/pibrentasvir 120 mg once daily 16 weeks [a] 16 weeks [b]
Sofosbuvir 400 mg/velpatasvir 100 mg once daily 12 weeks [d] 12 weeks [d,e]

Download Table 4: Preferred Regimens After PEG-IFN Plus RBV Treatment Failure Printable PDF

Abbreviations: PEG-IFN, pegylated interferon; RBV, ribavirin.

Notes:

  1. Afdhal, et al. 2014Lawitz, et al. 2014
  2. Kohli, et al. 2015
Table 5: Alternative Regimens After PEG-IFN Plus RBV Treatment Failure
Genotype Regimen Treatment Duration
No
Cirrhosis
Compensated
Cirrhosis
1a, 1b Ledipasvir 90 mg/sofosbuvir 400 mg once daily 12 weeks [a] 12 weeks [a]
Ledipasvir 90 mg/sofosbuvir 400 mg once daily plus weight-based RBV twice daily Not indicated 12 weeks [a]
4, 5, 6 Ledipasvir 90 mg/sofosbuvir 400 mg once daily 12 weeks [b] 12 weeks [b]

Download Table 5: Alternative Regimens After PEG-IFN Plus RBV Treatment Failure Printable PDF

Recommended DAA Retreatment Regimens

Recommended regimens: The recommendations are organized by whether or not the patient has compensated cirrhosis. All drugs in the recommended regimens listed below are oral medications.

Treatment interruption and adherence: To achieve HCV cure, strict adherence to the medications as prescribed is essential. Before initiating treatment with a DAA regimen, develop an adherence plan with the patient, address potential barriers, and make support available if it is needed. Clinicians are advised to consult an HCV treatment specialist if a patient’s DAA treatment is interrupted.

Drug names: A “/” between 2 drug names indicates a co-formulated tablet.

Rating of regimens: All regimen choices listed below are rated A1 (strong recommendation, with high-quality evidence from at least 1 randomized trial with clinical outcomes or validated laboratory endpoints) except where indicated.

Abbreviations: DAA, direct-acting antiviral; RBV, ribavirin.

Notes:

  1. Lok, et al. 2019Poordad, et al. 2017
  2. Not recommended for NS3/4 protease inhibitor inclusive combination DAA regimens.
  3. Bourliere, et al. 2018Bourliere, et al. 2017Gane(a), et al. 2016
  4. Bourliere, et al. 2018Bourliere, et al. 2017
Table 6: Recommended Regimens After Sofosbuvir or Elbasvir/Grazoprevir Treatment Failure
Genotype Regimen Treatment Duration
No
Cirrhosis
Compensated
Cirrhosis
1a, 1b, 2, 4, 5, 6 Glecaprevir 300 mg/pibrentasvir 120 mg once daily 16 weeks [a,b] 16 weeks [b]
Sofosbuvir 400 mg/velpatasvir 100 mg/voxilaprevir 100 mg once daily 12 weeks [c] 12 weeks [c]
3 Sofosbuvir 400 mg/velpatasvir 100 mg/voxilaprevir 100 mg once daily plus weight-based RBV twice daily 12 weeks [d] 12 weeks [d]

Download Table 6: Recommended Regimens After Sofosbuvir or Elbasvir/Grazoprevir Treatment Failure Printable PDF

Abbreviation: RBV, ribavirin.

Notes:

  1. Wyles, et al. 2019Poordad, et al. 2017
  2. FDA(b) 2019Wyles, et al. 2019
  3. Pearlman, et al. 2019Bourliere, et al. 2017Gane(a), et al. 2016
  4. Bourliere, et al. 2017Gane(a), et al. 2016
  5. Addition of weight-based RBV is recommended.
Table 7: Recommended Regimens After Glecaprevir/Pibrentasvir Treatment Failure
Genotype Regimen Treatment Duration
No
Cirrhosis
Compensated
Cirrhosis
1a, 1b, 2, 3, 4, 5, 6 Glecaprevir 300 mg/pibrentasvir 120 mg plus  sofosbuvir 400 mg once daily plus weight-based RBV twice daily 16 weeks [a] 16 weeks [b]
Sofosbuvir 400 mg/velpatasvir 100 mg/voxilaprevir 100 mg once daily 12 weeks [c] 12 weeks [d,e]

Download Table 7: Recommended Regimens After Glecaprevir/Pibrentasvir Treatment Failure Printable PDF

Monitoring During DAA Treatment

RECOMMENDATIONS
Monitoring of Patients Taking RBV
  • While patients are taking RBV, clinicians should perform hemoglobin testing at weeks 2 and 4 of treatment and every 4 weeks thereafter until therapy is complete. (A1)
Monitoring for HBV Reactivation
  • In patients who are HBsAg-positive and have no detectable HBV DNA, clinicians should monitor for HBV reactivation by performing AST, ALT, and HBV DNA tests every 4 weeks during HCV treatment. (A3)
  • Clinicians new to HCV treatment should consult a liver disease or experienced viral hepatitis specialist for further evaluation of patients who develop detectable HBV DNA. (A3)

Abbreviations: ALT, alanine transaminase; AST, aspartate aminotransferase; HBsAg, HBV surface antigen; HBV, hepatitis B virus; HCV, hepatitis C virus; RBV, ribavirin.

The adverse events associated with direct-acting antiviral (DAA) treatment are listed in Table 8, below, and most are manageable. Patients who are taking RBV and experience insomnia may need to adjust the timing of the dose to earlier in the afternoon to avoid any sleep disruption.

KEY POINT
  • HCV RNA testing is needed only at baseline and at least 12 weeks after treatment is finished; HCV RNA testing is not necessary during or at the completion of treatment.

Transient transaminase and bilirubin elevations may occur during the normal course of DAA therapy. However, severe laboratory value elevations and rare hepatic decompensation have been reported with protease inhibitors during the treatment of patients with cirrhosis FDA(b) 2019FDA 2017FDA(b) 2016Hayashi, et al. 2016. Therefore, if the ALT level is elevated above baseline 4 weeks after treatment is initiated, testing should be repeated and levels monitored according to the drug’s prescribing information FDA(b) 2019FDA 2017FDA(b) 2016Hayashi, et al. 2016.

HBV reactivation and HBV-related hepatic flares have occurred both during and after DAA therapy in patients not receiving HBV treatment Wang, et al. 2017Sulkowski, et al. 2016Collins, et al. 2015Ende, et al. 2015. The U.S. Food and Drug Administration has issued a drug safety warning regarding these risks.

Sources: FDA(a) 2019FDA(b) 2019FDA 2017FDA(a) 2016FDA(b) 2016Hayashi, et al. 2016FDA 2011
Table 8: Adverse Events Associated with Direct-Acting Antivirals
Drug or Combination
(brand name)
Most Common Adverse Reactions (proportion observed)
Glecaprevir/pibrentasvir
(GLE/PIB; Mavyret)
Headache and fatigue (>10%)
Ledipasvir/sofosbuvir
(LED/SOF; Harvoni; multiple brands)
Asthenia, headache, and fatigue (≥10%)
Ribavirin
(Copegus)
Fatigue/asthenia, pyrexia, myalgia, and headache in adults receiving combination therapy (>40%)
Sofosbuvir/velpatasvir
(SOF/VEL; Epclusa; multiple brands)
  • With SOF/VEL: headache and fatigue (≥10%, all grades)
  • With SOF/VEL and ribavirin in patients with decompensated cirrhosis: fatigue, anemia, nausea, headache, insomnia, and diarrhea (≥10%, all grades)
Sofosbuvir/velpatasvir/voxilaprevir
(SOF/VEL/VOX; Vosevi)
Headache, fatigue, diarrhea, and nausea (≥10%)

Post-Treatment Care

RECOMMENDATIONS
Evaluating the Response to HCV Treatment
  • Clinicians should perform HCV RNA testing 12 weeks after treatment is complete to verify that an SVR has been achieved. (A1)
  • If SVR is achieved, as established by undetectable HCV RNA at 12 weeks after treatment, clinicians should:
    • Inform their patients that the HCV infection has been cured. (A2)
    • Explain the risk of HCV reinfection and that HCV antibodies are not protective against reinfection. (A1)
  • To assess for reinfection in patients with ongoing risk factors, clinicians should perform follow-up screening with HCV RNA testing (not HCV antibody testing) at least annually, even with a history of an SVR. (A1)
  • If HCV RNA is detectable at 12 weeks after treatment, clinicians should:
    • Inform patients that treatment has failed. (A1)
    • If new to HCV treatment, consult with a liver disease specialist for retreatment evaluation. (B3)
    • See the guideline section Recommended DAA Retreatment Regimens.
Post-Treatment Monitoring
  • For patients taking RBV-containing HCV treatment regimens, clinicians should:
    • Advise female and male patients to take extreme care to avoid pregnancy for 6 months after completion of therapy. (A2)
    • Counsel female and male patients on effective contraceptive use. (A2)
  • If an individual becomes pregnant within 6 months of completing an RBV-containing HCV treatment regimen, clinicians should discuss the risks of using DAAs and RBV during pregnancy. (A3)
Patients With Persistent Liver Disease
  • Clinicians should evaluate patients with persistent abnormal transaminase levels after SVR for other causes of liver disease and consult with a liver disease specialist. (A3)
  • For patients with bridging fibrosis or cirrhosis at the onset of treatment, clinicians should continue screening for HCC with ultrasound and alpha-fetoprotein testing every 6 months indefinitely. (A1)
  • Clinicians should refer patients with cirrhosis to a liver disease specialist for continued care. (A3)

Abbreviations: DAA, direct-acting antiviral; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; RBV, ribavirin; SVR, sustained viral response.

After treatment for chronic HCV infection, follow-up care is based on individual patient factors, including response to recent treatment, previous treatment history, degree of hepatic fibrosis, comorbidities, and cofactors for other sources of liver injury, such as alcohol use or fatty liver disease.

Evaluating the Response to HCV Treatment

All treated individuals should have HCV RNA testing performed 12 weeks after treatment. If there is no detectable HCV RNA at 12 weeks, HCV infection has been cured. In the absence of recurrent risk factors, subsequent HCV testing is not required. However, with late relapse reported in rare (<0.5%) cases, some clinicians may choose to retest at 24 and/or 48 weeks after the end of treatment Jacobson, et al. 2017.

Successful treatment of chronic HCV infection results in no detectable HCV RNA, but antibodies to HCV are typically retained for life. It is important for treated individuals to understand that they will continue to have antibodies but not active HCV infection. It is also important for patients to understand that, although antibodies to HCV will continue to be present after treatment, HCV antibodies do not offer protection from HCV reinfection. All individuals with no detectable HCV RNA are susceptible to reinfection if re-exposed to HCV. Although the overall rate of reinfection is low, it is elevated among populations at higher risk Martinello, et al. 2017. A meta-analysis of 59 studies reporting recurrence after an SVR in 9,049 patients found that the summary 5-year risk of HCV reinfection among high-risk populations was 10.67% Simmons, et al. 2016. High risk was defined as having 1 or more risk factors, currently or formerly, for reinfection (injection drug use, imprisonment, and being a man who has sex with other men). Among low-risk populations, defined as those with no known risk factors, the summary 5-year recurrence risk was 0.95% Simmons, et al. 2016. For discussion of risk factors, see the NYSDOH AI guideline Hepatitis C Virus Screening, Testing, and Diagnosis in Adults.

Post-Treatment Monitoring

It is important to monitor the resolution of patients’ HCV treatment-related adverse events. RBV-containing regimens are teratogenic; patients receiving RBV-containing regimens and their partners should be counseled to avoid pregnancy during treatment and up to 6 months post-treatment. Two forms of effective birth control should be used FDA 2011.

Table 8: Adverse Events Associated with Direct-Acting Antivirals provides a list of adverse events associated with DAA regimens. During treatment with RBV, patients may experience hemolytic anemia, nausea, cough, shortness of breath, rash, dry skin, pruritus, lactic acidosis, or pancreatitis FDA 2011. Patients should be monitored through the follow-up period for resolution of any symptoms.

Hepatitis B virus (HBV) reactivation: HBV-related hepatic flares have been reported during and after DAA therapy in patients who were not receiving concurrent HBV treatment Wang, et al. 2017De Monte, et al. 2016Hayashi, et al. 2016Sulkowski, et al. 2016Takayama, et al. 2016Collins, et al. 2015Ende, et al. 2015. The U.S. Food and Drug Administration has issued a drug safety warning regarding these risks. Although data are insufficient to make a definitive recommendation regarding monitoring in patients with isolated hepatitis B core antibody AASLD/IDSA 2021, it is important to consider HBV reactivation as part of the differential diagnosis for patients with HBV infection who experience unexplained increases in liver enzymes during or after completion of DAA treatment.

Patients With Persistent Liver Disease

Cessation of fibrosis progression and histological improvement are among the benefits of treating chronic HCV infection. However, patients should still be monitored for potential post-treatment decompensation Jacobson, et al. 2017. Individuals cured of HCV infection remain at risk of liver disease progression if they have advanced baseline fibrosis, other chronic liver conditions (e.g., chronic HBV, non-alcoholic fatty liver disease), comorbidities (e.g., metabolic syndrome, alcohol use, uncontrolled coinfection with HIV), or at risk of liver injury from drugs or dietary supplements Vandenbulcke, et al. 2016.

There is wide individual variation in the time needed for fibrosis progression in patients with chronic liver disease. It is important to maintain an elevated suspicion for progression and the complications associated with hepatic decompensation, particularly in individuals with bridging fibrosis or cirrhosis before the initiation of DAA therapy and HCV cure.

In patients with bridging fibrosis or cirrhosis, an ultrasound and alpha-fetoprotein testing should be performed every 6 months, regardless of SVR, to screen for HCC Jacobson, et al. 2017. The risk of HCC for patients with stage 3 or higher fibrosis is 1.5% to 5% per year, but it is not known whether the histologic improvement after successful treatment mitigates this risk Bruix and Sherman 2011.

All Recommendations

ALL RECOMMENDATIONS: TREATMENT OF CHRONIC HEPATITIS C VIRUS INFECTION IN ADULTS

Considerations in HCV Treatment

  • Before initiating antiviral therapy, clinicians should assess CrCl, HIV and HBV status, and the degree of fibrosis, among other factors. (A1)
  • Clinicians new to HCV treatment should consult a specialist in treatment of liver disease or viral hepatitis when treating patients who:
    • Have severe renal impairment (CrCl <30 mL/min) and/or are undergoing hemodialysis. (A3)
    • Require retreatment after treatment failure of any DAA regimen. (B3)
  • Clinicians should prescribe RBV with caution for patients with a CrCl <50 mL/min. (A1)
    • If prescribed, a reduced dose of 200 mg per day is required.
    • Non-RBV-containing regimens can be prescribed without dose adjustments for patients with CrCl ≥30 mL/min.
Contraindications
  • Clinicians should not prescribe RBV for treatment of the following patients:
    • Female or male patients planning conception within 6 months of the last dose of RBV. (A2)
    • Male patients who have pregnant partners. (A2)
HCV Testing and Management in Pregnant Adults
  • Clinicians should perform HCV testing in all patients who are planning to get pregnant (A2) or are currently pregnant (B3), and screening should be repeated with each pregnancy (B3).
  • Clinicians should advise pregnant patients diagnosed with chronic HCV (a positive HCV antibody test result and detectable HCV RNA) to defer treatment with DAAs until they are no longer pregnant or breastfeeding. (A2)
  • If an individual with HCV becomes pregnant during DAA treatment, the clinician should:
    • Advise that the use of DAAs is not currently recommended during pregnancy because of insufficient safety data on the effect on the fetus.
    • Discuss the risks and benefits of continuing treatment.
  • Clinicians should refer pregnant patients diagnosed with HCV to a specialist experienced in managing HCV in pregnancy, e.g., hepatologist, gastroenterologist, infectious disease specialist, or high-risk obstetrician. (A3)
  • If a pregnant patient with HCV has a substance use disorder, the clinician should provide or refer the patient for substance use treatment, including harm reduction services. (A3)
  • Clinicians should advise pregnant and postpartum individuals with HCV monoinfection that HCV is not transmitted through breast milk and breastfeeding is considered safe. (B3)
  • Clinicians should advise patients to discontinue breastfeeding if they have or develop cracked or bleeding nipples and to express and discard milk until the bleeding has resolved. (B3)
  • Clinicians should refer infants born to mothers with HCV to pediatricians with experience in HCV care. (A3)
Contraceptive Use With HCV Treatment Containing RBV
  • Before initiating RBV as part of an HCV treatment regimen in a patient of childbearing potential, clinicians should confirm a negative pregnancy test and advise patients to use 2 methods of birth control for the duration of DAA therapy and 6 months after completion. (A2)
  • If a patient becomes pregnant while taking RBV, the clinician should discontinue the RBV. (A1)
  • Contraindication: Clinicians should not prescribe RBV for any patient planning pregnancy within 6 months of the last RBV dose or any male patient with a pregnant partner. (A2)
Monitoring of Patients Taking RBV
  • While patients are taking RBV, clinicians should perform hemoglobin testing at weeks 2 and 4 of treatment and every 4 weeks thereafter until therapy is complete. (A1)
Monitoring for HBV Reactivation
  • In patients who are HBsAg-positive and have no detectable HBV DNA, clinicians should monitor for HBV reactivation by performing AST, ALT, and HBV DNA tests every 4 weeks during HCV treatment. (A3)
  • Clinicians new to HCV treatment should consult a liver disease or experienced viral hepatitis specialist for further evaluation of patients who develop detectable HBV DNA. (A3)
Evaluating the Response to HCV Treatment
  • Clinicians should perform HCV RNA testing 12 weeks after treatment is complete to verify that an SVR has been achieved. (A1)
  • If SVR is achieved, as established by undetectable HCV RNA at 12 weeks after treatment, clinicians should:
    • Inform their patients that the HCV infection has been cured. (A2)
    • Explain the risk of HCV reinfection and that HCV antibodies are not protective against reinfection. (A1)
  • To assess for reinfection in patients with ongoing risk factors, clinicians should perform follow-up screening with HCV RNA testing (not HCV antibody testing) at least annually, even with a history of an SVR. (A1)
  • If HCV RNA is detectable at 12 weeks after treatment, clinicians should:
    • Inform patients that treatment has failed. (A1)
    • If new to HCV treatment, consult with a liver disease specialist for retreatment evaluation. (B3)
    • See the guideline section Recommended DAA Retreatment Regimens.
Post-Treatment Monitoring
  • For patients taking RBV-containing HCV treatment regimens, clinicians should:
    • Advise female and male patients to take extreme care to avoid pregnancy for 6 months after completion of therapy. (A2)
    • Counsel female and male patients on effective contraceptive use. (A2)
  • If an individual becomes pregnant within 6 months of completing an RBV-containing HCV treatment regimen, clinicians should discuss the risks of using DAAs and RBV during pregnancy. (A3)
Patients With Persistent Liver Disease
  • Clinicians should evaluate patients with persistent abnormal transaminase levels after SVR for other causes of liver disease and consult with a liver disease specialist. (A3)
  • For patients with bridging fibrosis or cirrhosis at the onset of treatment, clinicians should continue screening for HCC with ultrasound and alpha-fetoprotein testing every 6 months indefinitely. (A1)
  • Clinicians should refer patients with cirrhosis to a liver disease specialist for continued care. (A3)

Abbreviations: AASLD, American Association for the Study of Liver Diseases; ALT, alanine transaminase; AST, aspartate aminotransferase; CDC, Centers for Disease Control and Prevention; CrCl, creatinine clearance; DAA, direct-acting antiviral; HBsAg, HBV surface antigen; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; IDSA, Infectious Diseases Society of America; PEG-IFN, pegylated interferon; RAS, resistance-associated substitution; RBV, ribavirin; SVR, sustained viral response.

Shared Decision-Making

Download Printable PDF of Shared Decision-Making Statement

Date of current publication: August 8, 2023
Lead authors:
Jessica Rodrigues, MS; Jessica M. Atrio, MD, MSc; and Johanna L. Gribble, MA
Writing group: Steven M. Fine, MD, PhD; Rona M. Vail, MD; Samuel T. Merrick, MD; Asa E. Radix, MD, MPH, PhD; Christopher J. Hoffmann, MD, MPH; Charles J. Gonzalez, MD
Committee: Medical Care Criteria Committee
Date of original publication: August 8, 2023

Rationale

Throughout its guidelines, the New York State Department of Health (NYSDOH) AIDS Institute (AI) Clinical Guidelines Program recommends “shared decision-making,” an individualized process central to patient-centered care. With shared decision-making, clinicians and patients engage in meaningful dialogue to arrive at an informed, collaborative decision about a patient’s health, care, and treatment planning. The approach to shared decision-making described here applies to recommendations included in all program guidelines. The included elements are drawn from a comprehensive review of multiple sources and similar  attempts to define shared decision-making, including the Institute of Medicine’s original description [Institute of Medicine 2001]. For more information, a variety of informative resources and suggested readings are included at the end of the discussion.

Benefits

The benefits to patients that have been associated with a shared decision-making approach include:

  • Decreased anxiety [Niburski, et al. 2020; Stalnikowicz and Brezis 2020]
  • Increased trust in clinicians [Acree, et al. 2020; Groot, et al. 2020; Stalnikowicz and Brezis 2020]
  • Improved engagement in preventive care [McNulty, et al. 2022; Scalia, et al. 2022; Bertakis and Azari 2011]
  • Improved treatment adherence, clinical outcomes, and satisfaction with care [Crawford, et al. 2021; Bertakis and Azari 2011; Robinson, et al. 2008]
  • Increased knowledge, confidence, empowerment, and self-efficacy [Chen, et al. 2021; Coronado-Vázquez, et al. 2020; Niburski, et al. 2020]

Approach

Collaborative care: Shared decision-making is an approach to healthcare delivery that respects a patient’s autonomy in responding to a clinician’s recommendations and facilitates dynamic, personalized, and collaborative care. Through this process, a clinician engages a patient in an open and respectful dialogue to elicit the patient’s knowledge, experience, healthcare goals, daily routine, lifestyle, support system, cultural and personal identity, and attitudes toward behavior, treatment, and risk. With this information and the clinician’s clinical expertise, the patient and clinician can collaborate to identify, evaluate, and choose from among available healthcare options [Coulter and Collins 2011]. This process emphasizes the importance of a patient’s values, preferences, needs, social context, and lived experience in evaluating the known benefits, risks, and limitations of a clinician’s recommendations for screening, prevention, treatment, and follow-up. As a result, shared decision-making also respects a patient’s autonomy, agency, and capacity in defining and managing their healthcare goals. Building a clinician-patient relationship rooted in shared decision-making can help clinicians engage in productive discussions with patients whose decisions may not align with optimal health outcomes. Fostering open and honest dialogue to understand a patient’s motivations while suspending judgment to reduce harm and explore alternatives is particularly vital when a patient chooses to engage in practices that may exacerbate or complicate health conditions [Halperin, et al. 2007].

Options: Implicit in the shared decision-making process is the recognition that the “right” healthcare decisions are those made by informed patients and clinicians working toward patient-centered and defined healthcare goals. When multiple options are available, shared decision-making encourages thoughtful discussion of the potential benefits and potential harms of all options, which may include doing nothing or waiting. This approach also acknowledges that efficacy may not be the most important factor in a patient’s preferences and choices [Sewell, et al. 2021].

Clinician awareness: The collaborative process of shared decision-making is enhanced by a clinician’s ability to demonstrate empathic interest in the patient, avoid stigmatizing language, employ cultural humility, recognize systemic barriers to equitable outcomes, and practice strategies of self-awareness and mitigation against implicit personal biases [Parish, et al. 2019].

Caveats: It is important for clinicians to recognize and be sensitive to the inherent power and influence they maintain throughout their interactions with patients. A clinician’s identity and community affiliations may influence their ability to navigate the shared decision-making process and develop a therapeutic alliance with the patient and may affect the treatment plan [KFF 2023; Greenwood, et al. 2020]. Furthermore, institutional policy and regional legislation, such as requirements for parental consent for gender-affirming care for transgender people or insurance coverage for sexual health care, may infringe upon a patient’s ability to access preventive- or treatment-related care [Sewell, et al. 2021].

Figure 1: Elements of Shared Decision-Making

Figure 1: Elements of Shared Decision-Making

Download figure: Elements of Shared Decision-Making

Health equity: Adapting a shared decision-making approach that supports diverse populations is necessary to achieve more equitable and inclusive health outcomes [Castaneda-Guarderas, et al. 2016]. For instance, clinicians may need to incorporate cultural- and community-specific considerations into discussions with women, gender-diverse individuals, and young people concerning their sexual behaviors, fertility intentions, and pregnancy or lactation status. Shared decision-making offers an opportunity to build trust among marginalized and disenfranchised communities by validating their symptoms, values, and lived experience. Furthermore, it can allow for improved consistency in patient screening and assessment of prevention options and treatment plans, which can reduce the influence of social constructs and implicit bias [Castaneda-Guarderas, et al. 2016].

Clinician bias has been associated with health disparities and can have profoundly negative effects [FitzGerald and Hurst 2017; Hall, et al. 2015]. It is often challenging for clinicians to recognize and set aside personal biases and to address biases with peers and colleagues. Consciously or unconsciously, negative or stigmatizing assumptions are often made about patient characteristics, such as race, ethnicity, gender, sexual orientation, mental health, and substance use [Avery, et al. 2019; van Boekel, et al. 2013; Livingston, et al. 2012]. With its emphasis on eliciting patient information, a shared decision-making approach encourages clinicians to inquire about patients’ lived experiences rather than making assumptions and to recognize the influence of that experience in healthcare decision-making.

Stigma: Stigma may prevent individuals from seeking or receiving treatment and harm reduction services [Tsai, et al. 2019]. Among people with HIV, stigma and medical mistrust remain significant barriers to healthcare utilization, HIV diagnosis, and medication adherence and can affect disease outcomes [Turan, et al. 2017; Chambers, et al. 2015], and stigma among clinicians against people who use substances has been well-documented [Stone, et al. 2021; Tsai, et al. 2019; van Boekel, et al. 2013]. Sexual and reproductive health, including strategies to prevent HIV transmission, acquisition, and progression, may be subject to stigma, bias, social influence, and violence.

SHARED DECISION-MAKING IN HIV CARE
  • As prevention and treatment modalities in HIV care expand (i.e., vaccines, barriers, injectables, implants, on-demand therapies), it is important for clinicians to ask patients about their goals for prevention and treatment rather than assume that efficacy is the primary factor in patient preference [Sewell, et al. 2021].
  • The shared decision-making approach to clinical care enhances patient knowledge and uptake of new technologies and behavioral practices that align with the patient’s unique preferences and identity [Sewell, et al. 2021], ensures that the selection of a care plan is mutually agreed upon, and considers the patient’s ability to effectively use and adhere to the selected course of prevention or treatment.

Resources and Suggested Reading

In addition to the references cited below, the following resources and suggested reading may be useful to clinicians.

RESOURCES
References

Acree ME, McNulty M, Blocker O, et al. Shared decision-making around anal cancer screening among black bisexual and gay men in the USA. Cult Health Sex 2020;22(2):201-16. [PMID: 30931831]

Avery JD, Taylor KE, Kast KA, et al. Attitudes toward individuals with mental illness and substance use disorders among resident physicians. Prim Care Companion CNS Disord 2019;21(1):18m02382. [PMID: 30620451]

Bertakis KD, Azari R. Patient-centered care is associated with decreased health care utilization. J Am Board Fam Med 2011;24(3):229-39. [PMID: 21551394]

Castaneda-Guarderas A, Glassberg J, Grudzen CR, et al. Shared decision making with vulnerable populations in the emergency department. Acad Emerg Med 2016;23(12):1410-16. [PMID: 27860022]

Chambers LA, Rueda S, Baker DN, et al. Stigma, HIV and health: a qualitative synthesis. BMC Public Health 2015;15:848. [PMID: 26334626]

Chen CH, Kang YN, Chiu PY, et al. Effectiveness of shared decision-making intervention in patients with lumbar degenerative diseases: a randomized controlled trial. Patient Educ Couns 2021;104(10):2498-2504. [PMID: 33741234]

Coronado-Vázquez V, Canet-Fajas C, Delgado-Marroquín MT, et al. Interventions to facilitate shared decision-making using decision aids with patients in primary health care: a systematic review. Medicine (Baltimore) 2020;99(32):e21389. [PMID: 32769870]

Coulter A, Collins A. Making shared decision-making a reality: no decision about me, without me. 2011. https://www.kingsfund.org.uk/sites/default/files/Making-shared-decision-making-a-reality-paper-Angela-Coulter-Alf-Collins-July-2011_0.pdf

Crawford J, Petrie K, Harvey SB. Shared decision-making and the implementation of treatment recommendations for depression. Patient Educ Couns 2021;104(8):2119-21. [PMID: 33563500]

FitzGerald C, Hurst S. Implicit bias in healthcare professionals: a systematic review. BMC Med Ethics 2017;18(1):19. [PMID: 28249596]

Greenwood BN, Hardeman RR, Huang L, et al. Physician-patient racial concordance and disparities in birthing mortality for newborns. Proc Natl Acad Sci U S A 2020;117(35):21194-21200. [PMID: 32817561]

Groot G, Waldron T, Barreno L, et al. Trust and world view in shared decision making with indigenous patients: a realist synthesis. J Eval Clin Pract 2020;26(2):503-14. [PMID: 31750600]

Hall WJ, Chapman MV, Lee KM, et al. Implicit racial/ethnic bias among health care professionals and its influence on health care outcomes: a systematic review. Am J Public Health 2015;105(12):e60-76. [PMID: 26469668]

Halperin B, Melnychuk R, Downie J, et al. When is it permissible to dismiss a family who refuses vaccines? Legal, ethical and public health perspectives. Paediatr Child Health 2007;12(10):843-45. [PMID: 19043497]

Institute of Medicine. Crossing the quality chasm: a new health system for the 21st century. 2001. https://www.ncbi.nlm.nih.gov/books/NBK222274/

KFF. Key data on health and health care by race and ethnicity. 2023 Mar 15. https://www.kff.org/racial-equity-and-health-policy/report/key-data-on-health-and-health-care-by-race-and-ethnicity/ [accessed 2023 May 19]

Livingston JD, Milne T, Fang ML, et al. The effectiveness of interventions for reducing stigma related to substance use disorders: a systematic review. Addiction 2012;107(1):39-50. [PMID: 21815959]

McNulty MC, Acree ME, Kerman J, et al. Shared decision making for HIV pre-exposure prophylaxis (PrEP) with black transgender women. Cult Health Sex 2022;24(8):1033-46. [PMID: 33983866]

Niburski K, Guadagno E, Abbasgholizadeh-Rahimi S, et al. Shared decision making in surgery: a meta-analysis of existing literature. Patient 2020;13(6):667-81. [PMID: 32880820]

Parish SJ, Hahn SR, Goldstein SW, et al. The International Society for the Study of Women’s Sexual Health process of care for the identification of sexual concerns and problems in women. Mayo Clin Proc 2019;94(5):842-56. [PMID: 30954288]

Robinson JH, Callister LC, Berry JA, et al. Patient-centered care and adherence: definitions and applications to improve outcomes. J Am Acad Nurse Pract 2008;20(12):600-607. [PMID: 19120591]

Scalia P, Durand MA, Elwyn G. Shared decision-making interventions: an overview and a meta-analysis of their impact on vaccine uptake. J Intern Med 2022;291(4):408-25. [PMID: 34700363]

Sewell WC, Solleveld P, Seidman D, et al. Patient-led decision-making for HIV preexposure prophylaxis. Curr HIV/AIDS Rep 2021;18(1):48-56. [PMID: 33417201]

Stalnikowicz R, Brezis M. Meaningful shared decision-making: complex process demanding cognitive and emotional skills. J Eval Clin Pract 2020;26(2):431-38. [PMID: 31989727]

Stone EM, Kennedy-Hendricks A, Barry CL, et al. The role of stigma in U.S. primary care physicians’ treatment of opioid use disorder. Drug Alcohol Depend 2021;221:108627. [PMID: 33621805]

Tsai AC, Kiang MV, Barnett ML, et al. Stigma as a fundamental hindrance to the United States opioid overdose crisis response. PLoS Med 2019;16(11):e1002969. [PMID: 31770387]

Turan B, Budhwani H, Fazeli PL, et al. How does stigma affect people living with HIV? The mediating roles of internalized and anticipated HIV stigma in the effects of perceived community stigma on health and psychosocial outcomes. AIDS Behav 2017;21(1):283-91. [PMID: 27272742]

van Boekel LC, Brouwers EP, van Weeghel J, et al. Stigma among health professionals towards patients with substance use disorders and its consequences for healthcare delivery: systematic review. Drug Alcohol Depend 2013;131(1-2):23-35. [PMID: 23490450]

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Updates, Authorship, and Related Guidelines

Updates, Authorship, and Related Guidelines
Date of original publication July 31, 2017
Date of current publication April 17, 2023
Highlights of changes, additions, and updates in the April 17, 2023 edition
  • Recommended DAA Treatment Regimens: The recommendation on how to choose an anti-HCV regimen was revised; choosing a regimen is based on findings from the pretreatment assessment and history of HCV treatment and not HCV genotype. Accordingly, the tables of recommended treatment regimens were revised.
  • Post-Treatment Care: A recommendation was added for clinicians to refer patients with cirrhosis to a liver disease specialist for continued care.
  • Note: The NYSDOH AI guideline Treatment of Chronic HCV with Direct-Acting Antivirals (July 2017 through October 2020) was replaced with 3 guidelines: 1) Hepatitis C Virus Screening, Testing and Diagnosis in Adults; 2) Pretreatment Assessment in Adults With Chronic Hepatitis C Virus Infection; and 3) Treatment of Chronic Hepatitis C Virus Infection in Adults
Intended users Clinicians in New York State who treat adults with chronic HCV
Lead author

David E. Bernstein, MD

Writing group

Joshua S. Aron, MD; Christine A. Kerr, MD; Colleen Flanigan, RN, MS; Christopher J. Hoffmann, MD, MPH; Charles J. Gonzalez, MD

Author and writing group conflict of interest disclosures There are no author or writing group conflict of interest disclosures.
Committee

Hepatitis C Virus (HCV) Guideline Committee

Developer and funder

New York State Department of Health AIDS Institute (NYSDOH AI)

Development process

See Guideline Development and Recommendation Ratings Scheme, below.

Related NYSDOH AI guidelines

Guideline Development and Recommendation Ratings

Guideline Development: New York State Department of Health AIDS Institute Clinical Guidelines Program
Program manager Clinical Guidelines Program, Johns Hopkins University School of Medicine, Division of Infectious Diseases. See Program Leadership and Staff.
Mission To produce and disseminate evidence-based, state-of-the-art clinical practice guidelines that establish uniform standards of care for practitioners who provide prevention or treatment of HIV, viral hepatitis, other sexually transmitted infections, and substance use disorders for adults throughout New York State in the wide array of settings in which those services are delivered.
Expert committees The NYSDOH AI Medical Director invites and appoints committees of clinical and public health experts from throughout New York State to ensure that the guidelines are practical, immediately applicable, and meet the needs of care providers and stakeholders in all major regions of New York State, all relevant clinical practice settings, key New York State agencies, and community service organizations.
Committee structure
  • Leadership: AI-appointed chair, vice chair(s), chair emeritus, clinical specialist(s), JHU Guidelines Program Director, AI Medical Director, AI Clinical Consultant, AVAC community advisor
  • Contributing members
  • Guideline writing groups: Lead author, coauthors if applicable, and all committee leaders
Disclosure and management of conflicts of interest
  • Annual disclosure of financial relationships with commercial entities for the 12 months prior and upcoming is required of all individuals who work with the guidelines program, and includes disclosure for partners or spouses and primary professional affiliation.
  • The NYSDOH AI assesses all reported financial relationships to determine the potential for undue influence on guideline recommendations and, when indicated, denies participation in the program or formulates a plan to manage potential conflicts. Disclosures are listed for each committee member.
Evidence collection and review
  • Literature search and review strategy is defined by the guideline lead author based on the defined scope of a new guideline or update.
  • A comprehensive literature search and review is conducted for a new guideline or an extensive update using PubMed, other pertinent databases of peer-reviewed literature, and relevant conference abstracts to establish the evidence base for guideline recommendations.
  • A targeted search and review to identify recently published evidence is conducted for guidelines published within the previous 3 years.
  • Title, abstract, and article reviews are performed by the lead author. The JHU editorial team collates evidence and creates and maintains an evidence table for each guideline.
Recommendation development
  • The lead author drafts recommendations to address the defined scope of the guideline based on available published data.
  • Writing group members review the draft recommendations and evidence and deliberate to revise, refine, and reach consensus on all recommendations.
  • When published data are not available, support for a recommendation may be based on the committee’s expert opinion.
  • The writing group assigns a 2-part rating to each recommendation to indicate the strength of the recommendation and quality of the supporting evidence. The group reviews the evidence, deliberates, and may revise recommendations when required to reach consensus.
Review and approval process
  • Following writing group approval, draft guidelines are reviewed by all contributors, program liaisons, and a volunteer reviewer from the AI Community Advisory Committee.
  • Recommendations must be approved by two-thirds of the full committee. If necessary to achieve consensus, the full committee is invited to deliberate, review the evidence, and revise recommendations.
  • Final approval by the committee chair and the NYSDOH AI Medical Director is required for publication.
External reviews
  • External review of each guideline is invited at the developer’s discretion.
  • External reviewers recognized for their experience and expertise review guidelines for accuracy, balance, clarity, and practicality and provide feedback.
Update process
  • JHU editorial staff ensure that each guideline is reviewed and determined to be current upon the 3-year anniversary of publication; guidelines that provide clinical recommendations in rapidly changing areas of practice may be reviewed annually. Published literature is surveilled to identify new evidence that may prompt changes to existing recommendations or development of new recommendations.
  • If changes in the standard of care, newly published studies, new drug approval, new drug-related warning, or a public health emergency indicate the need for immediate change to published guidelines, committee leadership will make recommendations and immediate updates and will invite full committee review as indicated.
Recommendation Ratings Scheme
Strength Quality of Evidence
Rating Definition Rating Definition
A Strong 1 Based on published results of at least 1 randomized clinical trial with clinical outcomes or validated laboratory endpoints.
B Moderate * Based on either a self-evident conclusion; conclusive, published, in vitro data; or well-established practice that cannot be tested because ethics would preclude a clinical trial.
C Optional 2 Based on published results of at least 1 well-designed, nonrandomized clinical trial or observational cohort study with long-term clinical outcomes.
2† Extrapolated from published results of well-designed studies (including nonrandomized clinical trials) conducted in populations other than those specifically addressed by a recommendation. The source(s) of the extrapolated evidence and the rationale for the extrapolation are provided in the guideline text. One example would be results of studies conducted predominantly in a subpopulation (e.g., one gender) that the committee determines to be generalizable to the population under consideration in the guideline.
3 Based on committee expert opinion, with rationale provided in the guideline text.

Last updated on February 8, 2024