Observed histological outcomes in chronic hepatitis B patients at Year 1 and 5

Histological Response Cirrhotic Subjects Non-Cirrhotic Subjects
Histological Response

Liver histological outcomes

Observed histological response rates at Year 1 and Year 5

Of the originally randomized and treated subjects, liver biopsy data from 51% of subjects (328/641; cirrhotics n=93, non-cirrhotics n=235) who received open-label treatment with VIREAD monotherapy were available for analysis at baseline, Week 48, and Week 240.

There were no apparent differences between the subset of subjects who had liver biopsy data at Week 240 and those subjects remaining on open-label VIREAD without biopsy data that would be expected to affect histological outcomes at Week 240. No definitive conclusions can be established about the remaining study population that was not part of this subset analysis.1

Observed histological response rates at Week 48 and Week 240

aHistological response was defined as Knodell necroinflammatory score improvement of ≥2 points, without worsening in Knodell fibrosis score.

Study 102 and 103 clinical trial design

In Studies 102 (HBeAg–, N=375) and 103 (HBeAg+, N=266), a combined total of 641 adult patients with chronic hepatitis B (CHB) and compensated liver disease who were primarily nucleoside–treatment-naïve entered a 48-week, randomized, double-blind, active-controlled treatment period comparing VIREAD 300 mg to adefovir dipivoxil 10 mg.1

Subjects who completed double-blind treatment at Week 48 were eligible to roll over with no interruption in treatment to open-label VIREAD. Of 641 patients enrolled in the initial trials, 412 (64%) completed 384 weeks of treatment.1

The primary endpoint in Study 102 and Study 103 was complete response to treatment at 48 weeks as defined by HBV DNA <400 copies/mL (69 IU/mL) + histological response (Knodell necroinflammatory score improvement of ≥2 points without worsening in Knodell fibrosis score).1

Cirrhotic Subjects

Observed cirrhosis regression

Regression of cirrhosis was observed in patients with cirrhosis at baseline.1

Of the originally randomized and treated subjects, liver biopsy data from 51% of subjects (328/641; cirrhotics n=93, non-cirrhotics n=235) who received open-label treatment with VIREAD monotherapy were available for analysis at baseline, Week 48, and Week 240.

There were no apparent differences between the subset of subjects who had liver biopsy data at Week 240 and those subjects remaining on open-label VIREAD without biopsy data that would be expected to affect histological outcomes at Week 240. No definitive conclusions can be established about the remaining study population that was not part of this subset analysis.1

Observed cirrhosis regression in cirrhotic subjects
  • In 93 subjects with cirrhosis at baseline (Ishak fibrosis score 5-6), 97% and 99% had either improvement or no change in Ishak fibrosis score at Week 48 and Week 240, respectively1
Change in Ishak Fibrosis Score in Adult Subjects with Cirrhosis

aRegression of cirrhosis was defined as a reduction in Ishak fibrosis score of ≥2 points.

  • At Week 48: From a baseline Ishak fibrosis score of 5-6, 28 subjects (30%) had a decrease of ≥1 point (1 decreased by 1 point, 14 decreased by 2 points, 11 decreased by 3 points, 2 decreased by 4 points), 62 subjects (67%) had no change, and 3 subjects (3%) had an increase of 1 point2
Non-Cirrhotic Subjects

Observed regression or no change in Ishak fibrosis score

Improvement or no change in fibrosis was observed in patients without cirrhosis at baseline.1

Of the originally randomized and treated subjects, liver biopsy data from 51% of subjects (328/641; cirrhotics n=93, non-cirrhotics n=235) who received open-label treatment with VIREAD monotherapy were available for analysis at baseline, Week 48, and Week 240. Observed histological response rates for VIREAD subjects (n=328) were 80% at Week 48 and 88% at Week 240.

There were no apparent differences between the subset of subjects who had liver biopsy data at Week 240 and those subjects remaining on open-label VIREAD without biopsy data that would be expected to affect histological outcomes at Week 240. No definitive conclusions can be established about the remaining study population that was not part of this subset analysis.1

Observed improvement or no change in Ishak fibrosis score in non-cirrhotic subjects
Change in Ishak Fibrosis Score in Non-Cirrhotic Adult Subjects
  • At Week 48: From a baseline Ishak fibrosis score of 0-4, 45 subjects (19%) had a decrease of 1 to 2 points, 171 subjects (73%) had no change, and 19 subjects (8%) had an increase of ≥1 point (16 increased by 1 point, 2 increased by 3 points, and 1 increased by 5 points)2

Indication and Usage

VIREAD® is indicated for the treatment of chronic hepatitis B in adults and pediatric patients 12 years of age and older. The following points should be considered when initiating therapy with VIREAD for the treatment of HBV infection:

  • The indication in adults is based on data from treatment of subjects who were nucleoside–treatment-naïve and treatment-experienced with documented resistance to lamivudine. Subjects were adults with HBeAg-positive and HBeAg-negative chronic hepatitis B with compensated liver disease
  • VIREAD was evaluated in a limited number of subjects with chronic hepatitis B and decompensated liver disease
  • The numbers of subjects in clinical trials who had adefovir resistance-associated substitutions at baseline were too small to reach conclusions of efficacy

Important Safety Information

Dosage and Administration

  • Recommended dose, in adults and pediatric patients ≥12 years of age (≥35 kg), for the treatment of chronic hepatitis B: one 300 mg tablet, once daily, taken orally, without regard to food
  • In the treatment of chronic hepatitis B, the optimal duration of treatment is unknown
  • Safety and efficacy in pediatric patients <12 years of age or weighing <35 kg with chronic hepatitis B have not been established
  • The dosing interval of VIREAD should be adjusted (using recommendations in the table below) and renal function closely monitored in patients with baseline creatinine clearance <50 mL/min

Dosage Adjustment for Patients with Altered Creatinine Clearance


  • aCalculated using ideal (lean) body weight. bGenerally once weekly assuming three hemodialysis sessions a week of approximately 4 hours duration. VIREAD should be administered following completion of dialysis.
  • The pharmacokinetics of tenofovir have not been evaluated in non-hemodialysis patients with creatinine clearance <10 mL/min; therefore, no dosing recommendation is available for these patients

Dosage Adjustment for Patients with Altered Creatinine Clearance (cont'd)

  • No dose adjustment is necessary for patients with mild renal impairment (creatinine clearance 50-80 mL/min). Routine monitoring of estimated creatinine clearance, serum phosphorus, urine glucose, and urine protein should be performed in these patients
  • No data are available to make dose recommendations in pediatric patients with renal impairment

Indication and Usage

VIREAD® (tenofovir disoproxil fumarate) is indicated for the treatment of chronic hepatitis B in adults and pediatric patients 12 years of age and older.

The following points should be considered when initiating therapy with VIREAD for the treatment of HBV infection:

  • The indication in adults is based on data from treatment of subjects who were nucleoside–treatment-naÏve and treatment-experienced with documented resistance to lamivudine. Subjects were adults with HBeAg-positive and HBeAg-negative chronic hepatitis B with compensated liver disease
  • VIREAD was evaluated in a limited number of subjects with chronic hepatitis B and decompensated liver disease
  • The numbers of subjects in clinical trials who had adefovir resistance-associated substitutions at baseline were too small to reach conclusions of efficacy

Important Safety Information

TAP for Important Safety Information, including Boxed Warning on lactic acidosis, severe hepatomegaly with steatosis and post treatment exacerbation of hepatitis.

BOXED WARNING: LACTIC ACIDOSIS/SEVERE HEPATOMEGALY WITH STEATOSIS and POST TREATMENT EXACERBATION OF HEPATITIS

  • Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs, including VIREAD, in combination with other antiretrovirals
  • Severe acute exacerbations of hepatitis have been reported in HBV-infected patients who have discontinued anti-hepatitis B therapy, including VIREAD. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue anti-hepatitis B therapy, including VIREAD. If appropriate, resumption of anti-hepatitis B therapy may be warranted

Warnings and Precautions

  • New onset or worsening renal impairment: Cases of acute renal failure and Fanconi syndrome have been reported with the use of VIREAD. In all patients, assess estimated creatinine clearance (CrCl) prior to initiating and during therapy. In patients at risk for renal dysfunction, including those who previously experienced renal events while receiving adefovir dipivoxil, additionally monitor serum phosphorus, urine glucose, and urine protein. In patients with CrCl <50 mL/min, adjust dosing interval and closely monitor renal function. Avoid concurrent or recent use with a nephrotoxic agent. Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after initiation of high dose or multiple NSAIDs in HIV-infected patients with risk factors for renal dysfunction; consider alternatives to NSAIDs in these patients. Persistent or worsening bone pain, pain in extremities, fractures and/or muscular pain or weakness may be manifestations of proximal renal tubulopathy and should prompt an evaluation of renal function
  • Coadministration with other products:
    • Do not use in combination with other products containing tenofovir disoproxil fumarate
    • Do not administer in combination with adefovir dipivoxil
  • Patients coinfected with HIV‑1 and HBV: Due to the risk of development of HIV‑1 resistance, VIREAD should only be used in HIV‑1 and HBV coinfected patients as part of an appropriate antiretroviral combination regimen. HIV‑1 antibody testing should be offered to all HBV-infected patients before initiating therapy with VIREAD
  • Bone effects: Decreases in bone mineral density (BMD) and mineralization defects, including osteomalacia, have been seen in patients treated with VIREAD. Consider assessment of BMD in adult and pediatric patients who have a history of pathologic bone fracture or other risk factors for bone loss. In a clinical trial conducted in pediatric subjects 12 to <18 years of age with chronic hepatitis B, total body BMD gain was less in VIREAD-treated subjects as compared to the control group. In patients at risk of renal dysfunction who present with persistent or worsening bone or muscle symptoms, hypophosphatemia and osteomalacia secondary to proximal renal tubulopathy should be considered

Adverse Reactions

  • In HBV-infected subjects with compensated liver disease: Most common adverse reaction (all grades) was nausea (9%). Other treatment-emergent adverse reactions reported in >5% of patients treated with VIREAD included: abdominal pain, diarrhea, headache, dizziness, fatigue, nasopharyngitis, back pain, and skin rash
  • In HBV-infected subjects with decompensated liver disease: Most common adverse reactions (all grades) reported in ≥10% of patients treated with VIREAD were abdominal pain (22%), nausea (20%), insomnia (18%), pruritus (16%), vomiting (13%), dizziness (13%), and pyrexia (11%)

Drug Interactions

  • Didanosine: Coadministration increases didanosine concentrations. Use with caution and monitor for evidence of didanosine toxicity (e.g., pancreatitis, neuropathy). Didanosine should be discontinued in patients who develop didanosine-associated adverse reactions. In patients weighing >60 kg, the didanosine dose should be reduced to 250 mg once daily when it is coadministered with VIREAD and in patients weighing <60 kg, the didanosine dose should be reduced to 200 mg once daily when coadministered with VIREAD
  • HIV‑1 protease inhibitors: Coadministration decreases atazanavir concentrations and increases tenofovir concentrations; use atazanavir given with ritonavir. Coadministration of VIREAD with atazanavir and ritonavir, darunavir and ritonavir, or lopinavir/ritonavir increases tenofovir concentrations. Monitor for evidence of tenofovir toxicity
  • Hepatitis C antivirals: Coadministration of VIREAD with HARVONI increases VIREAD exposure; monitor for adverse reactions associated with VIREAD. Consider an alternative HCV or HIV‑1 therapy in patients receiving VIREAD concomitantly with HARVONI and an HIV‑1 protease inhibitor with ritonavir or cobicistat
  • Drugs affecting renal function: Coadministration of VIREAD with drugs that reduce renal function or compete for active tubular secretion may increase concentrations of tenofovir

Dosage and Administration

  • Recommended dose, in adults and pediatric patients ≥12 years of age (≥35 kg), for the treatment of chronic hepatitis B: one 300 mg tablet, once daily, taken orally, without regard to food
  • In the treatment of chronic hepatitis B, the optimal duration of treatment is unknown
  • Safety and efficacy in pediatric patients <12 years of age or weighing <35 kg with chronic hepatitis B have not been established
  • The dosing interval of VIREAD should be adjusted (using recommendations in the table below) and renal function closely monitored in patients with baseline creatinine clearance <50 mL/min

Dosage Adjustment for Patients with Altered Creatinine Clearance

Dosage Table

aCalculated using ideal (lean) body weight.

bGenerally once weekly assuming three hemodialysis sessions a week of approximately 4 hours duration. VIREAD should be administered following completion of dialysis.

  • The pharmacokinetics of tenofovir have not been evaluated in non-hemodialysis patients with creatinine clearance <10 mL/min; therefore, no dosing recommendation is available for these patients
  • No dose adjustment is necessary for patients with mild renal impairment (creatinine clearance 50-80 mL/min). Routine monitoring of estimated creatinine clearance, serum phosphorus, urine glucose, and urine protein should be performed in these patients
  • No data are available to make dose recommendations in pediatric patients with renal impairment

Indication and Usage

VIREAD® (tenofovir disoproxil fumarate) is indicated for the treatment of chronic hepatitis B in adults and pediatric patients 12 years of age and older.

The following points should be considered when initiating therapy with VIREAD for the treatment of HBV infection:

  • The indication in adults is based on data from treatment of subjects who were nucleoside–treatment-naÏve and treatment-experienced with documented resistance to lamivudine. Subjects were adults with HBeAg-positive and HBeAg-negative chronic hepatitis B with compensated liver disease
  • VIREAD was evaluated in a limited number of subjects with chronic hepatitis B and decompensated liver disease
  • The numbers of subjects in clinical trials who had adefovir resistance-associated substitutions at baseline were too small to reach conclusions of efficacy
Please click here to see full Prescribing Information, including BOXED WARNING.

Reference: 1. VIREAD Prescribing Information, Foster City, CA: Gilead Sciences, Inc.; February 2016.

References: 1. VIREAD Prescribing Information, Foster City, CA: Gilead Sciences, Inc.; February 2016. 2. Data on file, Gilead Sciences, Inc. DOF 0102_0103_Ishak. Gilead Sciences, Inc.

References: 1. VIREAD Prescribing Information, Foster City, CA: Gilead Sciences, Inc.; February 2016. 2. Data on file, Gilead Sciences, Inc. DOF 0102_0103_Ishak. Gilead Sciences, Inc.

This information is intended for US healthcare professionals

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