HCV-HIV Co-infected Patient Cohort in Thailand

Response to Peg-interferon and Ribavirin for the Treatment of HCV Infection in HIV Co-infected Patients, Implemented in Public Hospitals in Thailand

This is a study of HCV treatment using the standard regimen of pegylated-interferon plus ribavirin in HIV co-infected patients participating in the PHPT cohort study. The treatment will be implemented in conjunction with gastro-enterologists/hepatologists by internists responsible for the participant's HIV treatment.

Chronic hepatitis C virus (HCV) infection is responsible for several severe and life threatening complications, which are worsened by HIV co-infection. HIV-HCV co-infected patients are at a higher risk of death compared to HIV mono-infected individuals, even if HIV replication is suppressed on antiretroviral treatment.

The goal of HCV antiviral treatment is to cure HCV infection. Curing HCV infection allows fibrosis regression, improved clinical outcomes. In addition, individuals who have been cured are no longer contagious to other individuals, therefore widespread access to HCV treatment may contribute to the control of the HCV epidemic.

A combination of injectable pegylated-interferon with oral ribavirin is currently the recommended regimen for the treatment of hepatitis C in the setting of HIV co-infection. They are administered for 24 weeks in HCV mono-infected patients but need to be administered for one year in HIV-HCV co-infected patients. Newer drugs, such as the first generation HCV protease inhibitors (boceprevir, telaprevir), administered concomitantly, are used in patients who have not been cured using peg-interferon + ribavirin, and may allow for shorter treatment.

PRIMARY OBJECTIVE

1. To determine the percentage of patients according to genotypes with sustained virological response 6 months after treatment discontinuation (SVR).

HCV TREATMENT

• Peg-interferon alpha 2-b (a subcutaneous injection of 1.5 micrograms/kg once a week)
• Ribavirin dosing according to HCV genotype and body weight; dose adjustment in case of anemia.

A total of 60 patients could be enrolled in the study: 15 HCV-HIV co-infected patients in a first part (starting in August 2014) and 45 patients in a second part, depending on funding.

Study Overview

• Status: Completed
• Conditions: HIV; Hepatitis C Infection
• Intervention / Treatment: Drug: Peg-interferon + ribavirin under HIV physician supervision

Detailed Description

Study Population Screening: HIV infected patients with a positive anti-HCV test will be approached for screening if they are at least 18 years old, participate in the PHPT cohort study, have evidence of control of HIV replication and have a CD4 cell count ≥200 cells/mm3 if currently receiving antiretroviral HIV treatment (on the same anti-HIV regimen for at least 12 weeks); or HIV RNA load ≤5000 copies/ml CD4 cells ≥500 cells/mm3if not receiving antiretroviral treatment.

Inclusion Criteria

• Evidence of chronic HCV infection for at least 6 months before study entry (at least one detectable HCV viral load, i.e. ≥17 IU/mL, with an antibody test positive at least 6 months before the HCV RNA load result)
• Fibrosis Stage F2-3-4 determined by transient elastography (Fibroscan or other similar equipment). During the first part of the study, priority will be given to patients with Fibrosis Stage F2-3.
• Negative pregnancy test (on the day of inclusion). Main exclusion criteria
• Anemia and thrombocytopenia
• Severe liver damage, advanced stage cirrhosis or cancer
• Uncontrolled diabetes, Uncontrolled thyroid dysfunction
• Retinopathy
• Creatinine clearance <50 mL/min (Cockcroft)
• Disease associated with the immune system
• Significant heart problems
• Severe neuropsychiatric conditions
• Contra-indication to study treatment (including pregnancy or lack of effective contraception in the participant or female partner)
• Other exclusion criteria related to the use of ribavirin and peg-interferon
• Any conditions that, in the investigator's judgment, may compromise the follow up.

Follow up After HCV treatment initiation, patients will be monitored for safety and antiviral efficacy at 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48 weeks (end of treatment) and 6 months after treatment discontinuation.

Treatment will be discontinued earlier in patients who do not achieve early viral response, i.e. a decrease of at least 2 log10 HCV RNA IU/mL after the first 12 weeks of HCV therapy.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 4

Contacts and Locations

Study Locations

• Thailand
  • Chiang Mai, Thailand, 50180
    • Nakornping Hospital
  • Chiang Rai, Thailand, 57000
    • Chiangrai Prachanukroh Hospital
  • Chon Buri, Thailand, 20000
    • Chonburi Hospital
  • Samut Sakhon, Thailand, 74000
    • Samutsakhon Hospital
  • Chiang Mai
    • San Pa Tong, Chiang Mai, Thailand, 50120
      • Sanpatong Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Evidence of chronic HCV infection for at least 6 months before study entry (at least one detectable HCV viral load, i.e. ≥17 IU/mL, with an antibody test positive at least 6 months before the HCV RNA load result)
• Fibrosis Stage F2-3-4 determined by transient elastography (Fibroscan or other similar equipment). During the first part of the study, priority will be given to patients with Fibrosis Stage F2-3.
• Negative pregnancy test (on the day of inclusion).

Exclusion Criteria:

• Anemia and thrombocytopenia
• Severe liver damage, advanced stage cirrhosis or cancer
• Uncontrolled diabetes, Uncontrolled thyroid dysfunction
• Retinopathy
• Creatinine clearance <50 mL/min (Cockcroft)
• Disease associated with the immune system
• Significant heart problems
• Severe neuropsychiatric conditions Contra-indication to study treatment (including pregnancy or lack of effective contraception in the participant or female partner)
• Other exclusion criteria related to the use of ribavirin and peg-interferon
• Any conditions that, in the investigator's judgment, may compromise the follow up.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: PegINF-ribavirin; Peg-interferon + ribavirin under HIV physician supervision Peg-interferon alpha 2-b initial dosing is 1.5 micrograms/kg (subcutaneous injection) once a week Ribavirin initial dosing in the morning and in the evening: For genotypes 2, 3: ribavirin 400 mg (i.e. 800 mg daily).; For genotypes 1, 4, 5 and 6:800 mg/day, if bodyweight <65 kg,1000 mg/day, if bodyweight between 66-80 kg,1200 mg/day, if bodyweight between 81-105 kg,1400 mg/day, if bodyweight >105 kg. Duration: 48 weeks

Drug: Peg-interferon + ribavirin under HIV physician supervision; Peg-interferon + ribavirin under HIV physician supervision; Other Names: Pegintron, Rebetol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Sustained Virological Response 6 Months After Treatment Discontinuation	Number of Participants with Sustained Virological Response 6 Months After Treatment Discontinuation,	6 months after end of treatment, i.e. 1.5 years after treatment initiation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With at Least a Serious Adverse Events Associated With Study Treatment (Peg-interferon and Ribavirin)	Number of participants with at least a serious adverse events associated with study treatment (peg-interferon and ribavirin).	From initiation of treatment to 6 months after treatment discontinuation
Number of Participants Grouped by HIV-1 RNA Concentrations	Number of participants grouped by HIV-1 RNA concentrations (Detected vs. Not Detected).	At time of treatment discontinuation (whatever its date) and 6 months thereafter

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Completed the First 24 and 48 Weeks of Treatment	Number of participants completed the first 24 and 48 weeks of treatment.	From initiation of treatment to the first 48 weeks of treatment
Number of Adverse Events by Severity Grade	Number of adverse events (AE) by severity grade. The severity grading scale is based on the DAIDS grading table, the grading scale ranging from grades 1 to 5: Grade 1 indicates a mild event, Grade 2 indicates a moderate event, Grade 3 indicates a severe event, Grade 4 indicates a potentially life-threatening event, and Grade 5 indicates death.	From initiation of treatment to 6 months after treatment discontinuation
Number of Participants Able to Perform Self-injections of Peg-interferon	Number of participants able to perform self-injections of peg-interferon.	From initiation of treatment to the first 48 weeks of treatment
Number of Participants With Ribavirin Compliance at ≥ 95%, 80% - 95%, and < 80%	Number of participants with ribavirin compliance at ≥ 95%, 80% - 95%, and < 80%.	From initiation of treatment to the first 48 weeks of treatment

Collaborators and Investigators

• Sponsor: Institut de Recherche pour le Developpement
• Collaborators: Ministry of Health, Thailand

Study record dates

Study Major Dates

• Study Start: August 1, 2014
• Primary Completion (Actual): May 1, 2017
• Study Completion (Actual): January 1, 2018

Study Registration Dates

• First Submitted: September 9, 2014
• First Submitted That Met QC Criteria: September 19, 2014
• First Posted (Estimate): September 25, 2014

Study Record Updates

• Last Update Posted (Actual): June 3, 2019
• Last Update Submitted That Met QC Criteria: February 22, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: ribavirin; HIV; HCV; Thailand; pegylated interferon
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Hepatitis; Infections; Hepatitis C; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Antineoplastic Agents; Interferons; Ribavirin
• Other Study ID Numbers: PHPT-HCV