Switch to Genvoya Followed by HCV Therapy With Epclusa Followed by Simplification of HIV Therapy With Biktarvy in Patients With HIV-HCV Co-Infected Subjects on Opioid Substitution Therapy

• Status: Recruiting
• Trial end date: 2021-06-22
• Target enrollment: 0
• Participant gender: All

Summary

The study hypothesis is to determine the feasibility of switching HIV-HCV co-infected patients receiving methadone or buprenorphine/naloxone as opioid substitution therapy with suppressed HIV RNA viral load on current antiretroviral therapy to elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF, Genvoya™) followed by 12 weeks of HCV antiviral therapy with sofosbuvir/velpatasvir (SOF/VEL, Epclusa™), followed then by switch to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF, Biktarvy™) for an additional 48 weeks.

• Phase: Phase 4
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Saskatchewan Health Authority - Regina Area
• Collaborator: Gilead Sciences
• Treatments: Analgesics, Opioid; Cobicistat; Elvitegravir; Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Emtricitabine; Emtricitabine tenofovir alafenamide; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Methadone; Sofosbuvir; Sofosbuvir-velpatasvir drug combination; Tenofovir; Velpatasvir

Criteria

Inclusion Criteria:

1. Male and Females, 18 years or older

2. HIV infected (ELISA with western blot confirmation)

3. HCV RNA positive for minimum of 6 months / Genotype 1-6

4. Prescribed a combination ART regimen (cART) that may include any DHHS recommended or alternative regimens, which the treating physician considers is appropriate for their patient, except E/C/F/TAF or B/F/TAF at any point previously.

5. HIV RNA ≤ 50 c/mL at screening and ≤ 200 c/mL for at least 3 months prior to screening.

6. CD4 ≥ 200 cells/uL at screening.

7. Stage 0 to 4 fibrosis.

8. On methadone or buprenorphine/naloxone as OST for at least 3 months prior to screening and deemed stable on OST by the investigator.

9. Treatment naïve to all anti-HCV therapy, or treatment experienced but with no previous exposure to NS5A inhibitors.

10. Ability to remain adherent to medications and study protocol as per investigator opinion

11. Must be willing and able to understand the requirements of study participation and provide signed and dated written informed consent prior to screening.

12. Female subjects are willing to use acceptable methods of birth control as defined in the protocol.

Exclusion Criteria:

1. Have received any anti-HCV therapy previously with NS5A inhibitors. Previous treatment regimens allowed may include pegylated interferon, ribavirin, 1st generation NS3/NS4 protease inhibitors (telaprevir or boceprevir), and sofosbuvir.

2. Have any evidence of decompensated liver disease including ascites, esophageal or gastric variceal bleeding, hepatic encephalopathy, or other symptoms suggestive of advanced liver disease. For cirrhotic patients with Child-Pugh Class B or C or with Pugh-Turcotte (CPT) score greater than 6 must be excluded.

3. Co-infection with hepatitis B.

4. Has cirrhosis and liver imaging within 6 months of Day 1 showing evidence of hepatocellular carcinoma (HCC), or is under evaluation for HCC.

5. Concomitant use of drugs with contraindication or drug-interactions with E/C/F/TAF on Day 1 visit or B/F/TAF on Week 48/0E visit. However, the use of any concomitant drugs with contraindication with SOF/VEL are to be stopped during the weeks of treatment (i.e. week 12-24), and only after the Principal Investigator's permission, may the use of these drugs may be continued or restarted after week 24 visit (i.e. end of SOF/VEL therapy).

6. Have any active contraindication to the use of methadone, as listed in the product monograph for methadone and listed below, unless deemed acceptable based on the Principal Investigator's judgement:

1. Patients who are hypersensitive to the active substance (methadone hydrochloride) or other opioid analgesics or to any ingredient in the formulation.

2. Patients with a known or suspected mechanical gastrointestinal obstruction.

3. Patients with a suspected surgical abdomen.

4. Patients with acute asthma or other obstructive airway, and status asthmaticus.

5. Patients with acute respiratory depression, elevated carbon dioxide levels in the blood, and corpulmonale.

6. Patients with acute alcoholism, delirium tremors, and convulsive disorders.

7. Patients with severe central nervous system depression, increased cerebrospinal or intracranial pressure, and head injury.

8. Patients taking monoamine oxidase (MAO) inhibitors (or within 14 days of such therapy).

9. Patients with diarrhea associated with pseudomembranous colitis caused by cephalosporins, lincomycins (including topical clindamycin) or penicillin, or to patients having diarrhea caused by poisoning, until toxic material has been eliminated from the gastrointestinal tract.

7. Concomitant use of alcohol to a degree deemed by the investigator to be dangerous in conjunction with administration of methadone.

8. Has documented historic resistance to any of the components of E/C/F/TAF or B/F/TAF.

9. Has an eGFR (by MDRD equation) < 30 mL/min/1.73m2.

10. Is pregnant, breast-feeding, or planning or suspected to get pregnant.

11. Has any reason, in the opinion of the investigator, which would make the candidate inappropriate for participation in an investigative study involving oral medications.

12. Involved in any other interventional HIV or HCV study during the study period.