About the study (objectives)
This study will examine the feasibility of switching antiretroviral therapies (ART) followed by antiviral treatment for hepatitis C for co-infected people receiving methadone as opioid substitution therapy in Regina, Saskatchewan. Specifically, participants will switch to E/C/F/TAF (elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide) and then receive SOF/VEL (sofosbuvir/velpatasvir).
About the disease/condition (background/context)
Injection drug use is the primary risk factor for HIV in Saskatchewan, a province where incidence rates of HIV are double those of the rest of Canada. In 2011, over three quarters of HIV cases in Saskatchewan were due to injection drug use, compared to only one in five in the rest of the country. A significant number of people in this population are also living with hepatitis C virus (HCV) and many are current receiving opioid substitution therapy (OST), including methadone.
For people receiving methadone, regular trips to community pharmacies can help to improve adherence to other medications, like HIV and HCV antiviral therapies. The regimens used in this study are once daily and one pill each, characteristics which will help to optimize and monitor treatment adherence in this group. Although E/C/F/TAF and SOL/VEL have been tested independently, they have not been adequately studied in combination or in persons receiving OST.
As a feasibility study, the primary goal of the study is to assess how willing people are to switch their antiviral regimen and how adherent people were once they switched. The researchers are also interested in assessing the safety and success of this regimen in this specific population (HIV/HCV positive and receiving methadone treatment), information which may provide justification for this approach in the future. The data gathered in this study will also inform the feasibility of future clinical trials that aim to evaluate new or under-studied treatment strategies in non-traditional patient populations such as those on OST and those who use injection drugs.
Study Approach (methodology)
On the first study visit, participants will undergo a regular clinical assessment as well as bone and kidney health testing. Participants will switch to E/C/F/TAF and be monitored for 12 weeks. Following this period, the HCV antiviral regimen (SOF/VEL) will be added to the regimen for a further 12 weeks — all study drugs will be dispensed during daily visits to community pharmacies. After completion of the SOF/VEL treatment, study participants will visit their physicians for assessments at 12- and 24-weeks post-treatment.
- 18 years of age or older
- HIV positive and HCV positive for minimum of 6 months
- Have not taken E/C/F/TAF at any point previously.
- HIV RNA ≤ 50 c/mL at screening and ≤ 200 c/mL for at least 3 months prior to screening.
- CD4 ≥ 200 cells/uL at screening.
- On stable methadone as opioid substitution therapy for at least 3 months prior to screening; other forms of OST such as suboxone are not permitted.
- Treatment naïve to all anti-HCV therapy, or treatment experienced, except any NS5A inhibitors.
- Must be willing and able to understand the requirements of study participation and provide signed and dated written informed consent prior to screening.
- Female subjects are willing to use acceptable methods of birth control.
- Have received any anti-HCV therapy previously with NS5A inhibitors.
- Have any evidence of decompensated liver disease.
- Co-infection with hepatitis B.
- Has cirrhosis and liver imaging within 6 months of Day 1 showing evidence of hepatocellular carcinoma (HCC), or is under evaluation for HCC.
- Use of drugs with contraindication or drug-interactions with E/C/F/TAF or SOF/VEL.
- Have any active contraindication to the use of methadone
- Use of alcohol to a degree deemed by the investigator to be dangerous in conjunction with methadone.
- Has documented historic resistance to any of the components of E/C/F/TAF.
- Has an eGFR (by MDRD equation) < 30 mL/min.
- Is pregnant, breast-feeding, or planning or suspected to get pregnant.
- Participants who are involved in any other interventional HIV or HCV studies during the study period.
Regina General Hospital
If you would like more information on this clinical study, please refer to clinicaltrials.gov.
Dr. Alexander Wong
University of Saskatchewan
Dr. Stuart Skinner
Infectious Diseases Physician
Regina Qu’Appelle Health Region