Hepatitis C, Chronic, Human Immunodeficiency Virus
Conditions
Keywords
HIV-HCV co-infected, HCV, HIV, Hep C, Hepatitis C, HCV positive
Brief summary
This is an prospective open label pilot study conducted over 32 weeks. A total of 25 eligible participants who are infected with HCV and HIV will be recruited from 2 Canadian HIV Trials Network (CTN) sites (Ottawa Hospital Research Institute and McGill University Health Centre) This study is investigating the effectiveness of a combination of Elvitegravir/Cobicistat/Emtricitabine/ Tenofovir Alafenamide Single Tablet Regimen (E/C/F/TAF STR) for HIV treatment and Harvoni for HCV treatment. This study will assess the effect that the study drug has on the metabolism of sugar, the changes in fat in the bloodstream, and other metabolic changes. Metabolism is the process your body uses to get or make energy from the food you eat. This study may provide information on the impact of liver fibrosis (scarring of liver tissues) on metabolic changes before, during and after HCV antiviral therapy. Drug-drug interactions (DDI) between E/C/F/TAF and LPV-SOF have been well evaluated and no clinically significant interactions have been identified. A switch to E/C/F/TAF in the context of LPV-SOF HCV antiviral treatment preparation may be particularly beneficial because of its: 1. favorable side effect profile 2. once daily STR formulation 3. known DDI profile with LPV-SOF 4. neutral effect on liver fibrosis 5. improved kidney and bone safety profile with the use of TAF Conduct of this study is justified as it: 1. Assesses a minimal pill count and dosing frequency strategy of co-treatment of HIV and HCV using well tolerated medications with an excellent safety profile and known DDI profile. 2. Provides additional safety data for TAF in the HIV-HCV co-infected population. 3. Quantifies adherence and identifies obstacles to full adherence in this population. There is a paucity of data related to DAA adherence in licensing studies. 4. Provides real-world safety and efficacy data to support the public funding for LPV-SOF DAA therapy in HIV-HCV co-infected populations. 5. Provides preliminary data on the immunologic and metabolic consequences of HCV clearance in HIV-HCV co-infection 6. As a pilot study, the information gathered will inform the feasibility of future clinical trials evaluating novel treatment strategies for HIV-HCV co-infected patients.
Detailed description
The availability of interferon (IFN)-free HCV Direct Acting Antiviral (DAA) antiviral therapy such as Ledipasvir-Sofosbuvir (LPV-SOF) allows for broad provision of treatment for populations living with HIV-HCV. Co-infected persons frequently have competing co-morbidities and are at risk for progressive liver disease which makes adherence and combined management of HIV and HCV challenging. Simple, safe, well tolerated regimens with few drug-drug interactions could be highly beneficial in ensuring success of HCV therapy in this population. With this is mind, the optimal management of antiretroviral therapy prior to initiating LPV-SOF treatment remains unclear. E/C/F/TAF \[elvitegravir-cobicistat-emtricitabine-tenofovir alafenamide fumarate (TAF)\] will be assessed in this study because it is formulated as a single tablet which facilitates adherence by once daily dosing and reduced pill count. It is established to be affective at achieving and maintaining HIV virologic suppression. The safety profile of this HIV regimen is excellent. The E/C/F/TAF formulation assessed in this study will contain TAF. This formulation has been evaluated in HIV-infected populations and found to be of equivalent HIV antiviral activity and to have improved impact on renal and bone metabolism \[ref: David Wohl, Anton Pozniak, Melanie Thompson, Edwin DeJesus, Daniel Podzamczer, Jean-Michel Molina, Gordon Crofoot, Christian Callebaut, Hal Martin, Scott McCallister. Tenofovir Alafenamide (TAF) in a Single-Tablet Regimen in Initial HIV-1 Therapy. Conference on Retroviruses and Opportunistic Infections. 113LB. February 23-26, 2015, Seattle, Washington.\]. There is minimal safety data in HIV-HCV co-infection. Drug-drug interactions (DDI) between HIV antiretrovirals and HCV antivirals remain a key obstacle to the safe and effective delivery. The DDI between E/C/F/TAF and LPV-SOF have been well evaluated and no clinically significant interactions have been identified. A switch to E/C/F/TAF in the context of LPV-SOF HCV antiviral treatment preparation may be particularly beneficial because of its: 1. favorable side effect profile 2. once daily STR formulation 3. known DDI profile with LPV-SOF 4. neutral effect on liver fibrosis 5. improved kidney and bone safety profile with the use of TAF Conduct of this study is justified as it: 1. Assesses a minimal pill count and dosing frequency strategy of co-treatment of HIV and HCV using well tolerated medications with an excellent safety profile and known DDI profile (Complera followed by LPV-SOF). Polypharmacy in the co-infected population remains a significant challenge to therapeutic success. 2. Provides additional safety data for TAF in the HIV-HCV co-infected population. 3. Quantifies adherence and identifies obstacles to full adherence in this population. There is a paucity of data related to DAA adherence in licensing studies. 4. Provides real-world safety and efficacy data to support the public funding for LPV-SOF DAA therapy in HIV-HCV co-infected populations. 5. Provides preliminary data on the immunologic and metabolic consequences of HCV clearance in HIV-HCV co-infection 6. As a pilot study, the information gathered will inform the feasibility of future clinical trials evaluating novel treatment strategies for HIV-HCV co-infected patients.
Interventions
DRUGE/C/F/TAF;
Evaluation of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Switch followed by Ledipasvir-Sofosbuvir Antiviral HCV Therapy
Evaluation of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Switch followed by Ledipasvir-Sofosbuvir Antiviral HCV Therapy
Sponsors
Gilead Sciences
CIHR Canadian HIV Trials Network
Ottawa Hospital Research Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* HIV infected (ELISA with western blot confirmation) * HCV RNA positive for minimum of 6 months / Genotype 1 * Prescribed cART that may include any Department of Health and Human Services (DHHS) recommended or alternative regimens, which the treating physician considers, is appropriate for their patient. (We anticipate that approximately 60% will be on HIV protease inhibitor-based regimens). * HIV RNA BLLQ for minimum of 3 months * Stage 3 or 4 fibrosis * No evidence of liver decompensation defined as past or current ascites, bleeding varices or hepatic encephalopathy. Prior interferon, ribavirin and/or HCV protease inhibitor exposure will be allowed with the exception of cirrhotic with a past history of null response to interferon-based therapy. * Ability to remain adherent to medications and study protocol as per investigator opinion * For female subjects, not pregnant, planning or suspected to be pregnant or breast-feeding * Willing to use acceptable methods of birth control, as defined in protocol * Active substance use and/or mental health issues will not be exclusionary assuming other criteria are met. This inclusion will be restricted to those stably housed and engaged in harm reduction strategies. Our intent is to evaluate study participants who are representative of our clinical population and consider 'difficult to cure' compared to populations already evaluated in licensing studies
Exclusion criteria
* Concomitant use of drugs with contraindication drug interactions with E/C/F/TAF of SOF-LDV * History of HIV integrase inhibitors or NRTI resistance mutations * Platelets \<50 x10\^9/L
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of approached patients who agreed to switch from their current Antiretroviral (ARV) regimen and be screened for this study | 52 weeks | Number of patients |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of subjects achieving SVR12 | 24 weeks | HCV RNA at 12 weeks post HCV treatment completion |
| Proportion of subjects maintaining undetectable HIV RNA levels | 32 weeks | HIV RNA below detection throughout study period |
| Proportion of subjects initiating HCV antiviral therapy | 4 weeks | Number of participants |
| Proportion of subjects discontinuing study medications due to adverse events | 32 weeks | Liver enzyme abnormalities |
Other
| Measure | Time frame | Description |
|---|---|---|
| Measures of serial cytokine immune function will be assessed over the duration of the study. | 32 weeks | Blood will be drawn at each time point for measurement of adipokines (e.g. adiponectin, retinal binding protein 4, interleukin 6, resistin, leptin, visfatin and omentin). (Blood volume: 20 ml). |
| Measures of metabolic function (cholesterol) will be assessed over the duration of the study | 32 weeks | Serial measurement of cholesterol at Baseline, week 4, week 12, and 12 weeks post treatment |
| Measures of metabolic function (glucose) will be assessed over the duration of the study | 32 weeks | Serial measurement of glucose at Baseline, week 4, week 12, and 12 weeks post treatment |
| Patient-Focused Outcome - Physical Activity will be evaluated | 32 weeks | International Physical Activity Questionnaire Short-Form (IPAQ-sf) completed at baseline, week 4 and 12 to quantify total physical activity over the past 7 days reported as metabolic equivalent of task (MET) minutes per week across 4 domains: leisure, domestic, work, and transportation-related activities. IPAQ-sf classifies a total combined weekly physical activity score represented as high, moderate, or low activity. |
| Patient-Focused Outcome - Dietary status will be evaluated | 32 weeks | Block 2005 Food Frequency Questionnaire (FFQ) completed at baseline, week 12 and 12 weeks post treatment to assess dietary intake. |
| Patient-focused outcome - Quality of life measure will be evaluated | 32 weeks | EuroQol 5-Dimensional (EQ-5D) questionnaire completed at weeks -4, Baseline, 4, 12 and 12 weeks post treatment to allow for assessment of quality-of-life through quality-adjusted life year (QALY) calculation |
| Measures of metabolic function (insulin) will be assessed over the duration of the study | 32 weeks | Serial measurement of insulin at Baseline, week 4, week 12, and 12 weeks post treatment |
| Measures of metabolic function (lipokine) will be assessed over the duration of the study | 32 weeks | Serial measurement of lipokine at Baseline, week 4, week 12, and 12 weeks post treatment |
| Measures of fibrosis will be assessed over the duration of the study. | 32 weeks | Serial Fibroscan assessment at screening, week 12 of Ledipasvir/Sofosbuvir (LDV/SOF) dosing, and 12 weeks after HCV treatment. |
| Measures of serial cellular immune will be assessed over the duration of the study. | 32 weeks | CD4 cell counts at Baseline, week 4, week 12, and 12 weeks post treatment |
Countries
Canada
Outcome results
None listed