HIV Drug Switch Followed by HCV Therapy in HIV-HCV Co-Infection
HIV Drug Switch Followed by HCV Therapy in HIV-HCV Co-Infection
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 looking into 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) 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.
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 fumerate (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.
Inclusion

 -  HIV infected (ELISA with western blot confirmation)

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

 -  Prescribed cART that may include any 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 0 - 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:

 -  Concomitant use of drugs with contraindication drug interactions with E/C/F/TAF of
 SOF-LDV

 -  History of HIV integrase inihbitors or NRTI resistance mutations

 -  Platelets <50 x109/L