Elvitegravir/Cobicistat/Tenofovir DF/Emtricitabine With Darunavir Treatment Simplification Strategy (QuaDar)
The study aims to assess the safety and efficacy of darunavir 800mg plus the co-formulated elvitegravir/cobicistat/tenofovir disoproxil fumarate (DF)/emtricitabine (Stribild) tablet as a simplification strategy for the treatment of HIV infection in HIV-infected subjects who have had previous antiretroviral treatment experience with multiple-drug regimens.
We hypothesize that elvitegravir/cobicistat/tenofovir DF/emtricitabine with darunavir will offer a safe and efficacious treatment simplification strategy for HIV positive patients currently receiving multiple-drug regimens to control their HIV infection.
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Elvitegravir/Cobicistat/Tenofovir DF/Emtricitabine With Darunavir in Treatment-experienced Patients: Quality Control Monitoring of a Treatment Simplification Strategy|
- Plasma HIV RNA [ Time Frame: 12 weeks ]Proportion of individuals with plasma HIV RNA <200copies/mL at 12 weeks following regimen switch
- plasma HIV RNA [ Time Frame: weeks 12, 24 and 48 ]Proportion of individuals with plasma HIV RNA < 50 copies/mL at weeks 12, 24 and 48 post switch
- plasma HIV RNA [ Time Frame: week 24 and 48 ]Proportion of individuals with plasma HIV RNA < 200 copies/mL at week 24 and 48 post switch
- CD4 cell count, CD4% and CD4/CD8 ratio [ Time Frame: 12, 24 and 48 weeks ]Change in CD4 cell count, CD4% and CD4/CD8 ratio from study baseline to 12, 24 and 48 weeks after switch.
- serum creatinine and estimated glomerular filtration rate (eGFR) [ Time Frame: 12, 24, and 48 weeks ]Change in serum creatinine and eGFR from baseline to 12, 24 weeks and 48 weeks.
- Adverse event discontinuations [ Time Frame: 48 weeks ]Proportion of adverse events experienced necessitating switch to original regimen
- fasting lipid parameters (total cholesterol, LDL, HDL, triglycerides, and apolipoprotein B [apoB]), AST to platelet ratio index (APRI) score, and high-sensitivity C-reactive protein (hsCRP) [ Time Frame: 24 and 48 weeks ]Changes in fasting lipid parameters (total cholesterol, LDL, HDL, triglycerides, and apolipoprotein B [apoB]), AST to platelet ratio index (APRI) score, and high-sensitivity C-reactive protein (hsCRP) between baseline and 24 and 48 weeks.
- Darunavir plasma concentration [ Time Frame: week 2 ]Change in darunavir trough concentration from baseline to week 2 for individuals receiving darunavir at baseline
- HIV Treatment Satisfaction Questionnaire (HIVTSQ) scores and quality of life indicators (MOS-HIV scores) [ Time Frame: weeks 24 and 48 ]Changes in HIV Treatment Satisfaction Questionnaire (HIVTSQ) scores and quality of life indicators (MOS-HIV scores) between baseline and weeks 24 and 48 following switch.
- Adherence [ Time Frame: 24 and 48 weeks ]Changes in antiretroviral adherence from baseline to 24 and 48 weeks. Adherence will be assessed using two measures: the ACTG treatment adherence questionnaire and the Medication adherence self-report inventory (MASRI).
- Elvitegravir plasma concentrations [ Time Frame: Day 14 ]Elvitegravir concentrations will be measured at day 14
- Adverse events [ Time Frame: 48 weeks ]Adverse events necessitating a resumption of the previous antiretroviral regimen, and all serious adverse events will be recorded.
|Study Start Date:||October 2014|
|Estimated Study Completion Date:||December 2017|
|Estimated Primary Completion Date:||January 2017 (Final data collection date for primary outcome measure)|
Experimental: Treatment simplification
Open-label darunavir 800mg in conjunction with the co-formulated tenofovir DF/FTC/cobicistat/elvitegravir (Stribild) tablet, both taken together once daily with food
Drug: Treatment simplification
Eligible, consenting subjects will start open-label darunavir 800mg plus the co-formulated tenofovir DF/FTC/cobicistat/elvitegravir (Stribild) tablet once daily with food, following the study procedures at the baseline visit. They will be assessed at weeks 2, 12, 24, 36, and 48 after starting the new regimen.
Other Name: Darunavir 800mg plus Stribild tablet once daily
Eligible, consenting subjects will be assessed at baseline and weeks 2, 12, 24, 36, and 48. Study medications will be dispensed at all visits except week 2, and all participants will commence taking open-label darunavir 800mg in conjunction with the co-formulated tenofovir DF/emtricitabine/cobicistat/elvitegravir (Stribild) tablet, both taken together once daily with food, following study procedures at baseline.
Assessments at the study visits will include:
- Complete physical exam including height and weight at baseline; symptom-directed physical exam and weight at other visits
- Adverse clinical events including serious adverse events (hospitalizations etc.) and medication changes at every visit.
- HIV RNA every 4 weeks.
- CD4 and CD8 absolute counts and % at all visits except week 2.
- Platelet count, aspartate amino transferase (AST), creatinine, estimated glomerular filtration rate (eGFR), phosphorus, urinalysis, and urine albumin to creatinine ratio (UACR) at each visit.
- Fasting lipids (total, HDL, and LDL cholesterol and triglycerides), apolipoprotein B, high-sensitivity C- reactive protein (hsCRP) at baseline, week 24, and week 48.
- Pregnancy test for women of child-bearing potential (as defined above) at every visit except week 2. In addition, pregnancy tests will be performed monthly for women of child-bearing potential; between study visits these may be done at home.
- A plasma sample (3 mL) will be collected and stored once at baseline for all subjects, and used for measurement of darunavir trough (pre-dose) concentration in subjects receiving darunavir in their pre-study regimen.
- All subjects will take their study medication under observation in the clinic on Day 14, and plasma samples (3mL) for pharmacokinetic testing will be drawn immediately pre-dose and at 1, 2, 3, 4, 5, 6, and 8 hours post-dose. Subjects will return the following day before taking their Day 15 dose for a 24-hour post-dose sample.
- Peripheral blood mononuclear cells (PBMCs) will be collected and stored at baseline for possible future study-related testing.
- The following questionnaires will be completed by participants prior to other study procedures at baseline and at weeks 24 and 48: MOS-HIV quality of life questionnaire; HIVTSQ; ACTG treatment adherence questionnaire; and the medication adherence self-report inventory (MASRI).
Please refer to this study by its ClinicalTrials.gov identifier: NCT02199613
|Canada, British Columbia|
|St. Paul's Hospital Immunodeficiency Clinic|
|Vancouver, British Columbia, Canada, V6Z 1Y6|
|Principal Investigator:||Mark Hull, MD||University of British Columbia|