Elvitegravir/Cobicistat/Tenofovir DF/Emtricitabine With Darunavir Treatment Simplification Strategy (QuaDar)

Elvitegravir/Cobicistat/Tenofovir DF/Emtricitabine With Darunavir in Treatment-experienced Patients: Quality Control Monitoring of a Treatment Simplification Strategy

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 Overview

• Status: Completed
• Conditions: HIV Infection
• Intervention / Treatment: Drug: Treatment simplification

Detailed Description

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:

1. Complete physical exam including height and weight at baseline; symptom-directed physical exam and weight at other visits
2. Adverse clinical events including serious adverse events (hospitalizations etc.) and medication changes at every visit.
3. HIV RNA every 4 weeks.
4. CD4 and CD8 absolute counts and % at all visits except week 2.
5. Platelet count, aspartate amino transferase (AST), creatinine, estimated glomerular filtration rate (eGFR), phosphorus, urinalysis, and urine albumin to creatinine ratio (UACR) at each visit.
6. Fasting lipids (total, HDL, and LDL cholesterol and triglycerides), apolipoprotein B, high-sensitivity C- reactive protein (hsCRP) at baseline, week 24, and week 48.
7. 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.
8. 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.
9. 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.
10. Peripheral blood mononuclear cells (PBMCs) will be collected and stored at baseline for possible future study-related testing.
11. 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).

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 1Y6
      • St. Paul's Hospital Immunodeficiency Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• HIV positive adults > or = 19 years of age
• receiving stable therapy including one or two nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), in conjunction with a once-daily protease inhibitor (PI) (atazanavir, lopinavir or darunavir) and twice daily raltegravir or once daily dolutegravir
• Virologic suppression for >6 months, defined as plasma viral load (VL) consistently < 200 copies/mL with no evidence of prior virologic rebound (VL > 1000 copies/mL) on the NRTI/PI/Raltegravir regimen, AND VL < 50 copies/mL at time of study screening
• Estimated glomerular filtration rate (eGFR) > o r= 70mL/min at screening

Exclusion Criteria:

• Prior documented viral rebound > 1000 copies/mL on any raltegravir-containing regimen
• Evidence of resistance mutations compromising raltegravir or elvitegravir activity on prior genotypes.
• Evidence of clinically significant resistance to tenofovir on any previous genotype tests: K65R mutation, or 3 or more thymidine-analogue associated mutations (TAMS) compromising tenofovir activity
• Evidence of resistance mutations significantly compromising darunavir activity on any previous genotypic tests
• Current use of any nonnucleoside reverse transcriptase inhibitor (NNRTI)
• Pregnancy or breast-feeding
• Contraindications to tenofovir/FTC, elvitegravir, or cobicistat (e.g. previous significant toxicity, intolerance or drug interactions

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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 Names: Darunavir 800mg plus Stribild tablet once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma HIV RNA	Proportion of individuals with plasma HIV RNA <200copies/mL at 12 weeks following regimen switch	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
plasma HIV RNA	Proportion of individuals with plasma HIV RNA < 50 copies/mL at weeks 12, 24 and 48 post switch	weeks 12, 24 and 48
plasma HIV RNA	Proportion of individuals with plasma HIV RNA < 200 copies/mL at week 24 and 48 post switch	week 24 and 48
CD4 cell count, CD4% and CD4/CD8 ratio	Change in CD4 cell count, CD4% and CD4/CD8 ratio from study baseline to 12, 24 and 48 weeks after switch.	12, 24 and 48 weeks
serum creatinine and estimated glomerular filtration rate (eGFR)	Change in serum creatinine and eGFR from baseline to 12, 24 weeks and 48 weeks.	12, 24, and 48 weeks
Adverse event discontinuations	Proportion of adverse events experienced necessitating switch to original regimen	48 weeks
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)	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.	24 and 48 weeks
Darunavir plasma concentration	Change in darunavir trough concentration from baseline to week 2 for individuals receiving darunavir at baseline	week 2
HIV Treatment Satisfaction Questionnaire (HIVTSQ) scores and quality of life indicators (MOS-HIV scores)	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.	weeks 24 and 48
Adherence	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).	24 and 48 weeks
Elvitegravir plasma concentrations	Elvitegravir concentrations will be measured at day 14	Day 14
Adverse events	Adverse events necessitating a resumption of the previous antiretroviral regimen, and all serious adverse events will be recorded.	48 weeks

Collaborators and Investigators

• Sponsor: University of British Columbia
• Collaborators: Gilead Sciences

Publications and helpful links

General Publications

• Harris M, Ganase B, Watson B, Harrigan PR, Montaner JSG, Hull MW. HIV treatment simplification to elvitegravir/cobicistat/emtricitabine/tenofovir disproxil fumarate (E/C/F/TDF) plus darunavir: a pharmacokinetic study. AIDS Res Ther. 2017 Nov 2;14(1):59. doi: 10.1186/s12981-017-0185-4.

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (Actual): February 14, 2017
• Study Completion (Actual): February 14, 2017

Study Registration Dates

• First Submitted: July 22, 2014
• First Submitted That Met QC Criteria: July 22, 2014
• First Posted (Estimate): July 24, 2014

Study Record Updates

• Last Update Posted (Actual): November 6, 2017
• Last Update Submitted That Met QC Criteria: November 1, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: HIV; antiretroviral therapy
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Darunavir
• Other Study ID Numbers: H14-00490 (Other Identifier: UBC Providence Health Care Research Ethics Board)