Clinical trial NCT02199613: Elvitegravir/Cobicistat/Tenofovir DF/Emtricitabine With Darunavir Treatment Simplification Strategy
Official title: Elvitegravir/Cobicistat/Tenofovir DF/Emtricitabine With Darunavir in Treatment-experienced Patients: Quality Control Monitoring of a Treatment Simplification Strategy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: HIV Infection
Keywords: HIV
antiretroviral therapy
Lead sponsor: University of British Columbia
Sponsor class: OTHER
Collaborators: name: Gilead Sciences
First posted: 2014-07-24
Enrollment: 10
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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).

Eligibility criteria: 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

Primary outcomes:
measure: Plasma HIV RNA
timeFrame: 12 weeks
Secondary outcomes:
measure: plasma HIV RNA
timeFrame: weeks 12, 24 and 48
measure: plasma HIV RNA
timeFrame: week 24 and 48
measure: CD4 cell count, CD4% and CD4/CD8 ratio
timeFrame: 12, 24 and 48 weeks
measure: serum creatinine and estimated glomerular filtration rate (eGFR)
timeFrame: 12, 24, and 48 weeks
measure: Adverse event discontinuations
timeFrame: 48 weeks
measure: 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)
timeFrame: 24 and 48 weeks
measure: Darunavir plasma concentration
timeFrame: week 2
measure: HIV Treatment Satisfaction Questionnaire (HIVTSQ) scores and quality of life indicators (MOS-HIV scores)
timeFrame: weeks 24 and 48
measure: Adherence
timeFrame: 24 and 48 weeks
measure: Elvitegravir plasma concentrations
timeFrame: Day 14
measure: Adverse events
timeFrame: 48 weeks
Other outcomes:
Locations:
city: Vancouver
country: Canada
facility: St. Paul's Hospital Immunodeficiency Clinic
state: British Columbia
Study officials:
affiliation: University of British Columbia
name: Mark Hull, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.