Virological and Immunological Safety of a Dose Reduction Strategy Antiretroviral Regimen With Efavirenz / Tenofovir / Emtricitabine (A-TRI-WEEK)

The main objective is to determine the feasibility of maintaining virologic suppression on standard plasma viral load by dose reduction of ATRIPLA ®.

Study Overview

• Status: Completed
• Conditions: HIV
• Intervention / Treatment: Drug: ATRIPLA

Detailed Description

The main objective of this study is to determine the feasibility of maintaining virologic suppression on standard plasma viral load (limit of detection 37 copies / mL) of a dose reduction strategy of ATRIPLA ® once a day to three tablets per week in patients infected with HIV-1 with sustained suppression of plasma viral load standard for more than two years.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 4

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic i Provincial Barcelona

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adults (≥ 18 years)
• HIV-1 infection, clinical stability, and treatment with ATRIPLA ® for the past two years.
• Standard plasma viral load below the limit of detection for at least 2 years.
• CD4 count above 350/mm3 at the time of the consideration for the study.
• Negative pregnancy test in women of childbearing age, and commitment acceptable contraceptive use for at least 2 weeks before day 1 and until at least 6 months after the last dose of study drug.
• Patients should be given written informed consent
• In the opinion of the investigator, be able to follow the design of the protocol visits

Exclusion Criteria:

• Patients who have experienced virologic failure prior to any antiretroviral regimen
• Evidence of previous mutations versus efavirenz, tenofovir and emtricitabine
• Use of any other chronic treatment plus ATRIPLA has been introduced in the 6 months prior to entry of the patient in the study
• Any contraindication to study drug
• Any condition not ensure proper adherence to the study at the discretion of the attending physician of the patient
• Uncontrolled preexisting psychiatric illness
• Any current sign of alcoholism or other drug use.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ATRIPLA three times a week.; Atripla (600 mg/200 mg/245 mg) three times a week.	Drug: ATRIPLA; Other Names: efavirenz/emtricitabine/tenofovir disoproxil fumarate 600 mg/200; mg/245 mg
Active Comparator: ATRIPLA one time a day.; Atripla (600 mg/200 mg/245 mg) one time a day.	Drug: ATRIPLA; Other Names: efavirenz/emtricitabine/tenofovir disoproxil fumarate 600 mg/200; mg/245 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of patients who continue with a standard plasma viral load (<37 copies / mL) at 24 weeks by intention to treat analysis.	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of patients with ultrasensitive viral load (<1 copy / mL) after 24 weeks.		24 weeks
The change from baseline to 24 weeks in the viral reservoir in peripheral blood mononuclear cells		baseline and 6 months
Immunological	Changes from baseline to 24 weeks in the production of TRECs, the immunological profile of activation (CD38 and HLA-DR) and senescence (CD57 and CD28) in CD4 and CD8 lineages in the proportions of naive T cells effector and memory (CCR7 and CD45RA), and changes in the levels of apoptosis in vitro by staining with annexin V.	baseline and 6 months
Changes in plasma levels of efavirenz.		baseline and 6 months
Changes in sleep quality (Pittsburgh Sleep Quality Index).		baseline and 6 months
General Safety (report adverse events, serious adverse events and treatment discontinuation due to adverse events)		24 weeks
Changes in plasma levels of vitamin D.		baseline and 6 months
Changes in lipid profile.		baseline and 6 months
Changes in estimated glomerular filtration rate.		baseline and 6 months

Collaborators and Investigators

• Sponsor: Anna Cruceta
• Investigators: Principal Investigator: Esteban Martinez, MD, Hospital Clinic i Provincial de Barcelona

Publications and helpful links

General Publications

• Guardo AC, Zarama A, Gonzalez T, Bargallo ME, Rojas J, Martinez E, Plana M, Sanchez-Palomino S. Effects on immune system and viral reservoir of a short-cycle antiretroviral therapy in virologically suppressed HIV-positive patients. AIDS. 2019 May 1;33(6):965-972. doi: 10.1097/QAD.0000000000002169.
• Rojas J, Blanco JL, Sanchez-Palomino S, Marcos MA, Guardo AC, Gonzalez-Cordon A, Lonca M, Tricas A, Rodriguez A, Romero A, Miro JM, Mallolas J, Gatell JM, Plana M, Martinez E. A maintenance 3-day-per-week schedule with the single tablet regimen efavirenz/emtricitabine/tenofovir disoproxil fumarate is effective and decreases sub-clinical toxicity. AIDS. 2018 Jul 31;32(12):1633-1641. doi: 10.1097/QAD.0000000000001843.

Study record dates

Study Major Dates

• Study Start: May 1, 2013
• Primary Completion (Actual): November 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: January 18, 2013
• First Submitted That Met QC Criteria: January 25, 2013
• First Posted (Estimate): January 29, 2013

Study Record Updates

• Last Update Posted (Estimate): September 2, 2015
• Last Update Submitted That Met QC Criteria: September 1, 2015
• Last Verified: May 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Tenofovir; Emtricitabine; Efavirenz; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
• Other Study ID Numbers: A-TRI-WEEK