Switching From Protease Inhibitor (PI) to Etravirine in HIV-1 Infected Subjects With Viremia Suppression

Pilot Study to Assess the Efficacy and Safety of Switching Protease Inhibitor to Etravirine in HIV-1-infected Subjects With Viremia Suppression

This is a 48 week randomized, prospective, controlled, open-label, proof-of-concept pilot clinical trial.

Patients with HIV-1 infection on HAART PI-based regimen will be randomized to switch from the PI to etravirine (400 mg dissolved in water every 24 hours) or to continue with the same approach.

The aim of the study is to compare the virological efficacy of the etravirine-based regimen with standard PI-containing regimen.

Study Overview

• Status: Completed
• Conditions: HIV
• Intervention / Treatment: Drug: Etravirine 400 mg dissolved in water every 24 hours; Drug: Continue with the same antiretroviral regimen

Detailed Description

Etravirine is a second generation non-nucleoside analogue reverse transcriptase inhibitor (NNRTI) approved by the U.S. Food and Drug Administration (FDA) in January 2008 and by the European Medicines Agency in September 2008 for clinical use in adults with incomplete virologic suppression and resistance to previous NNRTI and other antiretroviral classes.

A question that has not been explored is whether subjects with sustained undetectable HIV-1 RNA-levels experiencing antiretroviral-related toxicity can safely switch their current PI to etravirine. This treatment strategy could allow improvements in tolerability and lipid profile and would permit an easy posology (400 mg dissolved in water every 24 hours). We designed a proof-of-concept study to test the efficacy and safety of switching from a Protease Inhibitor (PI) to etravirine in subjects with viral suppression as an antiretroviral strategy of simplification therapy, based on the high antiviral potency, low toxicity, together with its easy posology (in water dissolution).

Patients with HIV-1 infection on HAART PI-based regimen will be randomized to switch from the PI to etravirine (400 mg dissolved in water every 24 hours) or to continue with the same approach.

The primary endpoint would be the percentage of patients who maintain virological suppression at week 48.

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Phase 3

Contacts and Locations

Study Locations

• Spain
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Germans Trias i Pujol University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Adult patient having a diagnosis of HIV-1 infection.
2. Antiretroviral therapy started at least 12 months before, always with a HAART combination including 2 NRTIs plus a PI.
3. Maintained undetectable plasma HIV-1 RNA (VL < 50 copies/mL) since the beginning of antiretroviral therapy, for at least 6 months.
4. Absence of suspected or documented resistance mutations in the RT associated to NNRTIs or to any NRTI.

5. Patient having at least one of the following conditions:

   • Dyslipemia (LDL cholesterol >130 mg/dL or triglycerides > 350 mg/dL) derived from their current PI regimen or current use of lipid-lowering agents due to dyslipemia,
   • Antiretroviral-related gastrointestinal disturbances, or
   • Low patient's satisfaction associated with the current regimen posology (BID regimen, ritonavir use, ritonavir intolerance…).
6. Good treatment adherence.
7. Voluntary written informed consent.

Exclusion Criteria:

1. Previous therapy with mono or dual antiretroviral therapies after initial of HAART era.
2. Previous antiretroviral treatment failures, treatment interruptions (A) or blips (B) in viral load (VL > 50 copies/mL).
3. Acute infections or uncontrolled chronic infection in the 2 months previous to the inclusion.
4. Pregnancy or fertile women willing to be pregnant.
5. Clinically significant malabsorption syndrome within 30 days prior to randomization.

(A) Patients who in the past made any interruption of treatment (provide that it has not been in the last year) may be considered candidates for the study, if they meet other criteria for inclusion, since the break in the treatment should not assume the emergence of mutations.

(B) Small blips that are preceded or forwarded by 2 undetectable viral loads will not be taken in care.

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: Etravirine group; To switch from the PI to Etravirine 400 mg dissolved in water every 24 hours	Drug: Etravirine 400 mg dissolved in water every 24 hours; Switch from the PI to Etravirine 400 mg dissolved in water every 24 hours; Other Names: ETV
Active Comparator: Control group; Continue with the same antiretroviral regimen	Drug: Continue with the same antiretroviral regimen; Continue with the same antiretroviral regimen; Other Names: CNT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Viral load	week 48 after baseline

Secondary Outcome Measures

Outcome Measure	Time Frame
CD4+/CD8+ T lymphocytes count	evolution from baseline to week 48
Genotypic test	if virologic failure occurs
Lipid profile: total, HDL-, LDL-cholesterol and triglyceride levels	evolution from baseline to week 48
Administration of lipid-lowering drugs throughout the study	from baseline to week 48
Cardiovascular risk assessed by the SCORE equation	evolution from baseline to week 48
Patient's satisfaction assessed by 2 scales of type Likert	evolution from baseline to week 48
Adverse events related to antiretroviral treatment	from baseline to week 48
Etravirine plasma trough concentration	Week 4

Collaborators and Investigators

• Sponsor: Germans Trias i Pujol Hospital
• Investigators: Principal Investigator: Eugenia Negredo, MD,PhD, Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia

Publications and helpful links

General Publications

• Echeverria P, Bonjoch A, Puig J, Molto J, Paredes R, Sirera G, Ornelas A, Perez-Alvarez N, Clotet B, Negredo E. Randomised study to assess the efficacy and safety of once-daily etravirine-based regimen as a switching strategy in HIV-infected patients receiving a protease inhibitor-containing regimen. Etraswitch study. PLoS One. 2014 Feb 4;9(2):e84676. doi: 10.1371/journal.pone.0084676. eCollection 2014.

Study record dates

Study Major Dates

• Study Start: December 1, 2009
• Primary Completion (Actual): December 1, 2011
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: December 17, 2009
• First Submitted That Met QC Criteria: December 17, 2009
• First Posted (Estimate): December 18, 2009

Study Record Updates

• Last Update Posted (Actual): January 31, 2020
• Last Update Submitted That Met QC Criteria: January 30, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: Treatment Experienced; Active Comparator; Placebo Comparator; Sham Comparator; No intervention; Other
• Additional Relevant MeSH Terms: Pathologic Processes; Virus Diseases; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Viremia; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Etravirine; Anti-Retroviral Agents
• Other Study ID Numbers: ETRA-SWITCH