Clinical trial NCT01034917: Switching From Protease Inhibitor (PI) to Etravirine in HIV-1 Infected Subjects With Viremia Suppression
Official title: Pilot Study to Assess the Efficacy and Safety of Switching Protease Inhibitor to Etravirine in HIV-1-infected Subjects With Viremia Suppression
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV
Keywords: Active Comparator
Placebo Comparator
Sham Comparator
No intervention
Other
Treatment Experienced
Lead sponsor: Germans Trias i Pujol Hospital
Sponsor class: OTHER
First posted: 2009-12-18
Enrollment: 43
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Viral load
timeFrame: week 48 after baseline
Secondary outcomes:
measure: CD4+/CD8+ T lymphocytes count
timeFrame: evolution from baseline to week 48
measure: Genotypic test
timeFrame: if virologic failure occurs
measure: Lipid profile: total, HDL-, LDL-cholesterol and triglyceride levels
timeFrame: evolution from baseline to week 48
measure: Administration of lipid-lowering drugs throughout the study
timeFrame: from baseline to week 48
measure: Cardiovascular risk assessed by the SCORE equation
timeFrame: evolution from baseline to week 48
measure: Patient's satisfaction assessed by 2 scales of type Likert
timeFrame: evolution from baseline to week 48
measure: Adverse events related to antiretroviral treatment
timeFrame: from baseline to week 48
measure: Etravirine plasma trough concentration
timeFrame: Week 4
Other outcomes:
Locations:
city: Badalona
country: Spain
facility: Germans Trias i Pujol University Hospital
state: Barcelona
Study officials:
affiliation: Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia
name: Eugenia Negredo, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.