Clinical trial NCT00966329: Switching the Non-nucleoside Reverse Transcriptase Inhibitor (NNRTI) or Protease Inhibitor (PI) to Maraviroc in HIV Subjects
Official title: Pilot Study to Assess the Safety and Efficacy of Switching the Nnrti or pi to Maraviroc in Hiv-1-infected Subjects With Persistent Viremia Suppression
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: HIV
HIV Infections
Keywords: Switching
Maraviroc
Virological efficacy
Lipid profile
Tropism
Lead sponsor: Germans Trias i Pujol Hospital
Sponsor class: OTHER
First posted: 2009-08-26
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Patients with HIV-1 infection on HAART regimen including 2 NRTI/NtRTIs plus one of the following : 1 PI/ritonavir or ATV/unboosted or 1 NNRTI, will be randomized to switch from the NNRTI/PI to maraviroc (300 mg /12 h) or to continue with the same approach.

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

Patients with HIV-1 infection on HAART regimen including 2 NRTI/NtRTIs plus one of the following : 1 PI/ritonavir (lopinavir/ritonavir, atazanavir/ritonavir, fosamprenavir /ritonavir, tipranavir/ritonavir, darunavir/ritonavir) or ATV/unboosted (in a regimen without tenofovir) or 1 NNRTI (nevirapine or efavirenz).

Patients will be randomized to switch from the NNRTI/PI to maraviroc (300 mg /12 h) 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. HIV-1 infected adults (=/+18 years old).
2. Patient having a diagnosis of HIV infection, on stable HAART including 2 NRTI/NtRTIs plus one of the following: 1 PI/ritonavir or ATV/unboosted or 1 NNRTI.
3. Undetectable plasma HIV-1 RNA (VL \< 50 copies/mL) while on HAART.
4. Patient having at least one of the following conditions:

   * Antiretroviral-related gastrointestinal disturbances, or
   * Low patient's satisfaction associated with the current regimen posology (ritonavir use, ritonavir intolerance...), or
   * Any toxicity drug related.
5. Nadir CD4 cell count \> 350 cells/mm3.
6. Absence of resistance mutations in the RT or PR by (TrugeneTM)
7. Good treatment adherence.
8. Voluntary written informed consent.

Exclusion Criteria:

1. Virologic failure to a previous antiretroviral regimen.
2. Any antiretroviral resistance mutation in a previous resistance test.
3. Dual/mixed or X4 viruses detected at any time point, including the pre-treatment ES-Trofile test of the PBMC test done before treatment switch.
4. Acute infections or uncontrolled chronic infection in the 2 months previous to the inclusion.
5. Pregnancy or fertile women willing to be pregnant.

Primary outcomes:
measure: Viral load
timeFrame: 48 weeks
Secondary outcomes:
measure: Time to virological failure
timeFrame: 48 weeks
measure: Administration of lipid-lowering drugs
timeFrame: 48 weeks
measure: Changes in the SCORE equation
timeFrame: 48 weeks
measure: CD4 / CD8 cell counts
timeFrame: 48 weeks
measure: Antiretroviral resistance and viral tropism
timeFrame: 48 weeks
measure: Patients who withdraw
timeFrame: 48 weeks
measure: Total cholesterol
timeFrame: 48 weeks
measure: HDL-cholesterol
timeFrame: 48 weeks
measure: LDL-cholesterol
timeFrame: 48 weeks
measure: Triglyceride
timeFrame: 48 weeks
Other outcomes:
Locations:
city: Badalona
country: Spain
facility: Germans Trias i Pujol Hospital
state: Barcelona
city: Badalona
country: Spain
facility: Lluita contra la Sida Foundation, HIV Unit, Irsi Caixa Foundation
state: Barcelona
city: Badalona
country: Spain
facility: Lluita contra la Sida Foundation, HIV Unit
state: Barcelona
Study officials:
affiliation: Lluita contra la Sida Foundation, HIV Unit
name: Eugènia Negredo, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bonjoch A, Pou C, Perez-Alvarez N, Bellido R, Casadella M, Puig J, Noguera-Julian M, Clotet B, Negredo E, Paredes R. Switching the third drug of antiretroviral therapy to maraviroc in aviraemic subjects: a pilot, prospective, randomized clinical trial. J Antimicrob Chemother. 2013 Jun;68(6):1382-7. doi: 10.1093/jac/dks539. Epub 2013 Jan 25.