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Efficacy of Treatment Intensification With Maraviroc on HIV-1 Viral Latency in Recently Infected Hiv-1 naïve Patients Starting Raltegravir Plus Tenofovir/Emtricitabine

The recruitment status of this study is unknown because the information has not been verified recently.
Verified January 2011 by Germans Trias i Pujol Hospital.
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by:
Germans Trias i Pujol Hospital
ClinicalTrials.gov Identifier:
NCT00808002
First received: December 12, 2008
Last updated: January 26, 2011
Last verified: January 2011
History of Changes
  Purpose

The intensification with maraviroc in recently HIV-1-infected patients of a preferred gold-standard triple therapy composed of raltegravir plus tenofovir/emtricitabine could accelerate the decay of the HIV-1 reservoir in latently infected cells established early in HIV-1 infection.

This could provide further insight into this area, decrease the size of latent reservoir, and translate into clinical benefits for patients.


Condition Intervention Phase
HIV Infections
 Drug: Raltegravir
Drug: Maraviroc
Drug: Tenofovir/Emtricitabine
 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Efficacy of Treatment Intensification With Maraviroc on HIV-1 Viral Latency in Recently Infected Hiv-1 naïve Patients Starting Raltegravir Plus Tenofovir/Emtricitabine.

Resource links provided by NLM:

MedlinePlus related topics: HIV/AIDS
U.S. FDA Resources

Further study details as provided by Germans Trias i Pujol Hospital:

Primary Outcome Measures:
  • Change at 48 weeks in the slope of decay of integrated and unintegrated viral DNA in PBMCs. [ Time Frame: BL, W2, W4, W12, W24, W48 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Decay of residual HIV-1 replication under maraviroc intensification assessed by an ultrasensitive RT-PCR assay with a lower limit of quantification of 5 copies/mL. [ Time Frame: BL, W2, W4, W8, W12, W24, W36, W48 ] [ Designated as safety issue: No ]
  • Blips during the study (viral load >50 copies/mL, preceded and followed by determinations <50 copies/mL in previous and posterior controls). [ Time Frame: From Baseline to W48 ] [ Designated as safety issue: No ]
  • HIV-1 RNA below 50 copies/mL at 48 weeks. [ Time Frame: W48 ] [ Designated as safety issue: No ]
  • Change in the lymphocyte activation marker HLADR+CD38+ from baseline to week 48. [ Time Frame: BL, W4, W12, W24, W48, W60, W72 ] [ Designated as safety issue: No ]
  • Relationship between maraviroc and/or raltegravir plasma concentrations and change in the slope of decay of integrated viral DNA in PBMCs [ Time Frame: W12, W24, W48 ] [ Designated as safety issue: No ]
  • HIV-1 specific CTL responses [ Time Frame: BL, W24, W48, W60, W72 ] [ Designated as safety issue: No ]
  • Plasmatic inflammation biomarkers [ Time Frame: BL, W2, W4, W12, W48, W60 ] [ Designated as safety issue: No ]
  • RNA, DNA and viral p24 associated to cells in ileum biopsy and PBMC [ Time Frame: W48 ] [ Designated as safety issue: No ]
  • Lymphocyte activation marker HLADR+CD38+ in ileum biopsy and PBMC [ Time Frame: W48 ] [ Designated as safety issue: No ]
  • Fibrosis markers in ileum biopsy and PBMC [ Time Frame: W48 ] [ Designated as safety issue: No ]

Estimated Enrollment: 26
Study Start Date: February 2009
Estimated Study Completion Date: May 2012
Estimated Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
From Baseline to Week48: Raltegravir BID + Tenofovir/Emtricitabine QD + Maraviroc BID From W48 to W72: Raltegravir BID + Tenofovir/Emtricitabine QD
 Drug: Raltegravir
Raltegravir 400 mg every 12 hours
Drug: Maraviroc
Maraviroc 300 mg every 12 hours
Drug: Tenofovir/Emtricitabine
Tenofovir/Emtricitabine 300/200 mg every 24 hours
Active Comparator: 2
Start ARV treatment with : Raltegravir BID + Tenofovir/Emtricitabine
 Drug: Raltegravir
Raltegravir 400 mg every 12 hours
Drug: Tenofovir/Emtricitabine
Tenofovir/Emtricitabine 300/200 mg every 24 hours

Detailed Description:

A reservoir of latently infected cells established early in infection may be involved in the maintenance of viral persistence despite continuous highly active antiretroviral therapy (HAART). This is likely to represent the major barrier to virus eradication in patients on successful combination antiretroviral therapy.

The majority of the viruses in the latent reservoir use CCR5 receptor during entry.

More recently, clear evidences for decay of this HIV-1 reservoir in patients who initiated antiretroviral therapy early in infection have been demonstrated. The treatment of acute infection may set the stage for subsequent attempts at eradication. To achieve this, more potent antiretroviral therapy and/or more potent antilatency therapies may be needed.

In contrast to previous antiretroviral drugs, maraviroc does not need to cross the cell membrane, nor does not require intracellular processing in order to exert its activity. In addition, there is no cross-resistance between entry inhibitors and agents that act on intracellular targets.

Maraviroc has demonstrated potent antiviral activity against all CCR5-tropic HIV-1 viruses tested. Maraviroc could thus fulfil the requirements for an optimal candidate for treatment intensification in HIV-1 infected patients with a recent HIV-1 infection.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. HIV-1 infected adults (>=18 years old).
  2. No previous antiretroviral therapy for more than 2 weeks.
  3. HIV-1 infection documented in the past 6 months by a previous negative ELISA test, or a documented clinical acute seroconversion in the past 6 months.
  4. CCR5-tropism confirmed at screening.
  5. Voluntary written informed consent.

Exclusion Criteria:

  1. Pregnancy or fertile women willing to be pregnant.
  2. Active substance abuse or major psychiatric disease.
  3. Presence of NRTI mutations in the screening genotype.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00808002

Locations
Spain
Hospital Germans Trias i Pujol
Badalona, Barcelona, Spain, 08916
Hospital Clinic i Provincial de Barcelona
Barcelona, Spain, 08916
Sponsors and Collaborators
Germans Trias i Pujol Hospital
Investigators
Principal Investigator: Bonaventura Clotet, MD,PhD LLuita contra la SIDA Foundation-HIV Unit
Principal Investigator: Josep Mª Llibre, MD,PhD LLuita contra la SIDA Foundation-HIV Unit
  More Information

No publications provided

Responsible Party: Fundació LLuita contra la SIDA, Lluita Sida Foundation
ClinicalTrials.gov Identifier: NCT00808002     History of Changes
Other Study ID Numbers: MARAVIBOOST
Study First Received: December 12, 2008
Last Updated: January 26, 2011
Health Authority: Spain: Ministry of Health

Keywords provided by Germans Trias i Pujol Hospital:
Maraviroc
CCR5 antagonists
Primary HIV Infection
 HIV-1 reservoir
eradication
treatment naive

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Tenofovir
 Tenofovir disoproxil
Emtricitabine
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on May 19, 2013