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

December 12, 2008
January 26, 2011
February 2009
November 2011   (final data collection date for primary outcome measure)
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 ]
Same as current
Complete list of historical versions of study NCT00808002 on ClinicalTrials.gov Archive Site
  • 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 ]
  • 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 ] [ 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: BL, W1, W2, W4, W8, W12, W24, W36 ] [ Designated as safety issue: No ]
  • HIV-1 RNA below 50 copies/mL at 48 weeks. [ Time Frame: BL, W1, W2, W4, W8, W12, W24, W36 ] [ Designated as safety issue: No ]
  • Change in the lymphocyte activation marker HLADR+CD38+ from baseline to week 48. [ Time Frame: BL, W4, W12, W48 ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Efficacy of Treatment Intensification With Maraviroc on HIV-1 Viral Latency in Recently Infected Hiv-1 naïve Patients Starting Raltegravir Plus Tenofovir/Emtricitabine
Efficacy of Treatment Intensification With Maraviroc on HIV-1 Viral Latency in Recently Infected Hiv-1 naïve Patients Starting Raltegravir Plus Tenofovir/Emtricitabine.

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.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
HIV Infections
  • 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
  • Experimental: 1
    From Baseline to Week48: Raltegravir BID + Tenofovir/Emtricitabine QD + Maraviroc BID From W48 to W72: Raltegravir BID + Tenofovir/Emtricitabine QD
    Interventions:
    • Drug: Raltegravir
    • Drug: Maraviroc
    • Drug: Tenofovir/Emtricitabine
  • Active Comparator: 2
    Start ARV treatment with : Raltegravir BID + Tenofovir/Emtricitabine
    Interventions:
    • Drug: Raltegravir
    • Drug: Tenofovir/Emtricitabine
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
26
May 2012
November 2011   (final data collection date for primary outcome measure)

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.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Spain
 
NCT00808002
MARAVIBOOST
No
Fundació LLuita contra la SIDA, Lluita Sida Foundation
Germans Trias i Pujol Hospital
Not Provided
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
Germans Trias i Pujol Hospital
January 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP