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

Sponsor:	Germans Trias i Pujol Hospital
Information provided by:	Germans Trias i Pujol Hospital
ClinicalTrials.gov Identifier:	NCT00808002

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 HIV Infections	Drug: Raltegravir Drug: Maraviroc Drug: Tenofovir/Emtricitabine	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
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: AIDS

Drug Information available for: Tenofovir Tenofovir disoproxil Tenofovir Disoproxil Fumarate Maraviroc Raltegravir

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 ] [ 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, W24, W48 ] [ 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 ]

Estimated Enrollment:	26
Study Start Date:	February 2009
Estimated Study Completion Date:	January 2011
Estimated Primary Completion Date:	January 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Start ARV treatment with : Raltegravir BID + Tenofovir/Emtricitabine QD + Maraviroc	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
2: Active Comparator 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:

HIV-1 infected adults (>=18 years old).
No previous antiretroviral therapy for more than 2 weeks.
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.
CCR5-tropism confirmed at screening.
Voluntary written informed consent.

Exclusion Criteria:

Pregnancy or fertile women willing to be pregnant.
Active substance abuse or major psychiatric disease.
Presence of NRTI mutations in the screening genotype.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00808002

Contacts

Contact: Bonaventura Clotet, MD,PhD

0034934978887

bclotet@flsida.org

Locations

Spain
Hospital Clinic i Provincial de Barcelona	Recruiting
Barcelona, Spain, 08916
Principal Investigator: Josep Mª Miró, MD,PhD
Spain, Barcelona
Hospital Germans Trias i Pujol	Recruiting
Badalona, Barcelona, Spain, 08916
Principal Investigator: Bonaventura Clotet, MD,PhD

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:	Lluita Sida Foundation ( Fundació LLuita contra la SIDA )
Study ID Numbers:	MARAVIBOOST
Study First Received:	December 12, 2008
Last Updated:	December 4, 2009
ClinicalTrials.gov Identifier:	NCT00808002 History of Changes
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:

Communicable Diseases
Anti-Infective Agents
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Molecular Mechanisms of Pharmacological Action
Infection
Reverse Transcriptase Inhibitors
Emtricitabine
Anti-Retroviral Agents
Therapeutic Uses
Tenofovir
Retroviridae Infections
Nucleic Acid Synthesis Inhibitors

Tenofovir disoproxil
RNA Virus Infections
Anti-HIV Agents
Immune System Diseases
Acquired Immunodeficiency Syndrome
Enzyme Inhibitors
Antiviral Agents
Immunologic Deficiency Syndromes
Pharmacologic Actions
Virus Diseases
HIV Infections
Sexually Transmitted Diseases
Lentivirus Infections

ClinicalTrials.gov processed this record on February 08, 2010