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

Sponsored by:	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 BID Drug: Tenofovir/Emtricitabine	Phase III

MedlinePlus related topics: AIDS

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

U.S. FDA Resources

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.

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, W48 ] [ Designated as safety issue: No ]

Estimated Enrollment:	20
Study Start Date:	February 2009
Estimated Study Completion Date:	July 2010
Estimated Primary Completion Date:	July 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Start ARV treatment with : Raltegravir BID + Tenofovir/Emtricitabine QD + Maraviroc BID	Drug: Raltegravir Raltegravir 400 mg every 12 hours Drug: Maraviroc BID 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 QD	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
Barcelona, Spain, 08916
Spain, Barcelona
Hospital Germans Trias i Pujol
Badalona, 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

Responsible Party:	Lluita Sida Foundation ( Fundació LLuita contra la SIDA )
Study ID Numbers:	MARAVIBOOST
Study First Received:	December 12, 2008
Last Updated:	January 7, 2009
ClinicalTrials.gov Identifier:	NCT00808002
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

Study placed in the following topic categories:

Virus Diseases
Sexually Transmitted Diseases, Viral
Emtricitabine
HIV Infections
Sexually Transmitted Diseases

Acquired Immunodeficiency Syndrome
Tenofovir
Retroviridae Infections
Immunologic Deficiency Syndromes
Tenofovir disoproxil

Additional relevant MeSH terms:

Anti-Infective Agents
RNA Virus Infections
Anti-HIV Agents
Slow Virus Diseases
Immune System Diseases
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Infection

Antiviral Agents
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Anti-Retroviral Agents
Therapeutic Uses
Lentivirus Infections
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on January 14, 2009