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

HIV Infections Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00808002
• Other study ID #: MARAVIBOOST
• Status: Completed
• Phase: Phase 3
• Start date: February 2009
• Est. completion date: November 2011

Study information

• Verified date: January 2020
• Source: Germans Trias i Pujol Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: November 2011
• Est. primary completion date: November 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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.

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• Raltegravir
Raltegravir 400 mg every 12 hours
• Maraviroc
Maraviroc 300 mg every 12 hours
• Tenofovir/Emtricitabine
Tenofovir/Emtricitabine 300/200 mg every 24 hours

Locations

Country	Name	City	State
Spain	Hospital Germans Trias i Pujol	Badalona	Barcelona
Spain	Hospital Clinic i Provincial de Barcelona	Barcelona

Sponsors (1)

Lead Sponsor	Collaborator
Germans Trias i Pujol Hospital

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change at 48 weeks in the slope of decay of integrated and unintegrated viral DNA in PBMCs.		BL, W2, W4, W12, W24, W48
Secondary	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.		BL, W2, W4, W8, W12, W24, W36, W48
Secondary	Blips during the study (viral load >50 copies/mL, preceded and followed by determinations <50 copies/mL in previous and posterior controls).		From Baseline to W48
Secondary	HIV-1 RNA below 50 copies/mL at 48 weeks.		W48
Secondary	Change in the lymphocyte activation marker HLADR+CD38+ from baseline to week 48.		BL, W4, W12, W24, W48, W60, W72
Secondary	Relationship between maraviroc and/or raltegravir plasma concentrations and change in the slope of decay of integrated viral DNA in PBMCs		W12, W24, W48
Secondary	HIV-1 specific CTL responses		BL, W24, W48, W60, W72
Secondary	Plasmatic inflammation biomarkers		BL, W2, W4, W12, W48, W60
Secondary	RNA, DNA and viral p24 associated to cells in ileum biopsy and PBMC		W48
Secondary	Lymphocyte activation marker HLADR+CD38+ in ileum biopsy and PBMC		W48
Secondary	Fibrosis markers in ileum biopsy and PBMC		W48