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

Phase 3

Completed

• Conditions: HIV Infections
• Interventions: Drug: Raltegravir; Drug: Tenofovir/Emtricitabine; Drug: Maraviroc

• Registration Number: NCT00808002
• Lead Sponsor: Germans Trias i Pujol Hospital

Brief 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.

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.

Study Timeline

• Study First Submitted: 2008-12-12
• Study First Submitted QC: 2008-12-12
• Study First Posted: 2008-12-15
• Study Start: 2009-02
• Primary Completion: 2011-11
• Study Completion: 2011-11
• Status Verified: 2020-01
• Last Update Submitted: 2020-01-30
• Last Update Posted: 2020-01-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
2	Tenofovir/Emtricitabine	Start ARV treatment with : Raltegravir BID + Tenofovir/Emtricitabine
1	Tenofovir/Emtricitabine	From Baseline to Week48: Raltegravir BID + Tenofovir/Emtricitabine QD + Maraviroc BID From W48 to W72: Raltegravir BID + Tenofovir/Emtricitabine QD
2	Raltegravir	Start ARV treatment with : Raltegravir BID + Tenofovir/Emtricitabine
1	Maraviroc	From Baseline to Week48: Raltegravir BID + Tenofovir/Emtricitabine QD + Maraviroc BID From W48 to W72: Raltegravir BID + Tenofovir/Emtricitabine QD
1	Raltegravir	From Baseline to Week48: Raltegravir BID + Tenofovir/Emtricitabine QD + Maraviroc BID From W48 to W72: Raltegravir BID + Tenofovir/Emtricitabine QD

Primary Outcome Measures

Name	Time	Method
Change at 48 weeks in the slope of decay of integrated and unintegrated viral DNA in PBMCs.	BL, W2, W4, W12, W24, W48

Secondary Outcome Measures

Name	Time	Method
Plasmatic inflammation biomarkers	BL, W2, W4, W12, W48, W60
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
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
Relationship between maraviroc and/or raltegravir plasma concentrations and change in the slope of decay of integrated viral DNA in PBMCs	W12, W24, W48
HIV-1 specific CTL responses	BL, W24, W48, W60, W72
HIV-1 RNA below 50 copies/mL at 48 weeks.	W48
Fibrosis markers in ileum biopsy and PBMC	W48
Change in the lymphocyte activation marker HLADR+CD38+ from baseline to week 48.	BL, W4, W12, W24, W48, W60, W72
RNA, DNA and viral p24 associated to cells in ileum biopsy and PBMC	W48
Lymphocyte activation marker HLADR+CD38+ in ileum biopsy and PBMC	W48

Trial Locations

Locations (2)

Hospital Germans Trias i Pujol; 🇪🇸 Badalona, Barcelona, Spain

Hospital Clinic i Provincial de Barcelona; 🇪🇸 Barcelona, Spain