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.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Raltegravir; Drug: Maraviroc; Drug: Tenofovir/Emtricitabine

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 Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 3

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08916
    • Hospital Clinic i Provincial de Barcelona
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Hospital Germans Trias i Pujol

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; From Baseline to Week48: Raltegravir BID + Tenofovir/Emtricitabine QD + Maraviroc BID From W48 to W72: Raltegravir BID + Tenofovir/Emtricitabine QD	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
Active Comparator: 2; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Time Frame
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
HIV-1 RNA below 50 copies/mL at 48 weeks.	W48
Change in the lymphocyte activation marker HLADR+CD38+ from baseline to week 48.	BL, W4, W12, W24, W48, W60, W72
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
Plasmatic inflammation biomarkers	BL, W2, W4, W12, W48, W60
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
Fibrosis markers in ileum biopsy and PBMC	W48

Collaborators and Investigators

• Sponsor: Germans Trias i Pujol Hospital
• Investigators: Principal Investigator: Josep Mª Llibre, MD,PhD, LLuita contra la Sida Foundation-HIV Unit

Study record dates

Study Major Dates

• Study Start: February 1, 2009
• Primary Completion (Actual): November 1, 2011
• Study Completion (Actual): November 1, 2011

Study Registration Dates

• First Submitted: December 12, 2008
• First Submitted That Met QC Criteria: December 12, 2008
• First Posted (Estimate): December 15, 2008

Study Record Updates

• Last Update Posted (Actual): January 31, 2020
• Last Update Submitted That Met QC Criteria: January 30, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: Primary HIV Infection; treatment naive; CCR5 antagonists; Maraviroc; eradication; HIV-1 reservoir
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; HIV Integrase Inhibitors; Integrase Inhibitors; HIV Fusion Inhibitors; Viral Fusion Protein Inhibitors; CCR5 Receptor Antagonists; Tenofovir; Emtricitabine; Raltegravir Potassium; Maraviroc
• Other Study ID Numbers: MARAVIBOOST