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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: Raltegravir
* Drug: Maraviroc
* Drug: Tenofovir/Emtricitabine


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>From Baseline to Week48: Raltegravir BID + Tenofovir/Emtricitabine QD + Maraviroc BID From W48 to W72: Raltegravir BID + Tenofovir/Emtricitabine QD | Drug: Raltegravir<br>* Raltegravir 400 mg every 12 hours<br>Drug: Maraviroc<br>* Maraviroc 300 mg every 12 hours<br>Drug: Tenofovir/Emtricitabine<br>* Tenofovir/Emtricitabine 300/200 mg every 24 hours<br>|
| Active Comparator: 2<br>Start ARV treatment with : Raltegravir BID + Tenofovir/Emtricitabine | Drug: Raltegravir<br>* Raltegravir 400 mg every 12 hours<br>Drug: Tenofovir/Emtricitabine<br>* Tenofovir/Emtricitabine 300/200 mg every 24 hours<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Maraviroc, CCR5 antagonists, Primary HIV Infection, HIV-1 reservoir, eradication, treatment naive