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

• 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, W48 ] [ 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: From Baseline to W48 ] [ Designated as safety issue: No ]
• HIV-1 RNA below 50 copies/mL at 48 weeks. [ Time Frame: W48 ] [ Designated as safety issue: No ]
• Change in the lymphocyte activation marker HLADR+CD38+ from baseline to week 48. [ Time Frame: BL, W4, W12, W24, W48, W60, W72 ] [ Designated as safety issue: No ]
• Relationship between maraviroc and/or raltegravir plasma concentrations and change in the slope of decay of integrated viral DNA in PBMCs [ Time Frame: W12, W24, W48 ] [ Designated as safety issue: No ]
• HIV-1 specific CTL responses [ Time Frame: BL, W24, W48, W60, W72 ] [ Designated as safety issue: No ]
• Plasmatic inflammation biomarkers [ Time Frame: BL, W2, W4, W12, W48, W60 ] [ Designated as safety issue: No ]
• RNA, DNA and viral p24 associated to cells in ileum biopsy and PBMC [ Time Frame: W48 ] [ Designated as safety issue: No ]
• Lymphocyte activation marker HLADR+CD38+ in ileum biopsy and PBMC [ Time Frame: W48 ] [ Designated as safety issue: No ]
• Fibrosis markers in ileum biopsy and PBMC [ Time Frame: W48 ] [ Designated as safety issue: No ]

• 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 ]

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.

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.

• 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

• Experimental: 1
  From Baseline to Week48: Raltegravir BID + Tenofovir/Emtricitabine QD + Maraviroc BID From W48 to W72: Raltegravir BID + Tenofovir/Emtricitabine QD
  Interventions:

  • Drug: Raltegravir
  • Drug: Maraviroc
  • Drug: Tenofovir/Emtricitabine
• Active Comparator: 2
  Start ARV treatment with : Raltegravir BID + Tenofovir/Emtricitabine
  Interventions:

  • Drug: Raltegravir
  • Drug: Tenofovir/Emtricitabine

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.