Efficacy of Treatment Intensification With Maraviroc on HIV-1 Viral Latency in Recently Infected Hiv-1 naïve Patients Starting Raltegravir Plus Tenofovir/Emtricitabine
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|ClinicalTrials.gov Identifier: NCT00808002|
Recruitment Status : Completed
First Posted : December 15, 2008
Last Update Posted : September 8, 2014
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.
|Condition or disease||Intervention/treatment||Phase|
|HIV Infections||Drug: Raltegravir Drug: Maraviroc Drug: Tenofovir/Emtricitabine||Phase 3|
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 (Clinical Trial)|
|Actual Enrollment :||30 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|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.|
|Study Start Date :||February 2009|
|Primary Completion Date :||November 2011|
|Study Completion Date :||November 2011|
From Baseline to Week48: Raltegravir BID + Tenofovir/Emtricitabine QD + Maraviroc BID From W48 to W72: Raltegravir BID + Tenofovir/Emtricitabine QD
Raltegravir 400 mg every 12 hoursDrug: Maraviroc
Maraviroc 300 mg every 12 hoursDrug: Tenofovir/Emtricitabine
Tenofovir/Emtricitabine 300/200 mg every 24 hours
Active Comparator: 2
Start ARV treatment with : Raltegravir BID + Tenofovir/Emtricitabine
Raltegravir 400 mg every 12 hoursDrug: Tenofovir/Emtricitabine
Tenofovir/Emtricitabine 300/200 mg every 24 hours
- Change at 48 weeks in the slope of decay of integrated and unintegrated viral DNA in PBMCs. [ Time Frame: BL, W2, W4, W12, W24, W48 ]
- 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 ]
- 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 ]
- HIV-1 RNA below 50 copies/mL at 48 weeks. [ Time Frame: W48 ]
- Change in the lymphocyte activation marker HLADR+CD38+ from baseline to week 48. [ Time Frame: 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 [ Time Frame: W12, W24, W48 ]
- HIV-1 specific CTL responses [ Time Frame: BL, W24, W48, W60, W72 ]
- Plasmatic inflammation biomarkers [ Time Frame: BL, W2, W4, W12, W48, W60 ]
- RNA, DNA and viral p24 associated to cells in ileum biopsy and PBMC [ Time Frame: W48 ]
- Lymphocyte activation marker HLADR+CD38+ in ileum biopsy and PBMC [ Time Frame: W48 ]
- Fibrosis markers in ileum biopsy and PBMC [ Time Frame: W48 ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00808002
|Hospital Germans Trias i Pujol|
|Badalona, Barcelona, Spain, 08916|
|Hospital Clinic i Provincial de Barcelona|
|Barcelona, Spain, 08916|
|Principal Investigator:||Bonaventura Clotet, MD,PhD||LLuita contra la SIDA Foundation-HIV Unit|
|Principal Investigator:||Josep Mª Llibre, MD,PhD||LLuita contra la SIDA Foundation-HIV Unit|