Clinical trial NCT00808002: Efficacy of Treatment Intensification With Maraviroc on HIV-1 Viral Latency in Recently Infected Hiv-1 naïve Patients Starting Raltegravir Plus Tenofovir/Emtricitabine
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV Infections
Keywords: Maraviroc
CCR5 antagonists
Primary HIV Infection
HIV-1 reservoir
eradication
treatment naive
Lead sponsor: Germans Trias i Pujol Hospital
Sponsor class: OTHER
First posted: 2008-12-15
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change at 48 weeks in the slope of decay of integrated and unintegrated viral DNA in PBMCs.
timeFrame: BL, W2, W4, W12, W24, W48
Secondary outcomes:
measure: 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.
timeFrame: BL, W2, W4, W8, W12, W24, W36, W48
measure: Blips during the study (viral load >50 copies/mL, preceded and followed by determinations <50 copies/mL in previous and posterior controls).
timeFrame: From Baseline to W48
measure: HIV-1 RNA below 50 copies/mL at 48 weeks.
timeFrame: W48
measure: Change in the lymphocyte activation marker HLADR+CD38+ from baseline to week 48.
timeFrame: BL, W4, W12, W24, W48, W60, W72
measure: Relationship between maraviroc and/or raltegravir plasma concentrations and change in the slope of decay of integrated viral DNA in PBMCs
timeFrame: W12, W24, W48
measure: HIV-1 specific CTL responses
timeFrame: BL, W24, W48, W60, W72
measure: Plasmatic inflammation biomarkers
timeFrame: BL, W2, W4, W12, W48, W60
measure: RNA, DNA and viral p24 associated to cells in ileum biopsy and PBMC
timeFrame: W48
measure: Lymphocyte activation marker HLADR+CD38+ in ileum biopsy and PBMC
timeFrame: W48
measure: Fibrosis markers in ileum biopsy and PBMC
timeFrame: W48
Other outcomes:
Locations:
city: Badalona
country: Spain
facility: Hospital Germans Trias i Pujol
state: Barcelona
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial de Barcelona
Study officials:
affiliation: LLuita contra la SIDA Foundation-HIV Unit
name: Bonaventura Clotet, MD,PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: LLuita contra la SIDA Foundation-HIV Unit
name: Josep Mª Llibre, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References: