HIV Infections
Conditions
Keywords
Maraviroc, CCR5 antagonists, Primary HIV Infection, HIV-1 reservoir, eradication, treatment naive
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.
Interventions
DRUGRaltegravir
Raltegravir 400 mg every 12 hours
DRUGMaraviroc
Maraviroc 300 mg every 12 hours
Tenofovir/Emtricitabine 300/200 mg every 24 hours
Sponsors
Germans Trias i Pujol Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| 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
| Measure | Time frame |
|---|---|
| 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 |
| 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 |
| 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 |
| HIV-1 specific CTL responses | BL, W24, W48, W60, W72 |
Countries
Spain
Outcome results
None listed