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Completed

NCT Number: NCT00808002

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

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.

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Key information

Age range

18 year–99 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

raltegravir

Drug

Raltegravir 400 mg every 12 hours

Maraviroc

Drug

Maraviroc 300 mg every 12 hours

Tenofovir/Emtricitabine

Drug

Tenofovir/Emtricitabine 300/200 mg every 24 hours

Primary outcomes

  1. 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

Secondary outcomes

  1. 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

  2. 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

  3. HIV-1 RNA below 50 copies/mL at 48 weeks.

    Time frame: W48

  4. Change in the lymphocyte activation marker HLADR+CD38+ from baseline to week 48.

    Time frame: BL, W4, W12, W24, W48, W60, W72

  5. 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

  6. HIV-1 specific CTL responses

    Time frame: BL, W24, W48, W60, W72

  7. Plasmatic inflammation biomarkers

    Time frame: BL, W2, W4, W12, W48, W60

  8. RNA, DNA and viral p24 associated to cells in ileum biopsy and PBMC

    Time frame: W48

  9. Lymphocyte activation marker HLADR+CD38+ in ileum biopsy and PBMC

    Time frame: W48

  10. Fibrosis markers in ileum biopsy and PBMC

    Time frame: W48

Sponsors and collaborators

Lead sponsor

Germans Trias i Pujol Hospital

Other

Registry information

Official study title

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

Important dates

Study start
2009
Primary completion
2011
Study completion
2011
First posted
Dec 15, 2008
Registry last updated
Jan 31, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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