Effect Of An Integrase Inhibitor On The Latency And Reservoir Of HIV-1

This study has been completed.
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal
ClinicalTrials.gov Identifier:
NCT00807443
First received: December 11, 2008
Last updated: January 31, 2013
Last verified: January 2013
  Purpose

The presence of a pool of cells latently infected by HIV-1 in patients taking HAART and with a viral load below 50 copies/mL is the main limitation to eradication of the virus from the body. This viral reservoir prevents antiretroviral therapy from being interrupted; therefore, patients are obliged to continue with treatment for a period calculated to be greater than 60 years.

Despite the important advances in knowledge of the biology of this reservoir, we still have no real knowledge about its dynamics. The opportunity to carry out a clinical trial for the first time with an integrase inhibitor is exceptional, since the results could provide important information on the nature of this reservoir.

If maintenance of the reservoir is a dynamic process, inclusion of an integrase inhibitor is expected to lead to a reduction in the size of this reservoir. This effect could be critical when including IAT (viral reactivation), since, in theory, it would be necessary to act on a smaller reservoir. Current consensus is that it would be necessary to act on almost 100% of the viral reservoir (approximately 1,000,000 cells).

The study has also been designed to enable us to understand the biochemical and molecular mechanisms by which certain drugs can induce viral reactivation in vitro as a previous step to a clinical trial aimed at reactivating viral latency and eradicating HIV-1 from the body.


Condition Intervention Phase
HIV-1
HIV Infections
Drug: Raltegravir
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Pilot Study Of The Effect Of An Integrase Inhibitor On The Latency And Reservoir Of HIV-1 In Patients Taking Highly Active Antiretroviral Therapy

Resource links provided by NLM:


Further study details as provided by Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal:

Primary Outcome Measures:
  • To evaluate, by means of a clinical trial, the effect of therapy with an integrase inhibitor (Raltegravir) on the cell reservoir of HIV-1 on patients taking HAART [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Enrollment: 10
Study Start Date: September 2009
Study Completion Date: December 2011
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Raltegravir Drug: Raltegravir
Raltegravir (INN), 400 mg tablets, developed and supplied by Merck Sharp & Dohme. A dose of 400 mg will be administered every 12 hours

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • After receiving information on the design and objectives of the study, the possible risks involved, and the fact that they can refuse to collaborate at any time, patients will give their informed consent to participate in the study and agree to provide material for the cellular and molecular studies.
  • Aged over 18 years.
  • Chronic HIV infection
  • Antiretroviral therapy with at least 3 drugs for at least 2 years and with no modifications expected during the study. Antiretroviral drugs can be switched due to intolerance as long as plasma viremia remains controlled.
  • Undetectable viral load determined by ultrasensitive techniques (<50 copies HIV RNA/mL) for at least 2 years.
  • CD4+ T lymphocyte count above 350 cells/mm3.
  • Understand the objective of the study and be available to make frequent visits to the hospital.

Exclusion Criteria:

  • Previous failure of antiretroviral therapy, understood as a rebound in viral load that can be detected after having reached undetectable levels. Low-grade increases (<200 copies of HIV RNA/mL) and transitory increases (blips) resolved without modifying antiretroviral therapy are excluded.
  • Proven resistance against the antiretroviral drugs under study.
  • Planned interruption of antiretroviral therapy.
  • Taking immunosuppressive or immunostimulating medication of any type, including valproic acid.
  • Taking a fusion inhibitor (enfuvirtide).
  • Pregnancy or intention to become pregnant during the study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00807443

Locations
Spain
Hospital Universitario Ramon Y Cajal
Madrid, Spain, 28034
Sponsors and Collaborators
Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Santiago Moreno Guillen, MD,PhD HOSPITAL UNIVERSITARIO RAMON Y CAJAL. MADRID
  More Information

No publications provided by Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal
ClinicalTrials.gov Identifier: NCT00807443     History of Changes
Other Study ID Numbers: ERRADVIH-02
Study First Received: December 11, 2008
Last Updated: January 31, 2013
Health Authority: Spain: Spanish Agency of Medicines

Keywords provided by Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal:
HIV-1
integrase inhibitor (raltegravir)
the cell reservoir of HIV-1
treatment experienced

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Integrase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 24, 2014