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

NCT00807443 | Completed Phase 2

• 1 other identifier: ERRADVIH-02
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

HIV-1; HIV Infections

Keywords

HIV-1; integrase inhibitor (raltegravir); the cell reservoir of HIV-1; treatment experienced

Outcome Measures

Primary Outcomes (1)

• 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

  12 months

Study Arms (1)

Raltegravir

EXPERIMENTAL

Drug: Raltegravir

Interventions

Raltegravir DRUG

Raltegravir (INN), 400 mg tablets, developed and supplied by Merck Sharp \& Dohme. A dose of 400 mg will be administered every 12 hours

Raltegravir

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Hospital Universitario Ramon Y Cajal

Madrid, Madrid, 28034, Spain

Location

Related Publications (1)

• Serrano-Villar S, Gutierrez C, Vallejo A, Hernandez-Novoa B, Diaz L, Abad Fernandez M, Madrid N, Dronda F, Zamora J, Munoz-Fernandez MA, Moreno S. The CD4/CD8 ratio in HIV-infected subjects is independently associated with T-cell activation despite long-term viral suppression. J Infect. 2013 Jan;66(1):57-66. doi: 10.1016/j.jinf.2012.09.013. Epub 2012 Oct 6.

  PMID: 23046968 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

Raltegravir Potassium

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Santiago Moreno Guillen, MD,PhD

  HOSPITAL UNIVERSITARIO RAMON Y CAJAL. MADRID

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 11, 2008
• First Posted: December 12, 2008
• Study Start: September 1, 2009
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2011
• Last Updated: February 1, 2013

Record last verified: 2013-01

Locations

ES (1)