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Impact of MK-0518 (Raltegravir) Intensification on HIV-1 Viral Latency in Patients With Previous Complete Viral Suppression

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00554398
First Posted: November 6, 2007
Last Update Posted: November 13, 2009
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Fundacio Lluita Contra la SIDA
Information provided by:
Germans Trias i Pujol Hospital
  Purpose
An intensification with the HIV-1 integrase inhibitor Raltegravir (RAL) of a stable HAART regimen with persistent HIV-1 viral suppression could increase the slope of decay of the HIV-1 latent reservoir.

Condition Intervention Phase
HIV Infections Drug: MK-0518 400mg twice a day Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Impact of MK-0518 (Raltegravir) Intensification on HIV-1 Viral Latency in Patients With Previous Complete Viral Suppression

Resource links provided by NLM:


Further study details as provided by Germans Trias i Pujol Hospital:

Primary Outcome Measures:
  • Quantification of integrated and unintegrated viral HIV-1 DNA in PBMCs [ Time Frame: Basal, week 12, week 24 and week 48 ]

Secondary Outcome Measures:
  • Quantification of residual HIV-1 (using an ultrasensitive RT-PCR assay with a lower limit of quantification of 5 copies/mL) [ Time Frame: Basal, week 1, week 2, week 4, week 8, week 12, week 24, week 36 and week 48 ]
  • Blips during the study (> 50 copies/mL, preceded and followed by determinations < 50 copies/mL in previous and posterior controls) [ Time Frame: Basal, week 4, week 8, week 12, week 24, week 36 and week 48 ]
  • Lymphocyte activation marker CD8+HLADR+CD38+ [ Time Frame: Basal, week 2, week 4, week 12, week 24 and week 48. ]
  • Raltegravir plasma trough concentration. [ Time Frame: Week 12, week 24 and week 48 ]
  • Level of apoptosis in CD4 and CD8 T cells. [ Time Frame: Week 48 and week 60 ]

Enrollment: 69
Study Start Date: November 2007
Study Completion Date: September 2009
Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A
MK-0518 400mg twice a day
Drug: MK-0518 400mg twice a day
Raltegravir, MK-0518
Other Name: Raltegravir
No Intervention: B
No intervention

Detailed Description:

While highly active antiretroviral therapy (HAART) reduces plasma HIV-1 levels to below the limits of detection with standard assays, replication-competent virus persist in a stable, latent reservoir in resting CD4+ T cells. So, there is a rapid resumption in plasma viremia when therapy is interrupted.

In addition to cellular reservoir, other pharmacologically privileged areas such as the central nervous system and the genital tract might act as additional sources of residual virus in patients with undetectable levels of plasma HIV-1 RNA. There is great current interest in strategies for depleting and eliminating this reservoir.

The antiviral potency of current regimens emerges as an important determinant of complete viral control. In certain patients, the latent reservoir decay can be hastened with treatment intensification.

An intensification with the HIV-1 integrase inhibitor Raltegravir (RAL) of a stable HAART regimen with persistent HIV-1 viral suppression could increase the slope of decay of the HIV-1 latent reservoir. This could provide further insight into this area, decrease the size of latent reservoir, and translate into clinical benefits for patients being simplified to maintenance monotherapy with RAL or in the HIV-1 rebound kinetics and slope after a programmed treatment interruption.

  Eligibility

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. HIV-1 infected adults (+18 years old).
  2. Complete virological suppression (<50 copies/mL) for += 12 months, including at least 3 times during the last year.
  3. Patients on HAART regimen including a PI or an NNRTI and at least two nucleotide inhibitors.
  4. 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 drug-related mutations or any polymorphism or mutation associated to MK-0518 resistance prior to first HAART (only if genotype is available).
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00554398


Locations
Spain
Hospital Germans Trias i Pujol
Badalona, Barcelona, Spain, 08916
Hospital de la Santa Creu i Sant Pau
Barcelona, Spain, 08025
Hospital Clínic I Provinical de Barcelona
Barcelona, Spain, 08036
Sponsors and Collaborators
Germans Trias i Pujol Hospital
Fundacio Lluita Contra la SIDA
Investigators
Principal Investigator: Martínez-Picado Javier, MD,PhD Irsi Caixa -Hospital Germans Trias i Pujol
Principal Investigator: Paredes Roger, MD,PhD Lluita contra la Sida Foundation
Principal Investigator: Clotet Bonaventura, MS,PhD Lluita contra la Sida Foundation
Study Director: Llibre Josep Mª, MD,PhD Lluita contra la SIDA Foundation
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: LLuita Sida Foundation
ClinicalTrials.gov Identifier: NCT00554398     History of Changes
Other Study ID Numbers: INTEGRAL
First Submitted: November 5, 2007
First Posted: November 6, 2007
Last Update Posted: November 13, 2009
Last Verified: November 2009

Keywords provided by Germans Trias i Pujol Hospital:
Raltegravir
MK-0518
Treatment intensification
HIV-1 latency
HIV eradication
treatment experienced

Additional relevant MeSH terms:
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Raltegravir Potassium
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
HIV Integrase Inhibitors
Integrase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action