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

December 3, 2019 updated by: Germans Trias i Pujol Hospital
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

69

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
      • Barcelona, Spain, 08025
        • Hospital de La Santa Creu i Sant Pau
      • Barcelona, Spain, 08036
        • Hospital Clínic I Provinical de Barcelona
    • Barcelona
      • Badalona, Barcelona, Spain, 08916
        • Hospital Germans Trias i Pujol

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 99 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: A
MK-0518 400mg twice a day
Drug: MK-0518 400mg twice a day
Raltegravir, MK-0518
Other Names:
  • Raltegravir
No Intervention: B
No intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Quantification of integrated and unintegrated viral HIV-1 DNA in PBMCs
Time Frame: Basal, week 12, week 24 and week 48
Basal, week 12, week 24 and week 48

Secondary Outcome Measures

Outcome Measure
Time Frame
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
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
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.
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
Week 12, week 24 and week 48
Level of apoptosis in CD4 and CD8 T cells.
Time Frame: Week 48 and week 60
Week 48 and week 60

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Germans Trias i Pujol Hospital

Collaborators

Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2007

Primary Completion (Actual)

May 1, 2009

Study Completion (Actual)

September 1, 2009

Study Registration Dates

First Submitted

November 5, 2007

First Submitted That Met QC Criteria

November 5, 2007

First Posted (Estimate)

November 6, 2007

Study Record Updates

Last Update Posted (Actual)

December 4, 2019

Last Update Submitted That Met QC Criteria

December 3, 2019

Last Verified

December 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • INTEGRAL

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on HIV Infections

Clinical Trials on MK-0518 400mg twice a day

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Portugal

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe