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

This study has been completed.
Sponsor:
Collaborator:
Fundacio Lluita Contra la SIDA
Information provided by:
Germans Trias i Pujol Hospital
ClinicalTrials.gov Identifier:
NCT00554398
First received: November 5, 2007
Last updated: November 12, 2009
Last verified: November 2009

November 5, 2007
November 12, 2009
November 2007
May 2009   (final data collection date for primary outcome measure)
Quantification of integrated and unintegrated viral HIV-1 DNA in PBMCs [ Time Frame: Basal, week 12, week 24 and week 48 ] [ Designated as safety issue: No ]
Quantification of integrated and unintegrated viral HIV-1 DNA in PBMCs.
Complete list of historical versions of study NCT00554398 on ClinicalTrials.gov Archive Site
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Lymphocyte activation marker CD8+HLADR+CD38+ [ Time Frame: Basal, week 2, week 4, week 12, week 24 and week 48. ] [ Designated as safety issue: No ]
  • Raltegravir plasma trough concentration. [ Time Frame: Week 12, week 24 and week 48 ] [ Designated as safety issue: No ]
  • Level of apoptosis in CD4 and CD8 T cells. [ Time Frame: Week 48 and week 60 ] [ Designated as safety issue: No ]
  • Quantification of residual HIV-1 (using an ultrasensitive RT-PCR assay with a lower limit of quantification of 3 copies/mL)
  • Blips during the study (>50 copies/mL, preceeded and followed by determinations <50 copies/mL in previous and posterior controls
Not Provided
Not Provided
 
Impact of MK-0518 (Raltegravir) Intensification on HIV-1 Viral Latency in Patients With Previous Complete Viral Suppression
Impact of MK-0518 (Raltegravir) Intensification on HIV-1 Viral Latency in Patients With Previous Complete Viral Suppression

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.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
HIV Infections
Drug: MK-0518 400mg twice a day
Raltegravir, MK-0518
Other Name: Raltegravir
  • Experimental: A
    MK-0518 400mg twice a day
    Intervention: Drug: MK-0518 400mg twice a day
  • No Intervention: B
    No intervention
Llibre JM, Buzón MJ, Massanella M, Esteve A, Dahl V, Puertas MC, Domingo P, Gatell JM, Larrouse M, Gutierrez M, Palmer S, Stevenson M, Blanco J, Martinez-Picado J, Clotet B. Treatment intensification with raltegravir in subjects with sustained HIV-1 viraemia suppression: a randomized 48-week study. Antivir Ther. 2012;17(2):355-64. doi: 10.3851/IMP1917. Epub 2011 Sep 28.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
69
September 2009
May 2009   (final data collection date for primary outcome measure)

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).
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Spain
 
NCT00554398
INTEGRAL
No
LLuita Sida Foundation
Germans Trias i Pujol Hospital
Fundacio Lluita Contra la SIDA
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
Germans Trias i Pujol Hospital
November 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP