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

HIV Infections Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00554398
• Other study ID #: INTEGRAL
• Status: Completed
• Phase: Phase 3
• Start date: November 2007
• Est. completion date: September 2009

Study information

• Verified date: December 2019
• Source: Germans Trias i Pujol Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 69
• Est. completion date: September 2009
• Est. primary completion date: May 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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).

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• MK-0518 400mg twice a day
Raltegravir, MK-0518

Locations

Country	Name	City	State
Spain	Hospital Germans Trias i Pujol	Badalona	Barcelona
Spain	Hospital Clínic I Provinical de Barcelona	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona

Sponsors (2)

Lead Sponsor	Collaborator
Germans Trias i Pujol Hospital	Fundacio Lluita Contra la SIDA

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Quantification of integrated and unintegrated viral HIV-1 DNA in PBMCs		Basal, week 12, week 24 and week 48
Secondary	Quantification of residual HIV-1 (using an ultrasensitive RT-PCR assay with a lower limit of quantification of 5 copies/mL)		Basal, week 1, week 2, week 4, week 8, week 12, week 24, week 36 and week 48
Secondary	Blips during the study (> 50 copies/mL, preceded and followed by determinations < 50 copies/mL in previous and posterior controls)		Basal, week 4, week 8, week 12, week 24, week 36 and week 48
Secondary	Lymphocyte activation marker CD8+HLADR+CD38+		Basal, week 2, week 4, week 12, week 24 and week 48.
Secondary	Raltegravir plasma trough concentration.		Week 12, week 24 and week 48
Secondary	Level of apoptosis in CD4 and CD8 T cells.		Week 48 and week 60