Clinical trial NCT00554398: Impact of MK-0518 (Raltegravir) Intensification on HIV-1 Viral Latency in Patients With Previous Complete Viral Suppression
Official title: Impact of MK-0518 (Raltegravir) Intensification on HIV-1 Viral Latency in Patients With Previous Complete Viral Suppression
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV Infections
Keywords: Raltegravir
MK-0518
Treatment intensification
HIV-1 latency
HIV eradication
treatment experienced
Lead sponsor: Germans Trias i Pujol Hospital
Sponsor class: OTHER
Collaborators: name: Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia
First posted: 2007-11-06
Enrollment: 69
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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 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).

Primary outcomes:
measure: Quantification of integrated and unintegrated viral HIV-1 DNA in PBMCs
timeFrame: Basal, week 12, week 24 and week 48
Secondary outcomes:
measure: Quantification of residual HIV-1 (using an ultrasensitive RT-PCR assay with a lower limit of quantification of 5 copies/mL)
timeFrame: Basal, week 1, week 2, week 4, week 8, week 12, week 24, week 36 and week 48
measure: Blips during the study (> 50 copies/mL, preceded and followed by determinations < 50 copies/mL in previous and posterior controls)
timeFrame: Basal, week 4, week 8, week 12, week 24, week 36 and week 48
measure: Lymphocyte activation marker CD8+HLADR+CD38+
timeFrame: Basal, week 2, week 4, week 12, week 24 and week 48.
measure: Raltegravir plasma trough concentration.
timeFrame: Week 12, week 24 and week 48
measure: Level of apoptosis in CD4 and CD8 T cells.
timeFrame: Week 48 and week 60
Other outcomes:
Locations:
city: Badalona
country: Spain
facility: Hospital Germans Trias i Pujol
state: Barcelona
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Clínic I Provinical de Barcelona
Study officials:
affiliation: Irsi Caixa -Hospital Germans Trias i Pujol
name: Martínez-Picado Javier, MD,PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Lluita contra la Sida Foundation
name: Paredes Roger, MD,PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Lluita contra la Sida Foundation
name: Clotet Bonaventura, MS,PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Lluita contra la SIDA Foundation
name: Llibre Josep Mª, MD,PhD
role: STUDY_DIRECTOR
References:
citation: Llibre JM, Buzon 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.