Impact of MK-0518 (Raltegravir) Intensification on HIV-1 Viral Latency in Patients With Previous Complete Viral Suppression
- Conditions
- HIV Infections
- Interventions
- Drug: MK-0518 400mg twice a day
- Registration Number
- NCT00554398
- Lead Sponsor
- Germans Trias i Pujol Hospital
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 69
- HIV-1 infected adults (+18 years old).
- Complete virological suppression (<50 copies/mL) for += 12 months, including at least 3 times during the last year.
- Patients on HAART regimen including a PI or an NNRTI and at least two nucleotide inhibitors.
- Voluntary written informed consent.
- Pregnancy, or fertile women willing to be pregnant.
- Active substance abuse or major psychiatric disease.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description A MK-0518 400mg twice a day MK-0518 400mg twice a day
- Primary Outcome Measures
Name Time Method Quantification of integrated and unintegrated viral HIV-1 DNA in PBMCs Basal, week 12, week 24 and week 48
- Secondary Outcome Measures
Name Time Method Lymphocyte activation marker CD8+HLADR+CD38+ Basal, week 2, week 4, week 12, week 24 and week 48. 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 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 Level of apoptosis in CD4 and CD8 T cells. Week 48 and week 60 Raltegravir plasma trough concentration. Week 12, week 24 and week 48
Trial Locations
- Locations (3)
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Hospital Germans Trias i Pujol
🇪🇸Badalona, Barcelona, Spain
Hospital ClÃnic I Provinical de Barcelona
🇪🇸Barcelona, Spain