Impact of MK-0518 (Raltegravir) Intensification on HIV-1 Viral Latency in Patients With Previous Complete Viral Suppression
Studieoversikt
Status
Forhold
Intervensjon / Behandling
Detaljert beskrivelse
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.
Studietype
Registrering (Faktiske)
Fase
- Fase 3
Kontakter og plasseringer
Studiesteder
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-
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Barcelona, Spania, 08025
- Hospital de La Santa Creu i Sant Pau
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Barcelona, Spania, 08036
- Hospital Clínic I Provinical de Barcelona
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Barcelona
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Badalona, Barcelona, Spania, 08916
- Hospital Germans Trías i Pujol
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-
Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
Beskrivelse
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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).
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
|
Eksperimentell: A
MK-0518 400mg twice a day
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Raltegravir, MK-0518
Andre navn:
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Ingen inngripen: B
No intervention
|
Hva måler studien?
Primære resultatmål
Resultatmål |
Tidsramme |
|---|---|
|
Quantification of integrated and unintegrated viral HIV-1 DNA in PBMCs
Tidsramme: Basal, week 12, week 24 and week 48
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Basal, week 12, week 24 and week 48
|
Sekundære resultatmål
Resultatmål |
Tidsramme |
|---|---|
|
Quantification of residual HIV-1 (using an ultrasensitive RT-PCR assay with a lower limit of quantification of 5 copies/mL)
Tidsramme: 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)
Tidsramme: 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+
Tidsramme: Basal, week 2, week 4, week 12, week 24 and week 48.
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Basal, week 2, week 4, week 12, week 24 and week 48.
|
|
Raltegravir plasma trough concentration.
Tidsramme: Week 12, week 24 and week 48
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Week 12, week 24 and week 48
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Level of apoptosis in CD4 and CD8 T cells.
Tidsramme: Week 48 and week 60
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Week 48 and week 60
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Samarbeidspartnere og etterforskere
Sponsor
Samarbeidspartnere
Etterforskere
- Hovedetterforsker: Martínez-Picado Javier, MD,PhD, Irsi Caixa -Hospital Germans Trias i Pujol
- Hovedetterforsker: Paredes Roger, MD,PhD, Lluita contra la Sida Foundation
- Hovedetterforsker: Clotet Bonaventura, MS,PhD, Lluita contra la Sida Foundation
- Studieleder: Llibre Josep Mª, MD,PhD, Lluita contra la Sida Foundation
Publikasjoner og nyttige lenker
Studierekorddatoer
Studer hoveddatoer
Studiestart
Primær fullføring (Faktiske)
Studiet fullført (Faktiske)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Anslag)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Nøkkelord
Ytterligere relevante MeSH-vilkår
- RNA-virusinfeksjoner
- Virussykdommer
- Infeksjoner
- Blodbårne infeksjoner
- Smittsomme sykdommer
- Seksuelt overførbare sykdommer, virale
- Seksuelt overførbare sykdommer
- Lentivirus infeksjoner
- Retroviridae-infeksjoner
- Immunologiske mangelsyndromer
- Sykdommer i immunsystemet
- HIV-infeksjoner
- Molekylære mekanismer for farmakologisk virkning
- Anti-infeksjonsmidler
- Antivirale midler
- Enzymhemmere
- Anti-HIV-midler
- Antiretrovirale midler
- HIV-integrasehemmere
- Integrasehemmere
- Raltegravir kalium
Andre studie-ID-numre
- INTEGRAL
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