HIV InfectionsPhase 3NCT00554398
Impact of MK-0518 (Raltegravir) Intensification on HIV-1 Viral Latency in Patients With Previous Complete Viral Suppression
A Phase 3 study testing MK-0518 400mg twice a day in people with HIV Infections, run by Germans Trias i Pujol Hospital at 3 sites in Spain.
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. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- HIV Infections
- What is being tested?
- MK-0518 400mg twice a day
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 69 participants
- Where
- 3 sitesSpain
- Study dates
- Nov 2007to Sep 2009
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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).
Trial locations and contacts
3 sites in 1 country.
Spain3 sites
Hospital Germans Trias i Pujol
Badalona, Barcelona, 08916
Hospital de la Santa Creu i Sant Pau
Barcelona, 08025
Hospital Clínic I Provinical de Barcelona
Barcelona, 08036
About this study
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.
Read the 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.
- Conditions
- HIV Infections
- Being tested
- MK-0518 400mg twice a day
- Keywords
- Raltegravir, MK-0518, Treatment intensification, HIV-1 latency, HIV eradication, treatment experienced
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MK-0518 400mg twice a dayDrug
Also called Raltegravir
Raltegravir, MK-0518
| Study group | Role | What they receive |
|---|---|---|
| A | Experimental | MK-0518 400mg twice a day Receives: Drug: MK-0518 400mg twice a day |
| B | No intervention | No intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
Quantification of integrated and unintegrated viral HIV-1 DNA in PBMCs
Measured: Basal, week 12, week 24 and week 48
Secondary outcomes (5)
Quantification of residual HIV-1 (using an ultrasensitive RT-PCR assay with a lower limit of quantification of 5 copies/mL)
Measured: 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)
Measured: Basal, week 4, week 8, week 12, week 24, week 36 and week 48
Lymphocyte activation marker CD8+HLADR+CD38+
Measured: Basal, week 2, week 4, week 12, week 24 and week 48.
Raltegravir plasma trough concentration.
Measured: Week 12, week 24 and week 48
Level of apoptosis in CD4 and CD8 T cells.
Measured: Week 48 and week 60
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2007 (estimated)
- Study startNov 2007
- Primary completionMay 2009
- Study completionSep 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 69 participants (actual)
Sponsor and investigators
- Lead sponsor
- Germans Trias i Pujol Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia
- Responsible party
- Sponsor
- Investigators
- Martínez-Picado Javier, MD,PhD, Principal investigator, Irsi Caixa -Hospital Germans Trias i PujolParedes Roger, MD,PhD, Principal investigator, Lluita contra la Sida FoundationClotet Bonaventura, MS,PhD, Principal investigator, Lluita contra la Sida FoundationLlibre Josep Mª, MD,PhD, Study director, Lluita contra la SIDA Foundation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00554398
- Sponsor's protocol ID
- INTEGRAL
- Status last verified
- Dec 2019
- First submitted
- 5 Nov 2007
- Last updated
- 4 Dec 2019
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 22290239
Study at a glance
From the registry record, last updated by the sponsor on 4 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of MK-0518 (Raltegravir) Intensification on HIV-1 Viral Latency in Patients With Previous Complete Viral Suppression
- ClinicalTrials.gov ID
- NCT00554398
- Acronym / sponsor ID
- INTEGRAL
- Conditions
- HIV Infections
- Keywords
- Raltegravir, MK-0518, Treatment intensification, HIV-1 latency, HIV eradication, treatment experienced
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 69 participants (actual)
- Lead sponsor
- Germans Trias i Pujol HospitalUniversity, hospital or other
- Collaborators
- Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia
- Study start
- Nov 2007
- Primary completion
- May 2009 (actual)
- Study completion
- Sep 2009 (actual)
- First posted
- 6 Nov 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A | Experimental | Drug: MK-0518 400mg twice a dayMK-0518 400mg twice a day |
| B | No intervention | –No intervention |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (3 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MK-0518 400mg twice a dayAlso: RaltegravirRaltegravir, MK-0518 | Drug | A |
Primary outcome
Quantification of integrated and unintegrated viral HIV-1 DNA in PBMCs
Time frame: Basal, week 12, week 24 and week 48
5 secondary outcomes
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
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
Lymphocyte activation marker CD8+HLADR+CD38+
Time frame: Basal, week 2, week 4, week 12, week 24 and week 48.
Raltegravir plasma trough concentration.
Time frame: Week 12, week 24 and week 48
Level of apoptosis in CD4 and CD8 T cells.
Time frame: Week 48 and week 60
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Dec 2019.
- Derived from this study: PubMed 22290239Llibre 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Martínez-Picado Javier, MD,PhD principal investigator
Irsi Caixa -Hospital Germans Trias i Pujol
Paredes Roger, MD,PhD principal investigator
Lluita contra la Sida Foundation
Clotet Bonaventura, MS,PhD principal investigator
Lluita contra la Sida Foundation
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing MK-0518 400mg twice a day in people with HIV Infections, run by Germans Trias i Pujol Hospital at 3 sites in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Quantification of integrated and unintegrated viral HIV-1 DNA in PBMCs (time frame: Basal, week 12, week 24 and week 48). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00554398, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Dec 2019.