HIV InfectionNCT00863668
Raltegravir Activity In Lymphoid Tissues
A study testing Efavirenz + Tenofovir DF/Emtricitabine, Raltegravir + Tenofovir DF/Emtricitabine and Colonoscopy with biopsies in people with HIV Infection and HIV Infections, run by University of Minnesota at 1 site in United States.
Trial summary
The reduction with antiretroviral therapy (ART) of HIV RNA in blood, and HIV RNA in infected cells and in viruses associated with the follicular dendritic cell (FDC) network in lymphatic tissues, typically follows a two-phase pattern of decline. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV Infection, HIV Infections
- What is being tested?
- Efavirenz + Tenofovir DF/Emtricitabine, Raltegravir + Tenofovir DF/Emtricitabine and Colonoscopy with biopsies
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2009to Mar 2011
- Phase
- Interventional
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- HIV positive (proven serologically at the time of screen, unless evidence for seroconversion)
- Evidence of recent (proven seroconversion within 4 months) or acute infection (HIV antibody negative, HIV RNA positive), or CD4 T Cells > 350 in peripheral blood and plasma viral load > 100,000 copies/ml
- Antiretroviral therapy naive (no prior history of antiretroviral therapy)
- Negative pregnancy test for eligible women of childbearing potential
Who cannot join
- Contraindication to surgical and endoscopic procedures (as judged by the principal investigator)
- Psychiatric or psychological illness that would make adherence to protocol procedures unlikely
- Pregnancy
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Minnesota Medical Center, Division of Infectious Diseases
Minneapolis, Minnesota, 55455
About this study
Official title: Decay Kinetics of HIV With the Integrase Inhibitor Raltegravir
The reduction with antiretroviral therapy (ART) of HIV RNA in blood, and HIV RNA in infected cells and in viruses associated with the follicular dendritic cell (FDC) network in lymphatic tissues, typically follows a two-phase pattern of decline. The half-life of the first-phase is about 1 day and that of the second phase is about 14 days, with comparable estimates for first-phase decay in SIV-infected rhesus macaques.
While substantial evidence supports the current view that first-phase decay reflects the death of activated CD4+ T cells infected before ART was begun, the sources of viral RNA in the second phase have not as yet been conclusively established. Possible sources of viral RNA that have been invoked in mathematical models, or for which there is experimental evidence, include longer-lived infected cells such as macrophages and resting CD4+ T cells, dissociation of virus from the FDC network, and productively infected CD4+ T cells that are not subject to clearance by host immune responses because of waning levels of HIV antigen.
Read more
Raltegravir (MK-0518) belongs to a new class of integrase inhibitors that potently suppress HIV and SIV replication, and reportedly markedly alters the second phase HIV decline in a way that challenges the current view that longer-lived infected cells are the source of virus in this phase. While mathematical modeling of decay of HIV RNA in blood was most consistent with 1) cells newly infected by long-lived cells, or 2) from activation of latently infected cells with full-length unintegrated HIV DNA as a source of second phase virus, we think the data are also quite consistent with the greater efficacy of integrase inhibitors in a particular cell type and/or anatomic site such as the gut.
In this protocol we will test the hypothesis that the rapid decrease in HIV replication associated with raltegravir is due to a more complete suppression of viral replication in lymphatic compartments such as lymph nodes and gastrointestinal lymphatic tissue. We will also investigate compartment-specific intracellular levels of raltegravir to potentially explain differences in changes in these compartments.
Read the detailed description
The study will evaluate rates of HIV elimination in peripheral blood in comparison to secondary lymphatic tissues, including inguinal lymph nodes (LN) and gastrointestinal lymphatic tissues (GALT). HIV-infected patients who are antiretroviral therapy (ART) naive and fit criteria to initiate ART will be randomized to either Truvada (tenofovir/emtricitabine) + Sustiva (efavirenz - 600mg qDAY orally - standard of care) or Truvada + Isentress (raltegravir - 400mg BID orally).
Patients will have a blood draw, a colonoscopy with biopsies, and inguinal lymph node excision at days 0, 2, 7, 14, and week 52. Plasma HIV RNA and CD4+ T cell quantitation will be performed conventionally. HIV mRNA will be quantitated in LN and GALT using in-situ hybridization (ISH). Immunohistochemistry (IHC) will be performed to quantitate changes in CD4+ cell numbers over time in tissues from each respective ART regimen.
- Conditions
- HIV Infection, HIV Infections
- Being tested
- Efavirenz + Tenofovir DF/Emtricitabine, Raltegravir + Tenofovir DF/Emtricitabine, Colonoscopy with biopsies, Inguinal Lymph Node Excision
- Keywords
- Infection, HIV 1, HIV, treatment naive
- Medical subject headings
- HIV Infections, Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Efavirenz + Tenofovir DF/EmtricitabineDrug
Also called Sustiva, EFV, Tenofovir, Tenofovir Disoproxil Fumarate
600mg QD for 52 weeks + 300mg/200mg QD for 52 weeks
Raltegravir + Tenofovir DF/EmtricitabineDrug
Also called Isentress, MK-0518, Tenofovir, Tenofovir Disoproxil Fumarate
400mg BID for 52 weeks + 300mg/200mg QD for 52 weeks
Colonoscopy with biopsiesProcedure or surgery
Also called Colonoscopy, Biopsy, Secondary, Lymphatic
Day 0, Day 2, Day 7, Day 14, Week 52
Inguinal Lymph Node ExcisionProcedure or surgery
Also called Secondary, Lymphatic, Tissue, Inguinal
Day 0, Day 2, Day 7, Day 14, Week 52
| Study group | Role | What they receive |
|---|---|---|
| Efavirenz | Active comparator | Not described Receives: Drug: Efavirenz + Tenofovir DF/Emtricitabine; Procedure: Colonoscopy with biopsies; Procedure: Inguinal Lymph Node Excision |
| Raltegravir | Experimental | Not described Receives: Drug: Raltegravir + Tenofovir DF/Emtricitabine; Procedure: Colonoscopy with biopsies; Procedure: Inguinal Lymph Node Excision |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of HIV mRNA Decline Measured in Peripheral Blood
Measured: 1 year
Rate of HIV mRNA Expression Decline Measured in Lymphatic Tissues
Measured: 1 year
CD4+ T Cell Number Increase in Peripheral Blood Over Time
Measured: 1 year
CD4+ T Cell Increase Quantified in Lymphatic Tissues Over Time
Measured: 1 year
Secondary outcomes (1)
Intracellular concentrations of antiretroviral drugs
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Mar 2009 (estimated)
- Study startMar 2009
- Primary completionMar 2010 (estimated)
- Study completionMar 2011 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIV InfectionStudies 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 N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Minnesota
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Timothy W Schacker, M.D., Principal investigator, University of Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00863668
- Sponsor's protocol ID
- 0901M57887
- Status last verified
- May 2015
- First submitted
- 16 Mar 2009
- Last updated
- 18 May 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 18 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Decay Kinetics of HIV With the Integrase Inhibitor Raltegravir
- ClinicalTrials.gov ID
- NCT00863668
- Acronym / sponsor ID
- 0901M57887
- Conditions
- HIV Infection, HIV Infections
- Keywords
- Infection, HIV 1, HIV, treatment naive
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of MinnesotaUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- Mar 2009
- Primary completion
- Mar 2010 (estimated)
- Study completion
- Mar 2011 (estimated)
- First posted
- 18 Mar 2009 (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.
The reduction with antiretroviral therapy (ART) of HIV RNA in blood, and HIV RNA in infected cells and in viruses associated with the follicular dendritic cell (FDC) network in lymphatic tissues, typically follows a two-phase pattern of decline. The half-life of the first-phase is about 1 day and that of the second phase is about 14 days, with comparable estimates for first-phase decay in SIV-infected rhesus macaques.
While substantial evidence supports the current view that first-phase decay reflects the death of activated CD4+ T cells infected before ART was begun, the sources of viral RNA in the second phase have not as yet been conclusively established. Possible sources of viral RNA that have been invoked in mathematical models, or for which there is experimental evidence, include longer-lived infected cells such as macrophages and resting CD4+ T cells, dissociation of virus from the FDC network, and productively infected CD4+ T cells that are not subject to clearance by host immune responses because of waning levels of HIV antigen.
Raltegravir (MK-0518) belongs to a new class of integrase inhibitors that potently suppress HIV and SIV replication, and reportedly markedly alters the second phase HIV decline in a way that challenges the current view that longer-lived infected cells are the source of virus in this phase. While mathematical modeling of decay of HIV RNA in blood was most consistent with 1) cells newly infected by long-lived cells, or 2) from activation of latently infected cells with full-length unintegrated HIV DNA as a source of second phase virus, we think the data are also quite consistent with the greater efficacy of integrase inhibitors in a particular cell type and/or anatomic site such as the gut.
In this protocol we will test the hypothesis that the rapid decrease in HIV replication associated with raltegravir is due to a more complete suppression of viral replication in lymphatic compartments such as lymph nodes and gastrointestinal lymphatic tissue. We will also investigate compartment-specific intracellular levels of raltegravir to potentially explain differences in changes in these compartments.
Detailed description
The study will evaluate rates of HIV elimination in peripheral blood in comparison to secondary lymphatic tissues, including inguinal lymph nodes (LN) and gastrointestinal lymphatic tissues (GALT). HIV-infected patients who are antiretroviral therapy (ART) naive and fit criteria to initiate ART will be randomized to either Truvada (tenofovir/emtricitabine) + Sustiva (efavirenz - 600mg qDAY orally - standard of care) or Truvada + Isentress (raltegravir - 400mg BID orally).
Patients will have a blood draw, a colonoscopy with biopsies, and inguinal lymph node excision at days 0, 2, 7, 14, and week 52. Plasma HIV RNA and CD4+ T cell quantitation will be performed conventionally. HIV mRNA will be quantitated in LN and GALT using in-situ hybridization (ISH). Immunohistochemistry (IHC) will be performed to quantitate changes in CD4+ cell numbers over time in tissues from each respective ART regimen.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Efavirenz | Active comparator | Drug: Efavirenz + Tenofovir DF/Emtricitabine, Procedure: Colonoscopy with biopsies, Procedure: Inguinal Lymph Node Excision |
| Raltegravir | Experimental | Drug: Raltegravir + Tenofovir DF/Emtricitabine, Procedure: Colonoscopy with biopsies, Procedure: Inguinal Lymph Node Excision |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- HIV positive (proven serologically at the time of screen, unless evidence for seroconversion)
- Evidence of recent (proven seroconversion within 4 months) or acute infection (HIV antibody negative, HIV RNA positive), or CD4 T Cells > 350 in peripheral blood and plasma viral load > 100,000 copies/ml
- Antiretroviral therapy naive (no prior history of antiretroviral therapy)
- Negative pregnancy test for eligible women of childbearing potential
Key exclusion criteria (3 listed)
- Contraindication to surgical and endoscopic procedures (as judged by the principal investigator)
- Psychiatric or psychological illness that would make adherence to protocol procedures unlikely
- Pregnancy
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 |
|---|---|---|
| Efavirenz + Tenofovir DF/EmtricitabineAlso: Sustiva, EFV, Tenofovir, Tenofovir Disoproxil Fumarate600mg QD for 52 weeks + 300mg/200mg QD for 52 weeks | Drug | Efavirenz |
| Raltegravir + Tenofovir DF/EmtricitabineAlso: Isentress, MK-0518, Tenofovir, Tenofovir Disoproxil Fumarate400mg BID for 52 weeks + 300mg/200mg QD for 52 weeks | Drug | Raltegravir |
| Colonoscopy with biopsiesAlso: Colonoscopy, Biopsy, Secondary, LymphaticDay 0, Day 2, Day 7, Day 14, Week 52 | Procedure or surgery | Efavirenz, Raltegravir |
| Inguinal Lymph Node ExcisionAlso: Secondary, Lymphatic, Tissue, InguinalDay 0, Day 2, Day 7, Day 14, Week 52 | Procedure or surgery | Efavirenz, Raltegravir |
Primary outcome
Rate of HIV mRNA Decline Measured in Peripheral Blood
Time frame: 1 year
Rate of HIV mRNA Expression Decline Measured in Lymphatic Tissues
Time frame: 1 year
CD4+ T Cell Number Increase in Peripheral Blood Over Time
Time frame: 1 year
CD4+ T Cell Increase Quantified in Lymphatic Tissues Over Time
Time frame: 1 year
1 secondary outcome
Intracellular concentrations of antiretroviral drugs
Time frame: 1 year
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 May 2015.
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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.
Timothy W Schacker, M.D. principal investigator
University of Minnesota
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Efavirenz + Tenofovir DF/Emtricitabine, Raltegravir + Tenofovir DF/Emtricitabine and Colonoscopy with biopsies in people with HIV Infection and HIV Infections, run by University of Minnesota at 1 site in United States.
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: withdrawn, as of the sponsor's last update on 18 May 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
Rate of HIV mRNA Decline Measured in Peripheral Blood (time frame: 1 year). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 18 May 2015.