HIV InfectionsNCT00581802
HIV Resistance and Treatment Strategies
An observational study of HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
The purpose of this observational study is to characterize which immune system cells hide the latent reservoir of HIV by counting the number of latent HIV in different subsets of CD4 cells. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- HIV Infections
- How many people
- 89 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2007to Jan 2011
- Phase
- Observational
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Participants will be recruited from the Comprehensive Care Clinic, a clinic that provides care exclusively to HIV patients from middle Tennessee and surrounding states. Participants are screened and identified with the inclusion and exclusion criteria from the computerized medical records system. If the medical charts are tagged, the study nurse will speak to the selected participant at the participant's following appointment.
Who may be able to join
- HIV infected
- Antiretroviral therapy (ART) naive OR a history of treatment with highly active antiretroviral therapy (HAART), a currently detectable viral load greater than 500 copies/ml, about to begin second or later potentially suppressive antiretroviral regimen, and must meet the following two requirements:
- Viral load less than 50 copies/ml on the immediately prior regimen with less than 50 copies/ml measured on at least two visits during prior ART
- Viral load greater than 500 copies/ml on two consecutive visits and a history of failure during prior lamivudine- or emtricitabine-containing ART
- HIV infected
- Currently on HAART with an undetectable viral load of less than 50 copies/ml for 12 months prior to study entry (at least two measures). If the participant is on the second or later regimen of HAART, the previous regimen must have contained lamivudine or emtricitabine.
- HIV infected
- Currently taking or about to begin raltegravir with optimized background HAART
Who cannot join
- History of treatment with any two of the following: darunavir, tipranavir, or enfuvirtide
- Self-reported or clinician-reported nonadherence to earlier ART
- Current substance abuse that, in the opinion of the investigator, will increase the risk of nonadherence
- Weight less than 110 lbs
- Blood transfusion within the 6 months prior to study entry
- Platelets less than 50 cells/mm3
Show all 32Show fewer
- International normalized ratio (INR) greater than 2.0 if participants are on warfarin
- Heart disease with recent angina or myocardial infarction (MI) within 1 year prior to study entry
- Hematocrit 28% or less OR hemoglobin 8.0 g/dl or less
- Prior ART that included only one or two drugs
- Pregnancy
- Viral load "blip" greater than 2,000 copies/ml during current suppressive regimen
- Consistent low level viral load (between 50 and 2,000 copies/ml) during current regimen
- Change in currently suppressing HAART before study entry
- Self-reported or clinician-reported nonadherence to earlier antiretroviral regimens
- Current substance abuse that, in the opinion of the investigator, will increase the risk of nonadherence
- Weight less than 110 lbs
- Blood transfusion within the 6 months prior to study entry
- Platelets less than 50 cells/mm3
- INR greater than 2.0 if participants are on warfarin
- Heart disease with recent angina or MI within 1 year prior to study entry
- Hematocrit 28% or less OR hemoglobin 8.0 g/dl or less
- Prior ART that included only one or two drugs
- Pregnancy
- Current substance abuse that, in the opinion of the investigator, will increase the risk of nonadherence
- Weight less than 110 lbs
- Blood transfusion 6 months prior to study entry
- Platelets less than 50/mm3
- INR greater than 2.0 if participants are on warfarin
- Heart disease with recent angina or MI within 1 year prior to study entry
- • Hematocrit 28% or less OR hemoglobin 8.0 g/dl or less
- Pregnancy
Trial locations and contacts
1 site in 1 country.
United States1 site
Comprehensive Care Clinic/Center for AIDS Research
Nashville, Tennessee, 37203
About this study
Official title: Cohort Study to Understand Resistance and HIV Eradication (CURE): Observational Studies of Antiretroviral Drug Treatment Success and Failure
The purpose of this observational study is to characterize which immune system cells hide the latent reservoir of HIV by counting the number of latent HIV in different subsets of CD4 cells. Observations will also be made on other possible mechanisms of HIV persistence by looking at cellular factors such as APOBEC3 and drug transporters. The purpose of this study is to develop new strategies to reduce and possibly eliminate the latent reservoir in HIV infected adults.
Read the detailed description
Memory CD4 cells may provide a reservoir of latent HIV that cannot be completely eliminated using currently available anti-HIV medications. The overall goal of this observational study is to develop new strategies to eliminate the latent HIV reservoir in HIV infected individuals. CD4-cell subsets, cellular anti-HIV factors, and cellular drug transporters will be observed to determine which resting memory cells hide latent HIV and to determine the mechanisms responsible for the persistence of the latent HIV reservoir.
This study will last for at least 3 years. The screening visit will include medical history, contact information, urine collection, and a physical exam. Participants will be assigned to one of five groups:
- Group 1 will consist of intensively studied adults initiating potentially suppressive drug therapy. At the screening visit, Group 1 participants will be given the option to either undergo blood draws or leukapheresis for all visits.
- Group 2 will consist of intensively studied, well-suppressed adults on highly active antiretroviral therapy (HAART). At the screening visit, Group 2 participants will be given the option to either undergo blood draws or leukapheresis for all visits.
- Group 3 will consist of nonintensively studied adults initiating potentially suppressive drug therapy. Group 3 participants will undergo blood draws at all visits.
- Group 4 will consist of nonintensively studied, well-suppressed adults on HAART. Group 4 participants will undergo blood draws at all visits.
- Group 5 will consist of participants who are currently in the Merck Expanded Access Program receiving raltegravir. At the screening visit, Group 5 participants will be given the option to either undergo blood draws or leukapheresis for all visits.
For all participants undergoing blood draws only, visits will occur every 3 months for about 3 years. For patients undergoing leukapheresis, visits will occur every 6 months for about 3 years. At each visit, blood collection, documentation of current HAART, and updating of contact information will occur. Participants are encouraged to provide additional blood samples to be stored at all visits.
Participants in Groups 1, 2, or 5 may decline to be in the leukapheresis group at any time and will be given the option of continuing in the blood draw group or withdrawing completely from the study. If specimens are not obtained for any reason at any visit, participants in Groups 1, 2, or 5 will default to either Group 3 or Group 4. Antiretroviral medications will not be provided by this study.
- Conditions
- HIV Infections
- Keywords
- CD4-Positive T-Lymphocytes, Treatment Naive, Latent HIV Infections
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Intensively studied participants initiating potentially suppressive drug therapy. Group 1 participants may undergo optional leukapheresis. Group 1 participants may decline to be in the leukapheresis group at any time and will be given the option of continuing in the blood draw group or withdrawing from the study. If specimens are not obtained for any reason at any visit, Group 1 participants will default to either Group 3 or Group 4. | |
| 2 | Intensively studied, well-suppressed participants on HAART. Participants in Group 2 may undergo optional leukapheresis. Group 2 participants may decline to be in the leukapheresis group at any time and will be given the option of continuing in the blood draw group or withdrawing from the study. If specimens are not obtained for any reason at any visit, Group 2 participants will default to either Group 3 or Group 4. | |
| 3 | Nonintensively studied participants initiating potentially suppressive drug therapy | |
| 4 | Nonintensively studied well-suppressed participants on HAART | |
| 5 | Intensively studied participants who are currently participating in the Merck Expanded Access Program and receiving raltegravir. Participants in Group 5 may undergo optional leukapheresis. Group 5 participants may decline to be in the leukapheresis group at any time and will be given the option of continuing in the blood draw group or withdrawing from the study. If specimens are not obtained for any reason at any visit, Group 5 participants will default to either Group 3 or Group 4. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Establishment of a longitudinal, observational cohort of chemotherapeutically suppressed HIV participants to study cellular and virologic characteristics that enable HIV latency
Measured: At the end of the study
Secondary outcomes (7)
Characterization of memory CD4 cell subsets isolated from chemotherapeutically suppressed participants
Measured: At the end of the study
Quantification of the amount of latent HIV in each memory cell type in chemotherapeutically suppressed participants
Measured: At the end of the study
Evidence of HIV evolution
Measured: At the end of the study
Characterization of certain proteins in memory CD4-cell subsets in chemotherapeutically suppressed participants
Measured: At the end of the study
Determination of the association of protein regulation with cellular toxicity and the latent HIV reservoir in chemotherapeutically suppressed participants
Measured: At the end of the study
Characterization of the effects of immune activation on the latent reservoir of HIV
Measured: At the end of the study
Determination of the role of drug transporters in chemotherapeutically suppressed patients
Measured: At the end of the study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Dec 2007 (estimated)
- Study startJan 2007
- Study completionJan 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 89 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Vanderbilt University School of Medicine
- Responsible party
- Principal investigator, Richard T D'Aquila, National Institute of Allergy and Infectious Diseases (NIAID)
- Investigators
- Richard T. D'Aquila, MD, Principal investigator, Vanderbilt UniversityCarey K. Hwang, MD, PhD, Principal investigator, Vanderbilt University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00581802
- Sponsor's protocol ID
- 1R43AI062473-01
- Other IDs
- CURE
- Status last verified
- May 2012
- First submitted
- 19 Dec 2007
- Last updated
- 4 May 2012
- Results posted
- No
Publications
Noe A, Plum J, Verhofstede C. The latent HIV-1 reservoir in patients undergoing HAART: an archive of pre-HAART drug resistance. J Antimicrob Chemother. 2005 Apr;55(4):410-2. doi: 10.1093/jac/dki038. Epub 2005 Feb 22.
PubMed 15728140Pomerantz RJ. Reservoirs, sanctuaries, and residual disease: the hiding spots of HIV-1. HIV Clin Trials. 2003 Mar-Apr;4(2):137-43. doi: 10.1310/80jh-148k-nadq-u927.
PubMed 12671782Sedaghat AR, Siliciano JD, Brennan TP, Wilke CO, Siliciano RF. Limits on replenishment of the resting CD4+ T cell reservoir for HIV in patients on HAART. PLoS Pathog. 2007 Aug 31;3(8):e122. doi: 10.1371/journal.ppat.0030122.
PubMed 17784786Siliciano JD, Siliciano RF. A long-term latent reservoir for HIV-1: discovery and clinical implications. J Antimicrob Chemother. 2004 Jul;54(1):6-9. doi: 10.1093/jac/dkh292. Epub 2004 May 26.
PubMed 15163657
Study at a glance
From the registry record, last updated by the sponsor on 4 May 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cohort Study to Understand Resistance and HIV Eradication (CURE): Observational Studies of Antiretroviral Drug Treatment Success and Failure
- ClinicalTrials.gov ID
- NCT00581802
- Acronym / sponsor ID
- 1R43AI062473-01
- Conditions
- HIV Infections
- Keywords
- CD4-Positive T-Lymphocytes, Treatment Naive, Latent HIV Infections
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 89 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Collaborators
- Vanderbilt University School of Medicine
- Study start
- Jan 2007
- Study completion
- Jan 2011 (actual)
- First posted
- 28 Dec 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.
The purpose of this observational study is to characterize which immune system cells hide the latent reservoir of HIV by counting the number of latent HIV in different subsets of CD4 cells. Observations will also be made on other possible mechanisms of HIV persistence by looking at cellular factors such as APOBEC3 and drug transporters. The purpose of this study is to develop new strategies to reduce and possibly eliminate the latent reservoir in HIV infected adults.
Detailed description
Memory CD4 cells may provide a reservoir of latent HIV that cannot be completely eliminated using currently available anti-HIV medications. The overall goal of this observational study is to develop new strategies to eliminate the latent HIV reservoir in HIV infected individuals. CD4-cell subsets, cellular anti-HIV factors, and cellular drug transporters will be observed to determine which resting memory cells hide latent HIV and to determine the mechanisms responsible for the persistence of the latent HIV reservoir.
This study will last for at least 3 years. The screening visit will include medical history, contact information, urine collection, and a physical exam. Participants will be assigned to one of five groups:
- Group 1 will consist of intensively studied adults initiating potentially suppressive drug therapy. At the screening visit, Group 1 participants will be given the option to either undergo blood draws or leukapheresis for all visits.
- Group 2 will consist of intensively studied, well-suppressed adults on highly active antiretroviral therapy (HAART). At the screening visit, Group 2 participants will be given the option to either undergo blood draws or leukapheresis for all visits.
- Group 3 will consist of nonintensively studied adults initiating potentially suppressive drug therapy. Group 3 participants will undergo blood draws at all visits.
- Group 4 will consist of nonintensively studied, well-suppressed adults on HAART. Group 4 participants will undergo blood draws at all visits.
- Group 5 will consist of participants who are currently in the Merck Expanded Access Program receiving raltegravir. At the screening visit, Group 5 participants will be given the option to either undergo blood draws or leukapheresis for all visits.
For all participants undergoing blood draws only, visits will occur every 3 months for about 3 years. For patients undergoing leukapheresis, visits will occur every 6 months for about 3 years. At each visit, blood collection, documentation of current HAART, and updating of contact information will occur. Participants are encouraged to provide additional blood samples to be stored at all visits.
Participants in Groups 1, 2, or 5 may decline to be in the leukapheresis group at any time and will be given the option of continuing in the blood draw group or withdrawing completely from the study. If specimens are not obtained for any reason at any visit, participants in Groups 1, 2, or 5 will default to either Group 3 or Group 4. Antiretroviral medications will not be provided by this study.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| 1 | – | –Intensively studied participants initiating potentially suppressive drug therapy. Group 1 participants may undergo optional leukapheresis. Group 1 participants may decline to be in the leukapheresis group at any time and will be given the option of continuing in the blood draw group or withdrawing from the study. If specimens are not obtained for any reason at any visit, Group 1 participants will default to either Group 3 or Group 4. |
| 2 | – | –Intensively studied, well-suppressed participants on HAART. Participants in Group 2 may undergo optional leukapheresis. Group 2 participants may decline to be in the leukapheresis group at any time and will be given the option of continuing in the blood draw group or withdrawing from the study. If specimens are not obtained for any reason at any visit, Group 2 participants will default to either Group 3 or Group 4. |
| 3 | – | –Nonintensively studied participants initiating potentially suppressive drug therapy |
| 4 | – | –Nonintensively studied well-suppressed participants on HAART |
| 5 | – | –Intensively studied participants who are currently participating in the Merck Expanded Access Program and receiving raltegravir. Participants in Group 5 may undergo optional leukapheresis. Group 5 participants may decline to be in the leukapheresis group at any time and will be given the option of continuing in the blood draw group or withdrawing from the study. If specimens are not obtained for any reason at any visit, Group 5 participants will default to either Group 3 or Group 4. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Participants will be recruited from the Comprehensive Care Clinic, a clinic that provides care exclusively to HIV patients from middle Tennessee and surrounding states. Participants are screened and identified with the inclusion and exclusion criteria from the computerized medical records system. If the medical charts are tagged, the study nurse will speak to the selected participant at the participant's following appointment.
Key inclusion criteria (8 listed)
- HIV infected
- Antiretroviral therapy (ART) naive OR a history of treatment with highly active antiretroviral therapy (HAART), a currently detectable viral load greater than 500 copies/ml, about to begin second or later potentially suppressive antiretroviral regimen, and must meet the following two requirements:
- HIV infected
- Currently on HAART with an undetectable viral load of less than 50 copies/ml for 12 months prior to study entry (at least two measures). If the participant is on the second or later regimen of HAART, the previous regimen must have contained lamivudine or emtricitabine.
- HIV infected
Key exclusion criteria (32 listed)
- History of treatment with any two of the following: darunavir, tipranavir, or enfuvirtide
- Self-reported or clinician-reported nonadherence to earlier ART
- Current substance abuse that, in the opinion of the investigator, will increase the risk of nonadherence
- Weight less than 110 lbs
- Blood transfusion within the 6 months prior to study entry
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Establishment of a longitudinal, observational cohort of chemotherapeutically suppressed HIV participants to study cellular and virologic characteristics that enable HIV latency
Time frame: At the end of the study
7 secondary outcomes
Characterization of memory CD4 cell subsets isolated from chemotherapeutically suppressed participants
Time frame: At the end of the study
Quantification of the amount of latent HIV in each memory cell type in chemotherapeutically suppressed participants
Time frame: At the end of the study
Evidence of HIV evolution
Time frame: At the end of the study
Characterization of certain proteins in memory CD4-cell subsets in chemotherapeutically suppressed participants
Time frame: At the end of the study
Determination of the association of protein regulation with cellular toxicity and the latent HIV reservoir in chemotherapeutically suppressed participants
Time frame: At the end of the study
Characterization of the effects of immune activation on the latent reservoir of HIV
Time frame: At the end of the study
Determination of the role of drug transporters in chemotherapeutically suppressed patients
Time frame: At the end of the study
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 May 2012.
- Background: PubMed 15728140Noe A, Plum J, Verhofstede C. The latent HIV-1 reservoir in patients undergoing HAART: an archive of pre-HAART drug resistance. J Antimicrob Chemother. 2005 Apr;55(4):410-2. doi: 10.1093/jac/dki038. Epub 2005 Feb 22.
- Background: PubMed 12671782Pomerantz RJ. Reservoirs, sanctuaries, and residual disease: the hiding spots of HIV-1. HIV Clin Trials. 2003 Mar-Apr;4(2):137-43. doi: 10.1310/80jh-148k-nadq-u927.
- Background: PubMed 17784786Sedaghat AR, Siliciano JD, Brennan TP, Wilke CO, Siliciano RF. Limits on replenishment of the resting CD4+ T cell reservoir for HIV in patients on HAART. PLoS Pathog. 2007 Aug 31;3(8):e122. doi: 10.1371/journal.ppat.0030122.
- Background: PubMed 15163657Siliciano JD, Siliciano RF. A long-term latent reservoir for HIV-1: discovery and clinical implications. J Antimicrob Chemother. 2004 Jul;54(1):6-9. doi: 10.1093/jac/dkh292. Epub 2004 May 26.
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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.
Richard T. D'Aquila, MD principal investigator
Vanderbilt University
Carey K. Hwang, MD, PhD principal investigator
Vanderbilt University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) 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 8 inclusion and 32 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 May 2012. 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 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?
Establishment of a longitudinal, observational cohort of chemotherapeutically suppressed HIV participants to study cellular and virologic characteristics that enable HIV latency (time frame: At the end of the study). 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 NCT00581802, which also lists 4 linked publications.
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 May 2012; AzTrials last refreshed its copy on 7 Nov 2026.