HIV InfectionPhase 3NCT00025909
Intermittent vs. Continuous HAART to Treat Chronic HIV Infection
A Phase 3 study testing Leukapheresis in people with HIV Infection, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
This study will evaluate the effects of intermittent short cycles of HAART (highly active antiretroviral therapy) for treating HIV infection. HAART is a multi-drug regimen that is very effective in suppressing HIV and perhaps slowing or halting progression to AIDS. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- HIV Infection
- What is being tested?
- Leukapheresis
- Type of treatment
- Surgery or procedure
- How many people
- 90 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2001to Jan 2005
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Documentation of HIV-1 infection by licensed ELISA test kit and confirmed by a second method (e.g. Western Blot).
- Absolute CD4+ T-cell count of greater than or equal to 175/mm(3) within 30 days before randomization (For patients who are status post-splenectomy, also CD4+ T-cell greater than 20%).
- If the CD4+ T cell count is less than or equal to 200 cells/mm(3), the patient must be receiving PCP prophylaxis.
- Receiving at least 3-drug HAART with at least 1viral load test less than 500 copies/ml and within at least 6 months screening. Patients must be receiving an NNRTI or a PI at enrollment.
- A viral load of less than 50 copies/ml prior to enrollment.
- Age at least 18 years.
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- For women of childbearing potential, a negative pregnancy test (serum or urine) is required within 14 days prior to randomization.
- Laboratory values (within 30 days prior to randomization):
- AST no more than 5 X the upper limit of normal (ULN).
- Total or direct bilirubin no more than 2 X ULN unless there is a pattern consistent with Gilbert's syndrome or the patient is receiving indinavir.
- Creatinine no more than 2.0 mg/dL.
- Platelet count at least 50,000/microliter.
Who cannot join
- Concurrent malignancy, or any other disease state, requiring cytotoxic chemotherapy.
- Symptomatic for significant HIV-related illnesses, such as opportunistic infections and malignancies other than mucocutaneous Kaposi's sarcoma. A history of AIDS defining opportunistic infections other than mucocutaneous candida.
- Use experimental antiretrovirals less than or equal to 6 months prior to enrollment. An exception may be made for hydroxyurea according to the judgment of the Principal Investigator. Patients receiving IL-2 will be eligible, and will be required to cycle during an on-HAART period if they are randomized to the intermittent arm.
- Pregnant or breastfeeding.
- Significant cardiac, pulmonary, kidney, rheumatologic, gastrointestinal, or CNS disease as detectable on routine history, physical examination, or screening laboratory studies.
- Psychiatric illness that, in the opinion of the PI, might interfere with study compliance.
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- Active substance abuse or history of prior substance abuse that may interfere with protocol compliance or compromise patient safety.
- Refusal to practice safe sex or use precautions against pregnancy (effective birth control with barrier contraceptives or abstinence).
- Known history or laboratory evidence of chronic hepatitis B infection including surface antigen positivity.
- Receiving salvage HAART, i.e. no evidence of clinical resistance to licensed anti-retrovirals.
- Patients receiving nevirapine, abacavir amd single protease inhibitor regimes at the time of enrollment. Patients receiving these medications may switch to other approved agents, and if the plasma viremia remains less than 50 copies/ml at least 30 days later, they would be eligible for enrollment. Patients on the continuous arm may receive nevirapine or abacavir regimens while participating in that arm.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institute of Allergy and Infectious Diseases (NIAID)
Bethesda, Maryland, 20892
About this study
Official title: A Randomized, Controlled Trial of Short Cycle Intermittent Versus Continuous HAART for the Treatment of Chronic HIV Infection
This study will evaluate the effects of intermittent short cycles of HAART (highly active antiretroviral therapy) for treating HIV infection. HAART is a multi-drug regimen that is very effective in suppressing HIV and perhaps slowing or halting progression to AIDS. However, the treatment has significant drawbacks: it cannot completely rid the body of virus; long-term therapy carries a risk of toxicity (harmful side effects); and the regimen is difficult to comply with because many pills and capsules must be taken daily. When patients stop taking HAART, their HIV levels climb again. This study will see if giving HAART in short cycles of 7 days on, 7 days off, can keep viral levels low while maintaining CD4+ T cell counts.
HIV-infected people age 18 or older who are receiving HAART and have a viral load of less than 50 copies/ml and a CD4+ T cell count of at least 175 cells/mm3 may be eligible for this study. Candidates will be screened with a medical history and physical examination, blood and urine tests, and possibly a chest X-ray and electrocardiogram. Women of childbearing potential will have a pregnancy test.
Read more
Participants will be randomly assigned to either continue their current medication regimen or to take HAART in intermittent cycles of 7 days off, 7 days on. Patients will continue treatment for 72 weeks or until viral levels increase or CD4+ T cell counts decline to a level of concern.
Upon entering the study, patients will have blood tests to monitor the amount of virus in the blood, CD4+ T cell count, viral resistance to HAART medications, side effects of the drug, and immune response to HIV in the test tube. They will have clinic visits for a history, physical examination and blood draws every month for 12 months. At that time, depending on T cell counts and viral load, the number of visits may be reduced, but never less frequently than every other month.
Patients will also undergo leukapheresis-a procedure for collecting quantities of white blood cells-every 3 to 4 months while on the study. For this procedure, whole blood is collected through a needle in an arm vein (similar to donating blood). The blood is circulated through a cell separator where the white cells are removed, and the rest of the blood (plasma, red cells and platelets) is returned through the same needle or through a second one in the other arm. The collected white cells are used for special studies on the level and function of T cells and to detect hidden virus.
Read the detailed description
Although highly active antiretroviral therapy (HAART) has been successful in suppressing plasma HIV RNA levels in infected patients, it has not resulted in eradication of virus. It is now clear that virus replication persists despite undetectable plasma viremia in individuals receiving HAART. In this regard, withdrawing HAART, even after prolonged periods of virus suppression, leads to an almost universal rapid rebound of plasma viremia. It is also now clear that prolonged, continuous HAART carries a risk of significant toxicity and side effects. In addition, the monetary cost of HAART is prohibitive for many individuals and countries. These recent observations may argue for a different approach to HAART with the goals of : 1) durable suppression of virus replication, without an attempt at eradication, 2) minimization of toxicity and side effects and improvement in patient life-style, and 3) a reduction in cost. Therefore, we propose to study the virologic and immunologic effects of short cycle intermittent versus continuous HAART in HIV-infected individuals as a possible means to achieve these goals. In a pilot study of patients successfully treated with HAART, we have demonstrated that cycles of 7 days on HAART followed by 7 days off HAART can maintain suppression of plasma, lymph node, and resting CD4+ T cell HIV while maintaining CD4+ T cell counts for up to 1 year. It is the purpose of this study to further evaluate these observations with a randomized, controlled, intent-to-treat trial.
- Conditions
- HIV Infection
- Being tested
- Leukapheresis
- Keywords
- Therapy, Antiretrovirals, Interruption, CD4+ T Cell, Plasma Viremia, HIV, Treatment Experienced, Treatment Interuption
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LeukapheresisProcedure or surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Nov 2001 (estimated)
- Study startOct 2001
- Study completionJan 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionStudies 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
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Enrolment
- 90 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00025909
- Sponsor's protocol ID
- 020013
- Other IDs
- 02-I-0013
- Status last verified
- Jan 2005
- First submitted
- 31 Oct 2001
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
Garcia F, Plana M, Vidal C, Cruceta A, O'Brien WA, Pantaleo G, Pumarola T, Gallart T, Miro JM, Gatell JM. Dynamics of viral load rebound and immunological changes after stopping effective antiretroviral therapy. AIDS. 1999 Jul 30;13(11):F79-86. doi: 10.1097/00002030-199907300-00002.
PubMed 10449278Neumann AU, Tubiana R, Calvez V, Robert C, Li TS, Agut H, Autran B, Katlama C. HIV-1 rebound during interruption of highly active antiretroviral therapy has no deleterious effect on reinitiated treatment. Comet Study Group. AIDS. 1999 Apr 16;13(6):677-83. doi: 10.1097/00002030-199904160-00008.
PubMed 10397562Zhang L, Ramratnam B, Tenner-Racz K, He Y, Vesanen M, Lewin S, Talal A, Racz P, Perelson AS, Korber BT, Markowitz M, Ho DD. Quantifying residual HIV-1 replication in patients receiving combination antiretroviral therapy. N Engl J Med. 1999 May 27;340(21):1605-13. doi: 10.1056/NEJM199905273402101.
PubMed 10341272
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Controlled Trial of Short Cycle Intermittent Versus Continuous HAART for the Treatment of Chronic HIV Infection
- ClinicalTrials.gov ID
- NCT00025909
- Acronym / sponsor ID
- 020013
- Conditions
- HIV Infection
- Keywords
- Therapy, Antiretrovirals, Interruption, CD4+ T Cell, Plasma Viremia, HIV, Treatment Experienced, Treatment Interuption
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 90 participants
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- Oct 2001
- Study completion
- Jan 2005
- First posted
- 1 Nov 2001 (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.
This study will evaluate the effects of intermittent short cycles of HAART (highly active antiretroviral therapy) for treating HIV infection. HAART is a multi-drug regimen that is very effective in suppressing HIV and perhaps slowing or halting progression to AIDS. However, the treatment has significant drawbacks: it cannot completely rid the body of virus; long-term therapy carries a risk of toxicity (harmful side effects); and the regimen is difficult to comply with because many pills and capsules must be taken daily. When patients stop taking HAART, their HIV levels climb again. This study will see if giving HAART in short cycles of 7 days on, 7 days off, can keep viral levels low while maintaining CD4+ T cell counts.
HIV-infected people age 18 or older who are receiving HAART and have a viral load of less than 50 copies/ml and a CD4+ T cell count of at least 175 cells/mm3 may be eligible for this study. Candidates will be screened with a medical history and physical examination, blood and urine tests, and possibly a chest X-ray and electrocardiogram. Women of childbearing potential will have a pregnancy test.
Participants will be randomly assigned to either continue their current medication regimen or to take HAART in intermittent cycles of 7 days off, 7 days on. Patients will continue treatment for 72 weeks or until viral levels increase or CD4+ T cell counts decline to a level of concern.
Upon entering the study, patients will have blood tests to monitor the amount of virus in the blood, CD4+ T cell count, viral resistance to HAART medications, side effects of the drug, and immune response to HIV in the test tube. They will have clinic visits for a history, physical examination and blood draws every month for 12 months. At that time, depending on T cell counts and viral load, the number of visits may be reduced, but never less frequently than every other month.
Patients will also undergo leukapheresis-a procedure for collecting quantities of white blood cells-every 3 to 4 months while on the study. For this procedure, whole blood is collected through a needle in an arm vein (similar to donating blood). The blood is circulated through a cell separator where the white cells are removed, and the rest of the blood (plasma, red cells and platelets) is returned through the same needle or through a second one in the other arm. The collected white cells are used for special studies on the level and function of T cells and to detect hidden virus.
Detailed description
Although highly active antiretroviral therapy (HAART) has been successful in suppressing plasma HIV RNA levels in infected patients, it has not resulted in eradication of virus. It is now clear that virus replication persists despite undetectable plasma viremia in individuals receiving HAART. In this regard, withdrawing HAART, even after prolonged periods of virus suppression, leads to an almost universal rapid rebound of plasma viremia. It is also now clear that prolonged, continuous HAART carries a risk of significant toxicity and side effects. In addition, the monetary cost of HAART is prohibitive for many individuals and countries. These recent observations may argue for a different approach to HAART with the goals of : 1) durable suppression of virus replication, without an attempt at eradication, 2) minimization of toxicity and side effects and improvement in patient life-style, and 3) a reduction in cost. Therefore, we propose to study the virologic and immunologic effects of short cycle intermittent versus continuous HAART in HIV-infected individuals as a possible means to achieve these goals. In a pilot study of patients successfully treated with HAART, we have demonstrated that cycles of 7 days on HAART followed by 7 days off HAART can maintain suppression of plasma, lymph node, and resting CD4+ T cell HIV while maintaining CD4+ T cell counts for up to 1 year. It is the purpose of this study to further evaluate these observations with a randomized, controlled, intent-to-treat trial.
Study design
- Primary purpose
- Treatment
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (12 listed)
- Documentation of HIV-1 infection by licensed ELISA test kit and confirmed by a second method (e.g. Western Blot).
- Absolute CD4+ T-cell count of greater than or equal to 175/mm(3) within 30 days before randomization (For patients who are status post-splenectomy, also CD4+ T-cell greater than 20%).
- If the CD4+ T cell count is less than or equal to 200 cells/mm(3), the patient must be receiving PCP prophylaxis.
- Receiving at least 3-drug HAART with at least 1viral load test less than 500 copies/ml and within at least 6 months screening. Patients must be receiving an NNRTI or a PI at enrollment.
- A viral load of less than 50 copies/ml prior to enrollment.
Key exclusion criteria (11 listed)
- Concurrent malignancy, or any other disease state, requiring cytotoxic chemotherapy.
- Symptomatic for significant HIV-related illnesses, such as opportunistic infections and malignancies other than mucocutaneous Kaposi's sarcoma. A history of AIDS defining opportunistic infections other than mucocutaneous candida.
- Use experimental antiretrovirals less than or equal to 6 months prior to enrollment. An exception may be made for hydroxyurea according to the judgment of the Principal Investigator. Patients receiving IL-2 will be eligible, and will be required to cycle during an on-HAART period if they are randomized to the intermittent arm.
- Pregnant or breastfeeding.
- Significant cardiac, pulmonary, kidney, rheumatologic, gastrointestinal, or CNS disease as detectable on routine history, physical examination, or screening laboratory studies.
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 |
|---|---|---|
| Leukapheresis | Procedure or surgery | – |
Primary outcome
Not reported in the source record.
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 Mar 2008.
- Background: PubMed 10449278Garcia F, Plana M, Vidal C, Cruceta A, O'Brien WA, Pantaleo G, Pumarola T, Gallart T, Miro JM, Gatell JM. Dynamics of viral load rebound and immunological changes after stopping effective antiretroviral therapy. AIDS. 1999 Jul 30;13(11):F79-86. doi: 10.1097/00002030-199907300-00002.
- Background: PubMed 10397562Neumann AU, Tubiana R, Calvez V, Robert C, Li TS, Agut H, Autran B, Katlama C. HIV-1 rebound during interruption of highly active antiretroviral therapy has no deleterious effect on reinitiated treatment. Comet Study Group. AIDS. 1999 Apr 16;13(6):677-83. doi: 10.1097/00002030-199904160-00008.
- Background: PubMed 10341272Zhang L, Ramratnam B, Tenner-Racz K, He Y, Vesanen M, Lewin S, Talal A, Racz P, Perelson AS, Korber BT, Markowitz M, Ho DD. Quantifying residual HIV-1 replication in patients receiving combination antiretroviral therapy. N Engl J Med. 1999 May 27;340(21):1605-13. doi: 10.1056/NEJM199905273402101.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Leukapheresis in people with HIV Infection, 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 12 inclusion and 11 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 Mar 2008. 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.
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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00025909, which also lists 3 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 Mar 2008.