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AzTrials

HIV InfectionPhase 4NCT00001967

Intermittent Versus Continuous Medication in the Treatment of HIV

A Phase 4 study testing HAART in people with HIV Infection, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Any age
Conditions the study is for
HIV Infection
What is being tested?
HAART
How many people
123 participants
Where
1 siteUnited States
Study dates
Nov 1999to Nov 2004
Phase
Phase 4
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 300/mm(3) within 30 days before randomization (For patients who are status post-splenectomy, also CD4+ T-cell greater than 20%). For patients in cohort 2, the lowest documented CD4+ T-cell count must be greater than or equal to 200 cells/mm(3).
  • Receiving HAART (at least 2 NRTIs and an NNRTI or a PI) with at least 1 viral load test below the limit of detection (at least less than 500 copies/ml) greater than or equal to 3 months for cohort 1 and 4 and greater than or equal to 6 months for cohorts 2, 3 and 5 before screening.
  • A confirmatory viral load of less than 50 copies/ml prior to enrollment.
  • Age at least 18 years.
  • For women of childbearing potential, a negative pregnancy test (serum or urine) is required within 14 days prior to randomization.
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  • Laboratory values (within 30 days prior to randomization):
  • AST no more than 5 times the upper limit of normal (ULN);
  • Total or direct bilirubin no more than 2 times the 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 microliters.
  • Willingness to provide blood samples for storage that may be used in future studies of HIV infection and/or immunopathogenesis.

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 .
  • Use of 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.
  • For cohort 1 and the extension of cohort 2, current use of IL-2 or history of use of IL-2 . Cohorts 2, 3, 4 and 5, patients must not be currently receiving cycles of IL-2.
  • For the extension of cohort 2, participation in previous STI studies or off HAART for greater than 2 weeks consecutively in the last year.
  • Pregnancy or breastfeeding during the study period.
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  • Significant cardiac, pulmonary, kidney, rheumatologic, gastrointestinal, or CNS disease as detectable on routine history, physical examination, or screening laboratory studies are excluded. If an abnormality is a contraindication to a specific drug, an alternative drug within the same class may be used.
  • Psychiatric illness that, in the opinion of the PI, might interfere with study compliance.
  • 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 or abstinence).
  • Known history or laboratory evidence of chronic hepatitis B infection including surface antigen positivity .
  • Patients not receiving salvage HAART, i.e. no evidence of clinical resistance to licensed antiretrovirals.
  • Patients in cohort 1 cannot be receiving nevirapine at the time of enrollment.
  • Patients receiving nevirapine or abacavir at time of enrollment.
  • Expanded access medications are not allowed at time of enrollment nor while on study.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • National Institute of Allergy and Infectious Diseases (NIAID)

    Bethesda, Maryland, 20892

Other trials in United States

About this study

Official title: Immunologic and Virologic Studies of Intermittent Versus Continuous HAART in the Treatment of HIV Disease

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. 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, and 2) minimization of toxicity and side effects and improvement in patient life-style. Therefore, we propose to study the virologic and immunologic effects of intermittent versus continuous HAART in HIV-infected individuals as a possible means to achieve these goals. The primary protocol, Cohort 1, will be a randomized controlled study of 35 individuals receiving continuous HAART and 35 individuals receiving intermittent HAART with intervals of one month off therapy followed by two months on therapy. A second cohort of 10 individuals will serve as a pilot of 2 arms of 5 patients each to evaluate the potential of shorter on-off cycles to maintain suppression of plasma virus and boost HIV-specific immune responses. An extension of Cohort 2 will add 5 patients to the 7 days on/7 days off HAART arm with modified exclusion criteria and procedure schedule. We will analyze CD4+ T-cell counts, viral load, incidence of toxicity and side effects, HIV-specific immune responses and viral resistance to therapy and characterize the virus during rebound plasma viremia.

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. 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, and; 2) minimization of toxicity and side effects and improvement in patient life-style. Therefore, we propose to study the virologic and immunologic effects of intermittent versus continuous HAART in HIV-infected individuals as a possible means to achieve these goals. The primary protocol, Cohort 1, will be a randomized controlled study of 45 individuals receiving continuous HAART and 45 individuals receiving intermittent HAART with intervals of one month off therapy followed by two months on therapy. A second cohort of 10 individuals will serve as a pilot study of 2 arms of 5 patients each to evaluate the potential of shorter on-off cycles to maintain suppression of plasma virus and boost HIV-specific immune responses. An extension of Cohort 2 will add 5 patients to the 7 days on/ 7 days off HAART arm with modified exclusion criteria and procedure schedule. Cohort 3 will be a pilot study of 5 individuals who will received 4 days off HAART followed by 3 days on HAART. Cohort 4 will be a pilot study of 8 individuals who will receive a once-daily HAART regimen administered as short cycle intermittent therapy of 7 days off drugs followed by 7 days on drugs. Cohort 5 will be a pilot study of 5 individuals who will receive 3 days off HAART followed by 4 days on HAART. We will analyze CD4+ T-cell counts, viral load, incidence of toxicity and side effects, HIV-specific immune responses and viral resistance to therapy and characterize the virus during rebound plasma viremia.

Conditions
HIV Infection
Being tested
HAART
Keywords
HIV, HAART, Immunity, Toxicity, Resistance, Treatment Interruption
Medical subject headings
HIV Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • HAARTDrug

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Jan 2000 (estimated)
  2. Study startNov 1999
  3. Study completionNov 2004

Resources

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 4
Primary purpose
Treatment
Enrolment
123 participants
IDs, dates and publications
ClinicalTrials.gov ID
NCT00001967
Sponsor's protocol ID
000020
Other IDs
00-I-0020
Status last verified
Nov 2004
First submitted
18 Jan 2000
Last updated
4 Mar 2008
Results posted
No

Publications

  • Neumann 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 10397562

  • Furtado MR, Callaway DS, Phair JP, Kunstman KJ, Stanton JL, Macken CA, Perelson AS, Wolinsky SM. Persistence of HIV-1 transcription in peripheral-blood mononuclear cells in patients receiving potent antiretroviral therapy. N Engl J Med. 1999 May 27;340(21):1614-22. doi: 10.1056/NEJM199905273402102.

    PubMed 10341273

  • Zhang 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

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing HAART 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 15 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

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 NCT00001967, 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.

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