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Intermittent Versus Continuous Medication in the Treatment of HIV

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00001967
First Posted: January 19, 2000
Last Update Posted: March 4, 2008
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by:
National Institutes of Health Clinical Center (CC)
  Purpose
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.

Condition Intervention Phase
HIV Infection Drug: HAART Phase 4

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: Immunologic and Virologic Studies of Intermittent Versus Continuous HAART in the Treatment of HIV Disease

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment: 123
Study Start Date: November 1999
Estimated Study Completion Date: November 2004
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.
  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

INCLUSION CRITERIA:

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.

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.

EXCLUSION CRITERIA:

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.

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.

  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00001967


Locations
United States, Maryland
National Institute of Allergy and Infectious Diseases (NIAID)
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00001967     History of Changes
Obsolete Identifiers: NCT00001134
Other Study ID Numbers: 000020
00-I-0020
First Submitted: January 18, 2000
First Posted: January 19, 2000
Last Update Posted: March 4, 2008
Last Verified: November 2004

Keywords provided by National Institutes of Health Clinical Center (CC):
HIV
HAART
Immunity
Toxicity
Resistance
Treatment Interruption

Additional relevant MeSH terms:
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases