A Study to Evaluate the Use of a Protease Inhibitor and of Interleukin-2 (IL-2) in the Treatment of Early HIV Infection

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00006154
First received: August 7, 2000
Last updated: September 4, 2013
Last verified: September 2013

August 7, 2000
September 4, 2013
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  • Virologic: A. Plasma viral load B. Tissue viral load (CNS, lymphoid tissues, genital tract) C. HIV DNA (proviral) levels in circulating mononuclear cells D. Phenotypic and genotypic antiretroviral drug resistance [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Immunologic: A. Evaluation of CD4, CD8, CD45RA, CD45RO phenotypes and defined activation markers B. Evaluation of the diversity and persistence of the T cell repertoire (CD4+, CD8+) in the circulation and lymphoid tissues [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Immunologic: C. Functional CD4+ cellular assays (class II MHC tetramers) D. Thymic regeneration as studied by the exclusion circle assay E. Evolution of Western blot banding patterns F. Evolution of anti-HIV neutralizing antibody levels [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Clinical: A. Minor opportunistic infections or AIDS-defining conditions B. Death C. Clinical or laboratory adverse events D. Evaluation of adherence to therapy E. Evaluation of lipodystrophy [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
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Complete list of historical versions of study NCT00006154 on ClinicalTrials.gov Archive Site
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A Study to Evaluate the Use of a Protease Inhibitor and of Interleukin-2 (IL-2) in the Treatment of Early HIV Infection
Randomized, Controlled, Open Label, Multi-Center Phase III Trial Comparing the Safety and Antiviral Activity of a Protease-Containing Regimen (d4T/ddI/IDV/RTV) Versus a Protease-Sparing Regimen (d4T/ddI/EFV) and the Ability of Interleukin-2 to Purge HIV From Latent Stores in Patients With Acute/Early HIV Infection

The purpose of this study is to look at the effectiveness of combination anti-HIV drug therapy (with protease inhibitors [PIs] or without) in patients with early HIV infections. This study also looks at whether a drug called interleukin-2 (IL-2) can boost the immune system of these patients.

Doctors are not sure which anti-HIV drug combination is best to use in patients who have early HIV infection and have never received anti-HIV treatment. PIs are anti-HIV drugs that decrease viral load (level of HIV in the blood). However, PIs can cause serious side effects in some patients. Doctors would like to know if a drug combination that does not contain a PI is just as good as one that contains PIs.

Studies have suggested that an antiretroviral drug regimen of the non-nucleoside agent efavirenz (EFV) in combination with two nucleoside analogues is effective at achieving maximal viral suppression. This provides an alternative treatment to that of the more toxic PI-containing regimen. This trial examines whether a nonPI regimen with EFV is more beneficial than a PI-containing regimen when each is used in combination with the same two nucleoside analogues. A second part of the study looks at whether the addition of IL-2 may offer immunologic benefits as a co-administered drug.

Patients are randomized to initiate antiretroviral therapy of a PI-based (stavudine/didanosine/ritonavir [RTV]/indinavir [IDV]) or nonPI-based (stavudine/didanosine/EFV) regimen. Within these treatment arms, they are stratified according to a positive or negative p24 antigen result. At Week 16, patients not achieving maximal viral suppression (lower than 50 copies/ml) have the option to add abacavir (ABC) or other drugs as intensification therapy. Those achieving virologic suppression (less than 50 copies/ml) are randomized either to receive IL-2 or not. At study entry, and after 12 months, tissue samples of CSF, lymph node, and genital secretions are obtained, with permission. Patients have physical exams, women of child-bearing potential have pregnancy tests, and blood samples are drawn at clinic visits 12-16 times a year over 3 years so that virologic and immunologic evaluations may be performed. Compensation for time and transportation is given.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
HIV Infections
  • Drug: Indinavir sulfate
    400 mg tablets equaling 1600 mg daily
    Other Name: IDV
  • Drug: Ritonavir
    100 mg liquid capsules equaling 400 mg daily
    Other Name: RTV
  • Drug: Abacavir sulfate
    300 mg capsules equaling 600 mg daily. Administration based on individual results after 16 weeks.
    Other Name: ABC
  • Drug: Efavirenz
    200 mg capsules equaling 600 mg daily
    Other Name: DMP
  • Drug: Stavudine
    30-40 mg capsules equaling 60 or 80 mg daily
    Other Name: d4T
  • Drug: Didanosine
    250-400 mg E.coated tablets equaling 250 or 400 mg daily
    Other Name: ddI
  • Drug: Aldesleukin
    Subcutaneous injection equaling 15 x 10^6 IU daily dose. Administration based on individual results after 16 weeks and randomization.
    Other Names:
    • Proleukin
    • IL-2
  • Experimental: A
    Patients will receive combination antiretroviral therapy with a protease inhibitor
    Interventions:
    • Drug: Indinavir sulfate
    • Drug: Ritonavir
    • Drug: Abacavir sulfate
    • Drug: Didanosine
    • Drug: Aldesleukin
  • Active Comparator: B
    Patients will receive combination antiretroviral therapy without a protease inhibitor
    Interventions:
    • Drug: Abacavir sulfate
    • Drug: Efavirenz
    • Drug: Stavudine
    • Drug: Didanosine
    • Drug: Aldesleukin
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*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
165
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Inclusion Criteria

Patients may be eligible for this study if they:

  • Have been infected recently with HIV. This will be determined by certain lab tests.
  • Are 18 years of age or older.
  • Are able to swallow a large number of pills.
  • Are willing to use barrier methods of birth control (such as condoms) during the study.

Exclusion Criteria

Patients will not be eligible for this study if they:

  • Abuse drugs or alcohol.
  • Have any condition that, in the opinion of the investigator, could impair their ability to participate in the study.
  • Are breast-feeding or pregnant.
  • Have received any prior anti-HIV drugs. (However, use of anti-HIV drugs to try to prevent infection more than 6 months prior to study entry is allowed.)
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Canada
 
NCT00006154
AI-07-001, CTN #124, 11530
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National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Allergy and Infectious Diseases (NIAID)
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Principal Investigator: Rafick-Pierre Sekaly
Principal Investigator: Brian Conway
National Institute of Allergy and Infectious Diseases (NIAID)
September 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP