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

Purpose

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.

Condition	Intervention	Phase
HIV Infections	Drug: Indinavir sulfate Drug: Ritonavir Drug: Abacavir sulfate Drug: Efavirenz Drug: Stavudine Drug: Didanosine Drug: Aldesleukin	Phase 3


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	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

Resource links provided by NLM:

MedlinePlus related topics: HIV/AIDS

U.S. FDA Resources

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:

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 ]
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 ]
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 ]
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 ]


Estimated Enrollment:	165

Arms	Assigned Interventions
Experimental: A Patients will receive combination antiretroviral therapy with a protease inhibitor	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: 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
Active Comparator: B Patients will receive combination antiretroviral therapy without a protease inhibitor	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

Arms

Assigned Interventions

Experimental: A

Patients will receive combination antiretroviral therapy with a protease inhibitor

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: 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

Active Comparator: B

Patients will receive combination antiretroviral therapy without a protease inhibitor

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

Detailed Description:

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.

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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.)

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00006154

Locations


Canada, British Columbia
Viridae Clinical Sciences / University of British Columbia
Vancouver, British Columbia, Canada
Canada, Quebec
Centre de traitment d'immunodeficience
Montreal, Quebec, Canada
Centre Hospitalier de la Universite de Montreal (CHUM)
Montreal, Quebec, Canada
Institut Thoracique de Montreal
Montreal, Quebec, Canada

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators


Principal Investigator:	Rafick-Pierre Sekaly
Principal Investigator:	Brian Conway

More Information


Responsible Party:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00006154 History of Changes
Other Study ID Numbers:	AI-07-001 CTN #124 11530 ( Registry Identifier: DAIDS-ES )
Study First Received:	August 7, 2000
Last Updated:	September 4, 2013

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):


Interleukin-2 Didanosine Drug Therapy, Combination Stavudine HIV Protease Inhibitors Ritonavir Indinavir	Virus Latency Reverse Transcriptase Inhibitors Anti-HIV Agents abacavir efavirenz Acute Infection

Additional relevant MeSH terms:


Infection Communicable Diseases HIV Infections Acquired Immunodeficiency Syndrome Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immunologic Deficiency Syndromes Immune System Diseases Slow Virus Diseases Ritonavir HIV Protease Inhibitors	Indinavir Aldesleukin Abacavir Stavudine Didanosine Efavirenz Protease Inhibitors Interleukin-2 Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-HIV Agents Anti-Retroviral Agents Antiviral Agents Anti-Infective Agents Cytochrome P-450 CYP3A Inhibitors

ClinicalTrials.gov processed this record on June 23, 2017