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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: Indinavir sulfate
* Drug: Ritonavir
* Drug: Abacavir sulfate
* Drug: Efavirenz
* Drug: Stavudine
* Drug: Didanosine
* Drug: Aldesleukin


Participation Criteria
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Eligibility Criteria
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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.)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>Patients will receive combination antiretroviral therapy with a protease inhibitor | Drug: Indinavir sulfate<br>* 400 mg tablets equaling 1600 mg daily<br>* Other names: IDV;Drug: Ritonavir<br>* 100 mg liquid capsules equaling 400 mg daily<br>* Other names: RTV;Drug: Abacavir sulfate<br>* 300 mg capsules equaling 600 mg daily. Administration based on individual results after 16 weeks.<br>* Other names: ABC;Drug: Didanosine<br>* 250-400 mg E.coated tablets equaling 250 or 400 mg daily<br>* Other names: ddI;Drug: Aldesleukin<br>* Subcutaneous injection equaling 15 x 10^6 IU daily dose. Administration based on individual results after 16 weeks and randomization.<br>* Other names: IL-2;|
| Active Comparator: B<br>Patients will receive combination antiretroviral therapy without a protease inhibitor | Drug: Abacavir sulfate<br>* 300 mg capsules equaling 600 mg daily. Administration based on individual results after 16 weeks.<br>* Other names: ABC;Drug: Efavirenz<br>* 200 mg capsules equaling 600 mg daily<br>* Other names: DMP;Drug: Stavudine<br>* 30-40 mg capsules equaling 60 or 80 mg daily<br>* Other names: d4T;Drug: Didanosine<br>* 250-400 mg E.coated tablets equaling 250 or 400 mg daily<br>* Other names: ddI;Drug: Aldesleukin<br>* Subcutaneous injection equaling 15 x 10^6 IU daily dose. Administration based on individual results after 16 weeks and randomization.<br>* Other names: IL-2;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |  | 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 |  | 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 |  | 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 |  | Throughout study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Interleukin-2, Didanosine, Drug Therapy, Combination, Stavudine, HIV Protease Inhibitors, Ritonavir, Indinavir, Virus Latency, Reverse Transcriptase Inhibitors, Anti-HIV Agents, abacavir, efavirenz, Acute Infection