Effectiveness of Adding Interleukin-2 to Anti-HIV Drugs in Patients Recently Infected With HIV

This study has been completed.
Chiron Corporation
Agouron Pharmaceuticals
Glaxo Wellcome
Information provided by:
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
First received: November 3, 2000
Last updated: October 25, 2012
Last verified: October 2012

The purpose of this study is to see whether taking interleukin-2 (IL-2) and other anti-HIV drugs affects the course of HIV disease in patients with primary HIV infection (the time period that immediately follows infection with HIV).

After primary HIV infection, the actual infection is spread through an increasing amount of HIV virus in the body. Studies have shown that, by taking a combination of anti-HIV drugs, it is possible to reduce the amount of HIV in the body to almost undetectable levels. This study will find out if starting anti-HIV drugs during primary infection will interrupt or reduce the spread of HIV in patients' bodies.

Condition Intervention
HIV Infections
Drug: Lamivudine/Zidovudine
Drug: Nelfinavir mesylate
Drug: Aldesleukin

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Single Center, Randomized Open Label Study of Initial Interleukin-2 Compared to Delayed Interleukin-2 When Added to Zidovudine, 3TC and Nelfinavir In Order to Modulate Immune Function and to Sustain Suppression of HIV-1 Replication Among Those Persons With Primary or Early HIV Infection

Resource links provided by NLM:

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

Primary Outcome Measures:
  • To evaluate the dynamics of HIV in different tissue compartments of maximally suppressive antiretroviral (ART) medications with IL-2 influences, viral pathogenesis and immune responses to HIV infection. [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • To determine the patterns of immunologic activation as measured by cell surface marker levels, soluble and cell-associated cytokines when persons with acute or early HIV infection are treated with ART and IL-2. [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • To examine whether the extent of CD8+ cell antiviral activity as measured by non-cytotoxic and cytotoxic responses affects the kinetics of viral replication and viral load in blood plasma. [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • To determine whether a broad cellular immune response to HIV infection, measured by T cell repertoire, cytotoxic T cell lymphocyte function and CD4 T helper function correlates with the patterns of cellular immune antiviral responses [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To follow a cohort of HIV negative individuals that tested with the Options Project to use as a comparison group with the HIV positive individuals enrolling in this protocol. [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Enrollment: 398
Study Start Date: February 2003
Study Completion Date: October 2008
Primary Completion Date: August 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A
Patients beginning IL-2 treatment regimens after 4 weeks of study
Drug: Lamivudine/Zidovudine
300/150 mg respectively twice daily for 104 weeks. Patients who develop intolerence to AZT may use Stavudine (d4T) at a dose of 40 mg daily.
Other Name: Combivir
Drug: Nelfinavir mesylate
1250 mg twice daily for 104 weeks.
Other Name: NFV
Drug: Aldesleukin
7.5 million units twice daily. Treatment will last until conclusion of study.
Other Name: IL-2
Active Comparator: B
Patients beginning IL-2 treatment after some delay based on specified criteria
Drug: Lamivudine/Zidovudine
300/150 mg respectively twice daily for 104 weeks. Patients who develop intolerence to AZT may use Stavudine (d4T) at a dose of 40 mg daily.
Other Name: Combivir
Drug: Nelfinavir mesylate
1250 mg twice daily for 104 weeks.
Other Name: NFV
Drug: Aldesleukin
7.5 million units twice daily. Treatment will last until conclusion of study.
Other Name: IL-2

Detailed Description:

Following initial exposure to HIV, infection is established through the rapid replication of a homogeneous strain of the virus. Preliminary studies of combination antiretroviral therapy show that it is possible to reduce circulating HIV RNA to below detectable levels at this phase. Sustained suppression of viral replication or viral eradication may be possible only before HIV has become integrated in the immune system and undergone a number of quasi species mutations. This study will assess the feasibility of interrupting the natural course of HIV infection by using antiretroviral therapy soon after initial infection.

Nelfinavir (NFV) and zidovudine/lamivudine (Combivir) treatment starts as soon as possible and at most, 7 days from the diagnosis of HIV infection, and continues for 104 weeks. After 4 weeks of therapy patients are randomized to begin receiving IL-2 therapy or to delay starting it until Week 48. Patients may choose not to receive IL-2 treatment and remain in the study. Patients have clinic visits to measure viral load every 4 weeks. At a final clinic visit, physical examinations and collection of semen, cervical fluid, blood, and saliva specimens are done. Eligible consenting patients have a tonsil biopsy. Patients are reimbursed for participation in this study.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria

Patients may be eligible for this study if they:

  • Have recent HIV infection.
  • Are available for follow-up for at least 96 weeks.
  • Are at least 18 years old.
  • Use a barrier method of birth control.

Exclusion Criteria

Patients will not be eligible for this study if they:

  • Have a condition such as Epstein-Barr virus, CMV mononucleosis syndrome, or acute streptococcal pharyngitis.
  • Have taken anti-HIV therapy for over 4 weeks.
  • Have or have had cancer requiring chemotherapy or radiation therapy within 1 month of study entry and have not yet recovered from the effects.
  • Abuse alcohol and other drugs.
  • Are pregnant.
  • Have a condition which interferes with intestinal absorption, such as severe diarrhea.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00006441

United States, Alabama
University of Alabama- Birmingham
Birmingham, Alabama, United States, 35294
United States, California
Rick Hecht
San Francisco, California, United States, 941102859
Sponsors and Collaborators
Chiron Corporation
Agouron Pharmaceuticals
Glaxo Wellcome
Principal Investigator: Jay Levy
  More Information

Additional Information:
No publications provided

Responsible Party: Rona Siskind, DAIDS
ClinicalTrials.gov Identifier: NCT00006441     History of Changes
Other Study ID Numbers: AI-01-001, AIEDRP AI-01-001
Study First Received: November 3, 2000
Last Updated: October 25, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Virus Replication
Drug Therapy, Combination
HIV Protease Inhibitors
CD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
Biological Markers
Reverse Transcriptase Inhibitors
Anti-HIV Agents
Cytotoxicity, Immunologic
Acute Infection

Additional relevant MeSH terms:
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
Reverse Transcriptase Inhibitors
Lamivudine, zidovudine drug combination
HIV Protease Inhibitors
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 15, 2014