The Effectiveness of Ritonavir Plus Zidovudine Plus Lamivudine in HIV-Infected Patients

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00001075
First received: November 2, 1999
Last updated: February 13, 2012
Last verified: February 2012
  Purpose

To determine whether administration of a highly active antiretroviral treatment regimen consisting of ritonavir (ABT-538), zidovudine (AZT), and lamivudine (3TC) is associated with the restoration of delayed type hypersensitivity and lymphocyte proliferative responses in patients with moderately advanced HIV-1 infection. To better characterize in these patients the phenotype of the expanded lymphocyte subpopulations, as well as the genotype, phenotype, and cellular origin of viruses that persist after initiation of therapy, and the genotype and phenotype of drug-resistant isolates that emerge during therapy.

Although plasma viral load drops dramatically after initiation of powerful antiretrovirals, it does not drop to zero. It appears that a new steady state is reached, suggesting that a reservoir may exist of virus-producing cells, possibly cells of monocyte/macrophage lineage, that continue to produce a low level of virus despite antiretroviral treatment.


Condition Intervention
HIV Infections
Drug: Ritonavir
Drug: Lamivudine
Drug: Zidovudine

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: A Pilot Study to Evaluate the Immunologic Consequences of a Highly Active Antiretroviral Therapy Regimen (HAART) Consisting of Ritonavir (ABT-538), Zidovudine (AZT), and Lamivudine (3TC) in Moderately Advanced HIV-1 Disease

Resource links provided by NLM:


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

Estimated Enrollment: 55
Study Completion Date: July 2007
Detailed Description:

Although plasma viral load drops dramatically after initiation of powerful antiretrovirals, it does not drop to zero. It appears that a new steady state is reached, suggesting that a reservoir may exist of virus-producing cells, possibly cells of monocyte/macrophage lineage, that continue to produce a low level of virus despite antiretroviral treatment.

Patients undergo 5 weeks of antiretroviral washout before initiating therapy with ritonavir alone for 9 days, followed by combination therapy with ritonavir, zidovudine, and lamivudine from day 10 through week 48. [AS PER AMENDMENT 1/31/97: The availability of the current, open-label study treatment has been extended to allow patients who have completed 48 weeks of therapy to continue protocol therapy until the last enrolled patient completes 48 weeks of study treatment.]

  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Concurrent Medication:

Allowed:

  • Recombinant erythropoietin and/or G-CSF for AZT-related bone marrow suppression.
  • Antibiotics other than metronidazole.
  • PCP prophylaxis.
  • Regularly prescribed medications such as antipyretics, analgesics, allergy medicine, and oral contraceptives.
  • Vitamins and herbal therapies.

Concurrent Treatment:

Allowed:

  • Acupuncture.
  • Visualization techniques.

Patients must have:

  • Documented HIV infection.
  • CD4 count 100-300 cells/mm3.
  • At least 3 consecutive months of prior AZT at a dosage of 500-600 mg bid, but with 5 weeks of antiretroviral washout prior to study entry.
  • Consent of parent or guardian if less than 18 years old.

Prior Medication:

Required:

  • Prior AZT at 500-600 mg bid at any time.
  • PCP prophylaxis during antiretroviral washout.

Allowed:

  • Prior ddI and/or ddC.
  • Prior recombinant erythropoietin and/or G-CSF for AZT-related bone marrow suppression.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

  • Chronic pancreatitis.
  • Psychological conditions that would affect compliance.
  • Intolerance to 500-600 mg/day AZT.
  • Concurrent participation on another antiretroviral research treatment study (study treatment for opportunistic infection or complications of HIV is allowed).
  • Considered likely to be noncompliant on study.

Concurrent Medication:

Excluded:

  • Immunomodulators such as systemic corticosteroids, thalidomide, or cytokines.
  • Rifabutin.
  • Disulfiram (Antabuse) or other medications with similar effects, including metronidazole.
  • Other drugs contraindicated with ritonavir.

[AS PER AMENDMENT 8/27/96: Immunization must be avoided during the antiretroviral washout period.]

Patients with the following prior conditions are excluded:

  • Active opportunistic infection or febrile illness with temperature >= 38.5 C within 3 days prior to study entry.
  • History of acute pancreatitis within the past 2 years.

Prior Medication:

Excluded:

  • Prior 3TC or a protease inhibitor.
  • Experimental drugs except those for HIV-related conditions, within the past 30 days.

[AS PER AMENDMENT 8/27/96: Immunization must be avoided prior to the antiretroviral washout period.]

Active substance abuse.

  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: NCT00001075

Locations
United States, Colorado
University of Colorado Hospital CRS
Aurora, Colorado, United States, 80045
United States, Illinois
Rush Univ. Med. Ctr. ACTG CRS
Chicago, Illinois, United States, 60612
United States, Ohio
Case CRS
Cleveland, Ohio, United States, 44106
Sponsors and Collaborators
Investigators
Study Chair: Lederman M
Study Chair: Kessler H
  More Information

Additional Information:
Publications:
Lederman M, Connick E, Landay A, Kessler H, Kuritzkes D, St Clair M, Fox L, Heath-Chiozzi M, Rousseau F, Spritzler J. Partial immune reconstitution after 12 weeks of HAART (AZT, 3TC, ritonavir) preliminary results of ACTG 315. Conf Retroviruses Opportunistic Infect. 1997 Jan 22-26;4th:208 (abstract no LB13)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00001075     History of Changes
Other Study ID Numbers: ACTG 315, 10688
Study First Received: November 2, 1999
Last Updated: February 13, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Drug Therapy, Combination
Acquired Immunodeficiency Syndrome
AIDS-Related Complex
Antiviral Agents
Zidovudine
HIV Protease Inhibitors
Ritonavir
Lamivudine

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
Zidovudine
Lamivudine
Ritonavir
HIV Protease Inhibitors
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents
Protease Inhibitors

ClinicalTrials.gov processed this record on July 20, 2014