A Study of Three Treatment Combinations Using Zidovudine Plus Lamivudine Plus Indinavir in HIV-Infected Patients

October 28, 2021 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

A Prospective Randomized Double-Blind Trial of Three Maintenance Regimens for HIV-Infected Subjects Receiving Induction Therapy With Zidovudine, Lamivudine and Indinavir

To compare the proportion of patients who sustain suppression of plasma HIV RNA to undetectable levels [AS PER AMENDMENT 09/19/97: below 200 copies/mL by Roche UltraSensitive assay] among the 3 regimens during the maintenance phase.

The objective of antiretroviral therapy is to reduce HIV replication, preserve immunologic function and delay the development of HIV-related complications. In patients administered potent antiretroviral regimens, HIV RNA levels are reduced below 500 copies/ml of plasma and below the level of detection of commercially available assays. This protocol attempts to learn if a less intensive regimen can successfully sustain viral suppression after induction with a triple-drug regimen. The study also addresses whether HIV can be eradicated in patients following prolonged treatment with induction and maintenance regimens.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The objective of antiretroviral therapy is to reduce HIV replication, preserve immunologic function and delay the development of HIV-related complications. In patients administered potent antiretroviral regimens, HIV RNA levels are reduced below 500 copies/ml of plasma and below the level of detection of commercially available assays. This protocol attempts to learn if a less intensive regimen can successfully sustain viral suppression after induction with a triple-drug regimen. The study also addresses whether HIV can be eradicated in patients following prolonged treatment with induction and maintenance regimens.

All patients will receive open label induction therapy with zidovudine (ZDV), lamivudine (3TC) and indinavir (IDV) for 6 months. Following the 6 month induction phase, patients with undetectable plasma HIV RNA at weeks 16, 20 and 24 will enter the maintenance phase [blinded maintenance phase AS PER AMENDMENT 09/19/97] and be randomized to one of three maintenance regimens, i.e., either continued ZDV/3TC/IDV (control), or ZDV/3TC/IDV placebo or ZDV placebo/3TC placebo/IDV. Prior to randomization, patients are stratified according to entry HIV RNA level (greater than or equal to 30,000 or less than 30,000 copies/ml) and by prior ZDV therapy (at least 7 days or less than 7 days). After 12 months [AS PER AMENDMENT 09/19/97: 18 months] of maintenance therapy, treatment will be withdrawn at 6-month intervals in randomly-selected patients who have achieved undetectable HIV RNA. AS PER 09/19/97 AMENDMENT: After 18 months of blinded maintenance therapy, treatment is unblinded for patients whose HIV RNA levels remain detectable. Such patients receive optimal therapy, either continuing the protocol regimen or initiating alternative therapy.

AS PER AMENDMENT 2/27/98: An interim review conducted in January, 1998 demonstrated that the strategy of less intensive antiviral therapy after 6 months of IDV/3TC/ZDV induction therapy is less effective than continuation of triple drug therapy except for ZDV-naive patients assigned to ZDV/3TC. Therefore, the maintenance phase of this study has been discontinued.

Patients currently on blinded maintenance are unblinded immediately and have the option of reinitiating open-label triple therapy with IDV/3TC/ZDV or discontinuing study treatment. Patients currently on induction may register for continued open-label triple therapy or may discontinue study treatment. This amendment allows treatment extension so that subjects may receive open-label triple therapy until May 31, 1998. At that time, a rollover protocol or another modification with a longer period of drug supply may become available. Patients who choose to go off treatment are followed until May 31, 1998.

AS PER AMENDMENT 04/23/98: This study will now provide treatment with open-label ZDV/3TC/IDV until August 1, 1998. A rollover protocol or another 343 protocol modification with a longer period of drug supply may become available, but this cannot be guaranteed.

AS PER AMENDMENT 06/19/98: This study will now provide treatment with open-label ZDV/3TC/IDV until either November 1, 1998 or until 3 months after the rollover study (A5025) is available to the study sites (whichever comes first).

Study Type

Interventional

Enrollment

500

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 900331079
        • Univ of Southern California / LA County USC Med Ctr
      • San Diego, California, United States, 921036325
        • Univ of California / San Diego Treatment Ctr
      • San Francisco, California, United States, 94115
        • Stanford at Kaiser / Kaiser Permanente Med Ctr
      • San Francisco, California, United States, 941102859
        • San Francisco Gen Hosp
      • San Jose, California, United States, 951282699
        • Santa Clara Valley Med Ctr / AIDS Community Rsch Consortium
      • Stanford, California, United States, 943055107
        • San Mateo AIDS Program / Stanford Univ
      • Stanford, California, United States, 943055107
        • Stanford Univ Med Ctr
      • Torrance, California, United States, 90502
        • Harbor UCLA Med Ctr
    • Colorado
      • Denver, Colorado, United States, 80262
        • Univ of Colorado Health Sciences Ctr
    • Florida
      • Miami, Florida, United States, 331361013
        • Univ of Miami School of Medicine
    • Georgia
      • Atlanta, Georgia, United States, 30308
        • Emory Univ
    • Hawaii
      • Honolulu, Hawaii, United States, 96816
        • Univ of Hawaii
      • Honolulu, Hawaii, United States, 96816
        • Queens Med Ctr
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern Univ Med School
      • Chicago, Illinois, United States, 60612
        • Cook County Hosp
    • Indiana
      • Indianapolis, Indiana, United States, 462025250
        • Indiana Univ Hosp
      • Indianapolis, Indiana, United States, 46202
        • Division of Inf Diseases/ Indiana Univ Hosp
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • Univ of Iowa Hosp and Clinic
    • Louisiana
      • New Orleans, Louisiana, United States, 70112
        • Tulane Univ School of Medicine
      • New Orleans, Louisiana, United States, 70112
        • Tulane Med Ctr Hosp
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Johns Hopkins Hosp
      • Baltimore, Maryland, United States, 212052196
        • State of MD Div of Corrections / Johns Hopkins Univ Hosp
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Harvard (Massachusetts Gen Hosp)
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess - West Campus
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • Univ of Minnesota
      • Minneapolis, Minnesota, United States, 55415
        • Hennepin County Med Clinic
      • Saint Paul, Minnesota, United States, 55101
        • St Paul Ramsey Med Ctr
    • Missouri
      • Saint Louis, Missouri, United States, 63112
        • St Louis Regional Hosp / St Louis Regional Med Ctr
    • Nebraska
      • Omaha, Nebraska, United States, 681985130
        • Univ of Nebraska Med Ctr
    • New York
      • New York, New York, United States, 10003
        • Beth Israel Med Ctr
      • New York, New York, United States, 10016
        • Bellevue Hosp / New York Univ Med Ctr
      • New York, New York, United States, 10021
        • Mem Sloan - Kettering Cancer Ctr
      • New York, New York, United States, 10029
        • Mount Sinai Med Ctr
      • New York, New York, United States, 10019
        • Saint Clare's Hosp and Health Ctr
      • Rochester, New York, United States, 14642
        • Univ of Rochester Medical Center
    • North Carolina
      • Chapel Hill, North Carolina, United States, 275997215
        • Univ of North Carolina
      • Charlotte, North Carolina, United States, 28203
        • Carolinas Med Ctr
      • Greensboro, North Carolina, United States, 27401
        • Moses H Cone Memorial Hosp
    • Ohio
      • Cincinnati, Ohio, United States, 452670405
        • Univ of Cincinnati
      • Cleveland, Ohio, United States, 44106
        • Case Western Reserve Univ
      • Cleveland, Ohio, United States, 441091998
        • MetroHealth Med Ctr
      • Columbus, Ohio, United States, 432101228
        • Ohio State Univ Hosp Clinic
    • South Carolina
      • West Columbia, South Carolina, United States, 29169
        • Julio Arroyo
    • Texas
      • Galveston, Texas, United States, 775550435
        • Univ of Texas Galveston
    • Washington
      • Seattle, Washington, United States, 981224304
        • Univ of Washington

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria

Patients must have:

  • Documented HIV infection.
  • A CD4 cell count >= 200 cells/mm3 within 90 days prior to study entry.
  • Plasma HIV RNA >= 1000 copies/ml within 90 days prior to study entry.

Exclusion Criteria

Co-existing Condition:

Patients with any of the following conditions or symptoms are excluded:

  • A malignancy that requires systemic chemotherapy.

Concurrent Medication:

Excluded:

  • Oral ketoconazole (Nizoral), terfenadine (Seldane), astemizole (Hismanal), cisapride (Propulsid), triazolam (Halcion) or midazolam (Versed).
  • All antiretroviral therapies other than study medications.
  • Rifabutin and rifampin.
  • Investigational drugs and vaccines.
  • Systemic cytotoxic chemotherapy.
  • Interferon, interleukins, GM-CSF and HIV vaccines.

Patients with any of the following prior conditions are excluded:

  • Unexplained temperature > 38.5 degrees C for any 7 days within 30 days prior to study entry.
  • Chronic diarrhea as defined as > 3 liquid stools per day persisting for 15 days within 30 days prior to study entry.
  • Proven or suspected acute hepatitis within 30 days prior to study entry, even if AST and ALT are <= 5.0 X ULN (upper limit of normal).
  • A history of >= Grade 2 bilateral peripheral neuropathy within 60 days prior to study entry.
  • A history of intolerance to 300 mg/day of ZDV defined as any toxicity requiring a dose reduction or termination of ZDV.

Prior Medication:

Excluded:

  • Acute therapy for an infection or other medical illness within 14 days prior to study entry.
  • Any prior therapy with 3TC or experimental drug 1592.
  • More than 2 weeks of lifetime exposure to protease inhibitor therapy; any exposure within 14 days prior to study entry.
  • Interferons, interleukins, GM-CSF or HIV vaccines within 30 days prior to study entry.
  • Any experimental therapy (drugs or vaccines) within 30 days prior to study entry.
  • Rifampin or rifabutin within 14 days prior to study entry.
  • Systemic cytotoxic chemotherapy within 30 days prior to study entry.
  • Oral ketoconazole (Nizoral), terfenadine (Seldane), astemizole (Hismanal), cisapride (Propulsid), triazolam (Halcion) or midazolam (Versed).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Masking: Double

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

  • Study Chair: Havlir D
  • Study Chair: Richman D

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Completion (Actual)

December 1, 1997

Study Registration Dates

First Submitted

November 2, 1999

First Submitted That Met QC Criteria

August 30, 2001

First Posted (Estimate)

August 31, 2001

Study Record Updates

Last Update Posted (Actual)

November 4, 2021

Last Update Submitted That Met QC Criteria

October 28, 2021

Last Verified

October 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ACTG 343
  • 11314 (Registry Identifier: DAIDS ES Registry Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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