The Effectiveness of Two Anti-HIV Treatments in HIV-Infected Patients

A Phase II Randomized, Double-Blind, Placebo-Controlled Trial of the Virologic Effect of Two Different Nucleoside Treatment Strategies (Zidovudine Versus Zidovudine in Combination With Didanosine) for HIV Infection in Subjects With CD4+ Counts >= 550 Cells/mm3

To determine the effects of zidovudine (AZT) alone and in combination with didanosine (ddI) on viral load in the lymphoid tissue and blood of antiretroviral-naive, HIV-infected patients with CD4 counts greater than or equal to 550 cells/mm3.

Recent studies have shown that during the asymptomatic phase (clinical latency) of HIV infection, there is an extraordinarily large number of infected CD4+ lymphocytes and macrophages throughout the lymphoid system, both in latent and productive states. These findings support the belief that early intervention therapy with reverse transcriptase inhibitors could prolong the clinical latency period.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Zidovudine; Drug: Didanosine

Detailed Description

Recent studies have shown that during the asymptomatic phase (clinical latency) of HIV infection, there is an extraordinarily large number of infected CD4+ lymphocytes and macrophages throughout the lymphoid system, both in latent and productive states. These findings support the belief that early intervention therapy with reverse transcriptase inhibitors could prolong the clinical latency period.

Patients are randomized to receive AZT alone, AZT plus ddI, or no therapy (placebo) daily for 48 weeks. Patients are followed at weeks 2, 4, and 8, and then every 8 weeks thereafter until week 48.

• Study Type: Interventional
• Enrollment: 105
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • 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
  • Nebraska
    • Omaha, Nebraska, United States, 681985130
      • Univ of Nebraska Med Ctr
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve Univ
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 191075098
      • Thomas Jefferson Univ Hosp
  • Texas
    • Galveston, Texas, United States, 775550435
      • Univ of Texas Galveston

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

Concurrent Medication:

Allowed:

• Antibiotics for bacterial infections as clinically indicated.
• Recombinant erythropoietin (EPO) and G-CSF as clinically indicated for grade 3 or worse anemia and neutropenia, respectively.
• Antipyretics.
• Analgesics.
• Allergy medications.
• Oral contraceptives.
• Nonprescription medications such as vitamins or herbal therapies.

Concurrent Treatment:

Allowed:

• Radiation therapy to local lesion only.
• Acupuncture.

Patients must have:

• HIV seropositivity.
• CD4 count >= 550 cells/mm3.
• No ARC or AIDS conditions by CDC criteria.
• Consent of parent or guardian if less than 18 years of age.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

• Presence of factors predisposing to pancreatitis such as active alcoholism.
• Other medical conditions that would interfere with study compliance.

Concurrent Medication:

Excluded:

• Other antiretrovirals or systemic immunomodulators.
• Systemic corticosteroids.
• Systemic cytotoxic chemotherapy.
• Intravenous pentamidine.

Concurrent Treatment:

Excluded:

• Radiation therapy except to local lesion.

Patients with the following prior conditions are excluded:

• History of chronic diarrhea, defined as more than four loose or watery stools on average daily for the past month.
• History of grade 2 or worse peripheral neuropathy.
• History of pancreatitis.
• Bacterial infection requiring antibiotics within 14 days prior to study entry.

Prior Medication:

Excluded:

• Prior HIV therapy with antiretrovirals or systemic immunomodulators.

Prior Treatment:

Excluded within 2 weeks prior to study entry:

• Transfusion.

Active substance abuse or alcoholism.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Study Chair: Carey J; Study Chair: Erice A; Study Chair: Balfour H; Study Chair: Henry K; Study Chair: Hasse A

Study record dates

Study Major Dates

• Study Completion (Actual): May 1, 1995

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 1, 2021
• Last Update Submitted That Met QC Criteria: October 28, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Drug Therapy, Combination; Didanosine; Zidovudine
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases; HIV Infections; Infections; Acquired Immunodeficiency Syndrome; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Antimetabolites; Zidovudine; Didanosine
• Other Study ID Numbers: ACTG 275; 11251 (Registry Identifier: DAIDS ES Registry Number)