Phase I Pharmacokinetic and Tolerance Study of Ribavirin in Human Immunodeficiency Virus (HIV) - Infected Patients

To determine how fast ribavirin reaches the bloodstream, what concentration of ribavirin is reached in blood and how long it remains in the blood (pharmacokinetics) when given by different routes of administration. To find the maximum tolerated dose (MTD) of ribavirin. The effects of ribavirin on the immune system, and on the virus will be measured by T4 cell count and p24 antigen levels.

Early studies with ribavirin in patients with AIDS and AIDS related complex (ARC) have shown that ribavirin appears to inhibit the spread of the virus. Determination of how much and how often to give the drug will require further knowledge of the pharmacokinetics and toxicity of the drug in patients with AIDS or ARC and in chronic virus carriers who do not have symptoms.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Ribavirin

Detailed Description

Early studies with ribavirin in patients with AIDS and AIDS related complex (ARC) have shown that ribavirin appears to inhibit the spread of the virus. Determination of how much and how often to give the drug will require further knowledge of the pharmacokinetics and toxicity of the drug in patients with AIDS or ARC and in chronic virus carriers who do not have symptoms.

Ribavirin is given to HIV-infected patients intravenously as a timed 30-min infusion at 1 of 5 single doses; 2 weeks later, the same doses are given orally in a single dose. Following at least 2 additional weeks, 6 patients are then given ribavirin at the lowest dose twice a day for 16 weeks. They are evaluated for tolerance and the next group is given a higher dose. Each successive group begins at 3-week intervals to receive doses that increase each day until the MTD is reached. Blood samples taken periodically during the treatment period and for 8 weeks after treatment is stopped are used to measure blood levels of ribavirin and to determine the effects of ribavirin on the HIV and immune system of the patients.

• Study Type: Interventional
• Enrollment: 42
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane Univ School of Medicine
    • New Orleans, Louisiana, United States, 70112
      • Charity Hosp / Tulane Univ Med School

Participation Criteria

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 be asymptomatic according to the following criteria:

• Normal neurologic exam.
• No unintentional weight loss of greater than 10 lbs. or more than 10 percent of usual body weight within 2 years prior to entering the study.
• No unexplained temperature above 38 degrees C on more than 5 consecutive days or on more than 10 days in any 30 days in the 2 years prior to expected entry into the study.
• No unexplained diarrhea defined by equal to or more than 3 liquid stools per day persisting more than 7 days within 2 years prior to expected entry into the study.
• No active hepatitis of any form. In addition, patients must not have previously had AIDS or an AIDS related illness.

Exclusion Criteria

Co-existing Condition:

Excluded:

• Temperature of greater than 37.8 degrees C.
• Development of an AIDS-defining opportunistic infection.
• Unexplained diarrhea defined by equal to or more than 3 liquid stools per day.
• Active hepatitis of any form.

Patients who have had oral candida infection documented by morphology, or by response to antifungal therapy, or oral hairy leukoplakia, or herpes zoster infection within 2 years of anticipated study entry at any time will be excluded. Patients with a prior history of a malignancy other than cutaneous basal cell carcinomas or cervical carcinoma in situ and patients with a significant chronic underlying medical illness that would impair continuous participation in the study will be excluded.

Prior Medication:

Excluded within 90 days of study entry:

• Immunomodulators.

Active alcohol or drug abuse sufficient in the investigator's opinion to prevent adequate compliance with the study therapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Masking: NONE

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Study Chair: JJ Lertora

Publications and helpful links

General Publications

• Lertora JJ, Rege AB, Lacour JT, Ferencz N, George WJ, VanDyke RB, Agrawal KC, Hyslop NE Jr. Pharmacokinetics and long-term tolerance to ribavirin in asymptomatic patients infected with human immunodeficiency virus. Clin Pharmacol Ther. 1991 Oct;50(4):442-9. doi: 10.1038/clpt.1991.162.

Study record dates

Study Major Dates

• Study Completion (ACTUAL): October 1, 1991

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 3, 2021
• Last Update Submitted That Met QC Criteria: October 27, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Acquired Immunodeficiency Syndrome; Ribavirin; T-Lymphocytes; Administration, Oral; Infusions, Intravenous; Immunologic Surveillance
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immune System Diseases; Slow Virus Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Immunologic Deficiency Syndromes; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Ribavirin
• Other Study ID Numbers: ACTG 035; 11011 (DAIDS ES Registry Number)