A Study to Demonstrate That Anti-HIV Drug Therapy Can be Stopped Without Causing Viral Resistance, and to Characterize Drug Elimination From the Body

July 29, 2008 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

A Phase II Study to Demonstrate That Therapy With Efavirenz (EFV) and Other Antiretroviral Drugs Can Be Interrupted Without Selecting for EFV-Resistant Virus, and Relation to Kinetics of Drug Elimination

The purpose of this study is to find out if anti-HIV drugs can be stopped without the virus becoming resistant to the drugs. The study will also examine how fast anti-HIV drugs leave the body.

Not all HIV-infected patients may require continuous and indefinite anti-HIV therapy. There is evidence that stopping anti-HIV therapy will not make the virus resistant to efavirenz (EFV), an anti-HIV drug that remains in the body longer than most treatment drugs. In another study, patients were treated with EFV, zidovudine (ZDV), and lamivudine (3TC). The patients' virus was controlled despite the fact that some patients missed medication dosages. Many patients stop anti-HIV therapy because of negative effects. This study will examine the body's ability to fight and control virus in patients who stop therapy.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The concept that all patients with HIV-1 infection require continuous and indefinite antiretroviral therapy (ART) has been questioned. There are both theoretical reasons and supporting empiric evidence that suggest that discontinuing ART should not select for EFV-resistance. In Dupont Protocol 006, antiretroviral-naive patients were randomized to receive EFV, ZDV, and 3TC. This regimen was associated with an excellent and sustained virologic response. It is certain that many patients in this study were able to maintain sustained suppression of HIV-1 RNA to below limits of detection despite missing occasional doses of all medications. Since therapy with ZDV and 3TC alone is unlikely to maintain virologic control, emergence of substantial high-level EFV resistance should have led to virologic failure. The fact that there were relatively few virologic failures in that study provides indirect but strong evidence that simultaneous discontinuation of EFV, ZDV, and 3TC is unlikely to be associated with emergence of EFV resistance. Many individuals discontinue antiretroviral therapy because of adverse effects. This study provides the opportunity to determine whether the virologic response of patients who discontinue antiretroviral therapy will be compromised.

Participants will discontinue their EFV. Other antiretroviral drugs in the patients' regimens may be continued for up to three days after the last EFV dose. Patients will not resume EFV or other antiretroviral agents for at least 28 days after stopping EFV, unless the CD4 cell count declines to a level that indicates the need to resume therapy. Throughout the study, patients will have blood drawn on specified days for plasma EFV assays, intracellular NRTI-TP assays, and demonstration of EFV resistance. After patients have been off their antiretrovirals for at least four weeks, they may choose to restart their ART, start a new regimen, or discontinue their ART. Patients who restart their ART need to come to the clinic seven days after restarting to have blood drawn. After plasma EFV assays have been completed and HIV resistance has not been demonstrated, three patients will have a clonal analysis performed.

Study Type

Interventional

Enrollment

36

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
      • San Francisco, California, United States, 94110
        • San Francisco General Hosp
    • Colorado
      • Denver, Colorado, United States, 80262
        • Univ of Colorado Health Sciences Ctr
    • Ohio
      • Cincinnati, Ohio, United States, 452670405
        • Univ of Cincinnati
    • Rhode Island
      • Providence, Rhode Island, United States, 02906
        • Stanley Street Treatment and Resource
      • Providence, Rhode Island, United States, 02906
        • Rhode Island Hosp
      • Providence, Rhode Island, United States, 02906
        • The Miriam Hosp
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Comprehensive Care Clinic

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 may be eligible for this study if they:

  • Are at least 18 years old.
  • Are on EFV and at least 2 other anti-HIV drugs.
  • Are HIV-infected.
  • Have a CD4 cell count greater than 350 cells/mm3 within 21 days of study entry.
  • Have a viral load less than 50 copies/ml within 21 days of study entry.
  • Have an estimated creatinine clearance greater than 30 ml/minute within 21 days of study entry.
  • Have a negative pregnancy test if female. All patients able to have children must agree not to become pregnant or to impregnate or agree to use 2 reliable methods of contraception, including a barrier method.
  • Are planning to stop anti-HIV drugs as part of another study, not solely to participate in this study.
  • (This study has been changed. In an earlier version, EFV plus lamivudine plus zidovudine or stavudine was required.)

Exclusion Criteria

Patients may not be eligible for this study if they:

  • Had a serious illness and have not finished therapy for the illness or become stable on the therapy.
  • Abuse alcohol or drugs.
  • Have taken any nonnucleoside reverse transcriptase inhibitor other than EFV.
  • (This study has been changed. In an earlier version, patients were ineligible if they had taken certain anti-HIV agents or stopped treatment for more than 7 days in a row before the study.)

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: None (Open Label)

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: David Haas

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 Registration Dates

First Submitted

January 10, 2002

First Submitted That Met QC Criteria

January 10, 2002

First Posted (Estimate)

January 11, 2002

Study Record Updates

Last Update Posted (Estimate)

July 30, 2008

Last Update Submitted That Met QC Criteria

July 29, 2008

Last Verified

January 1, 2005

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ACTG A5131

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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