A Study to Compare the Effectiveness of Different Anti-HIV Drug Regimens in Keeping Levels of HIV in the Blood as Low as Possible

NCT ID: NCT00000939

Last Updated: 2021-10-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Completion Date: 2000-01-31

Brief Summary

This study will look at different anti-HIV drug regimens to see which works best to keep the level of HIV (viral load) in the blood as low as possible during maintenance therapy. You will be assigned randomly (like tossing a coin) to 1 of 3 groups:

Group 1: Didanosine plus stavudine plus hydroxyurea (ddI/d4T/HU). Group 2: Didanosine plus stavudine plus efavirenz (ddI/d4T/EFV). Group 3: This group of patients will remain on their current drug regimens. This study will last approximately 3 years; you will receive study medications for the duration of the study.

Anti-HIV drug regimens that include protease inhibitors (PIs) are very good at lowering viral load. However, some patients have a rise in HIV levels while on PI maintenance. It may be possible to keep HIV levels low using another class of drugs for maintenance that are easier to take and less expensive than PIs. If viral load increases while a patient is taking this second group of drugs, it may be possible to restart the PI drug regimen and again decrease HIV levels.

Detailed Description

Combination antiretroviral therapies using protease inhibitors (PIs) are capable of suppressing plasma HIV RNA to undetectable levels. However, approximately 10% of patients who achieve undetectable viral loads will experience a detectable rise in HIV RNA each year. When HIV replication has been suppressed to very low levels, it may be possible to consolidate antiretroviral therapy into a simpler and potentially less toxic "maintenance" regimen without a PI. Such a regimen would ideally be potent enough to continue to maintain viral suppression but use agents that are better tolerated, more easily salvaged, less expensive, and/or more convenient than PI-containing regimens. Subsequent rises in HIV viremia with non-PI maintenance regimens may respond to resumption of the pre-maintenance PI-containing regimen, extending the use of the potent PI class.

Patients are randomized 1:1:1 to treatment with ddI/d4T/HU (Arm A) versus ddI/d4T/EFV (Arm B) versus continuation of the pre-entry PI-containing regimen (Arm C). Viral load is measured at Weeks 1, 2, 4, 8, 12, 16, 20, and 24, then every 8 weeks for up to 3 years. Upon virologic failure (plasma HIV RNA greater than or equal to 200 copies/ml), or drug intolerance, patients on the maintenance regimens (Arms A and B) restart their pre-entry PI-containing regimen. Patients on Arm C are managed according to best medical judgment of their primary care provider in the event of virologic failure.

Conditions

HIV Infections

Keywords

Didanosine; Drug Therapy, Combination; Stavudine; HIV Protease Inhibitors; Hydroxyurea; RNA, Viral; Reverse Transcriptase Inhibitors; Anti-HIV Agents; Viral Load; efavirenz

Study Design

• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

Hydroxyurea

Intervention Type: DRUG

Efavirenz

Intervention Type: DRUG

Stavudine

Intervention Type: DRUG

Didanosine

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

You may be eligible for this study if you:

• Are at least 13 years old (need consent if under 18).
• Are HIV-positive.
• Are taking your first anti-HIV drug regimen, which must include a PI and at least one NRTI (nucleoside reverse transcriptase inhibitor) and have been on this regimen for at least 12 months.
• Have a viral load less than 400 copies/ml for at least 12 months prior to study entry, and have a viral load less than 50 copies/ml within 60 days of study entry.
• Have a CD4 cell count of at least 200 cells/mm3 within 60 days of study entry.
• Are willing to go back on the drugs you are currently on, if necessary.
• Are willing to use effective methods of birth control during the study and for 3 months after.

Exclusion Criteria

You will not be eligible for this study if you:

• Have taken ddI, d4T, or HU for more than 2 weeks.
• Have taken any NNRTI (non-nucleoside reverse transcriptase inhibitor) for more than 7 days.
• Have ever taken EFV.
• Have received an HIV vaccine within 30 days prior to study entry.
• Have an AIDS-related cancer that requires chemotherapy.
• Have or have had pancreatic disease.
• Are being treated for a significant illness.
• Abuse drugs or alcohol.
• Are pregnant or breast-feeding.
• Are allergic to any study drugs.
• Have received certain medications.

• Minimum Eligible Age: 13 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David Wohl

Role: STUDY_CHAIR

Joe Eron

Role: STUDY_CHAIR

Roy Gulick

Role: STUDY_CHAIR

Locations

Willow Clinic

Menlo Park, California, United States

Santa Clara Valley Med Ctr / AIDS Community Rsch Consortium

San Jose, California, United States

San Mateo AIDS Program / Stanford Univ

Stanford, California, United States

Stanford Univ Med Ctr

Stanford, California, United States

Univ of Miami School of Medicine

Miami, Florida, United States

Indiana Univ Hosp

Indianapolis, Indiana, United States

Division of Inf Diseases/ Indiana Univ Hosp

Indianapolis, Indiana, United States

Methodist Hosp of Indiana / Life Care Clinic

Indianapolis, Indiana, United States

Harvard (Massachusetts Gen Hosp)

Boston, Massachusetts, United States

Beth Israel Deaconess - West Campus

Boston, Massachusetts, United States

Beth Israel Med Ctr

New York, New York, United States

Bellevue Hosp / New York Univ Med Ctr

New York, New York, United States

Chelsea Ctr

New York, New York, United States

Cornell Univ Med Ctr

New York, New York, United States

Univ of Rochester Medical Center

Rochester, New York, United States

Univ of North Carolina

Chapel Hill, North Carolina, United States

Univ of Cincinnati

Cincinnati, Ohio, United States

Ohio State Univ Hosp Clinic

Columbus, Ohio, United States

Univ of Pennsylvania at Philadelphia

Philadelphia, Pennsylvania, United States

Countries

United States

Other Identifiers

10885

Identifier Type: REGISTRY

Identifier Source: secondary_id

ACTG A5039

Identifier Type: -

Identifier Source: secondary_id

A5039

Identifier Type: -

Identifier Source: org_study_id