A Study to Compare The Ability of Different Anti-HIV Drugs to Decrease Viral Load After Nelfinavir (an Anti-HIV Drug)Treatment Failure

NCT ID: NCT00000918

Last Updated: 2012-05-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 300 participants
• Study Classification: INTERVENTIONAL
• Study Completion Date: 2002-02-28

Brief Summary

The purpose of this study is to determine the safety and effectiveness of combining several anti-HIV drugs in order to decrease plasma viral load (level of HIV in the blood) in HIV-positive patients who have failed nelfinavir (NFV) treatment.

In order to determine the ability of a drug regimen to decrease viral load after drug treatment has failed, it is best to test a variety different of drug "cocktails" (drug regimens). The drug cocktails in this study include 2 new nucleoside reverse transcriptase inhibitors (NRTIs), efavirenz (an NNRTI, non-nucleoside reverse transcriptase inhibitor), and either 1 or 2 protease inhibitors. It is important to include multiple drugs from different groups in a drug cocktail since combinations containing fewer drugs are likely to fail.

Detailed Description

To maximize the likelihood of a favorable response to salvage therapy, 4 or 5 drug regimens should be studied. Regimens containing fewer drugs, particularly those lacking a non-nucleoside reverse transcriptase inhibitor (NNRTI) such as efavirenz, are likely to result in an unacceptable rate of virological failure. Therefore, this study examines drug combinations which include two new nucleoside reverse transcriptase inhibitors (NRTIs), the NNRTI efavirenz, and either one or two protease inhibitors which are known not to produce cross-resistance to nelfinavir.

Patients are randomly selected to receive 1 of the following 4 treatment regimens:

Arm A: Ritonavir, saquinavir, efavirenz, and 2 new NRTIs. Arm B: Indinavir, efavirenz and 2 new NRTIs. Arm C: Amprenavir, efavirenz, and 2 new NRTIs. [AS PER AMENDMENT 3/22/00: Patients have the option to increase the APV dose or to add low-dose ritonavir. APV will continue to be provided by the study; ritonavir will not be provided by the study.] Arm D: Indinavir, amprenavir, efavirenz, and 2 new NRTIs. [AS PER AMENDMENT 6/28/99: All treatment regimens must include at least 1 new NRTI.] [AS PER AMENDMENT 3/22/00: ACTG 400 will continue to provide originally randomized study medications to all patients until approximately May 10, 2000, regardless of virologic response. Patients may also add antiretrovirals of their choice to this regimen (not provided by the study).] Clinical assessments are taken at Weeks 2, 4, 8, 12, 16, and every 8 weeks thereafter for the duration of the study. In addition, 2 substudies are being conducted: a drug-interaction substudy and a drug-exposure substudy. [AS PER AMENDMENT 3/22/00: Both substudies are closed to accrual and their pharmacokinetics assessments are discontinued.]

Conditions

HIV Infections

Study Design

• Primary Study Purpose: TREATMENT

Interventions

Indinavir sulfate

Intervention Type: DRUG

Lamivudine/Zidovudine

Intervention Type: DRUG

Ritonavir

Intervention Type: DRUG

Amprenavir

Intervention Type: DRUG

Efavirenz

Intervention Type: DRUG

Saquinavir

Intervention Type: DRUG

Lamivudine

Intervention Type: DRUG

Stavudine

Intervention Type: DRUG

Zidovudine

Intervention Type: DRUG

Didanosine

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

Patients may be eligible for this study if they:

• Are over 13 years old (need consent of parent or guardian if under 18).
• Are HIV-positive.
• Currently have virologic failure (more than 1,000 copies of HIV RNA per ml).
• Agree to abstinence or use of effective birth control during the study.
• Have been taking NFV for the past 12 weeks.

Exclusion Criteria

Patients will not be eligible for this study if they:

• Have a fever for 7 days or diarrhea for 30 days before study entry.
• Have a history of peripheral neuropathy within 60 days of study entry.
• Have hepatitis.
• Have any malignancy (cancer) other than minimal Kaposi's sarcoma.
• Are pregnant or breast-feeding.
• Are receiving radiation, chemotherapy, or any therapy for any illness within 14 days of study entry.
• Have taken amprenavir, saquinavir, indinavir or ritonavir for more than 7 days.
• Have received an HIV vaccine 30 days before study entry.
• Are receiving certain other 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

John Mellors; William Powderly

Role: STUDY_CHAIR

Scott Hammer

Role: STUDY_CHAIR

Locations

Univ of Alabama at Birmingham

Birmingham, Alabama, United States

Univ of Southern California / LA County USC Med Ctr

Los Angeles, California, United States

UCLA CARE Ctr

Los Angeles, California, United States

Willow Clinic

Menlo Park, California, United States

San Francisco AIDS Clinic / San Francisco Gen Hosp

San Francisco, California, United States

San Francisco Gen Hosp

San Francisco, California, United States

Santa Clara Valley Med Ctr / AIDS Community Rsch Consortium

San Jose, California, United States

Marin County Specialty Clinic

San Rafael, California, United States

San Mateo AIDS Program / Stanford Univ

Stanford, California, United States

Stanford Univ Med Ctr

Stanford, California, United States

Univ of Colorado Health Sciences Ctr

Denver, Colorado, United States

Howard Univ

Washington D.C., District of Columbia, United States

Univ of Miami School of Medicine

Miami, Florida, United States

Emory Univ

Atlanta, Georgia, United States

Northwestern Univ Med School

Chicago, Illinois, United States

Cook County Hosp

Chicago, Illinois, United States

Rush Presbyterian - Saint Luke's Med Ctr

Chicago, Illinois, 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

St Louis Regional Hosp / St Louis Regional Med Ctr

St Louis, Missouri, United States

SUNY / Erie County Med Ctr at Buffalo

Buffalo, New York, 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

Mount Sinai 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

Duke Univ Med Ctr

Durham, North Carolina, United States

Univ of Cincinnati

Cincinnati, Ohio, United States

Case Western Reserve Univ

Cleveland, Ohio, United States

Ohio State Univ Hosp Clinic

Columbus, Ohio, United States

Univ of Pennsylvania at Philadelphia

Philadelphia, Pennsylvania, United States

Julio Arroyo

West Columbia, South Carolina, United States

Univ of Washington

Seattle, Washington, United States

Univ of Puerto Rico

San Juan, , Puerto Rico

Countries

United States; Puerto Rico

Other Identifiers

11356

Identifier Type: REGISTRY

Identifier Source: secondary_id

Substudy A5013s

Identifier Type: -

Identifier Source: secondary_id

Substudy A5022s

Identifier Type: -

Identifier Source: secondary_id

ACTG 400

Identifier Type: -

Identifier Source: org_study_id