Effectiveness of the Early Addition of Abacavir to an Anti-HIV Drug Combination

HIV Infections Clinical Trial

Official title:

A Pilot Study of Early Treatment Intensification of Antiretroviral Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00001132
• Other study ID #: ACTG A5064
• Secondary ID: AACTG A5064
• Status: Completed
• Phase: Phase 2
• First received: January 17, 2000
• Last updated: September 8, 2008
• Start date: November 1999
• Est. completion date: April 2001

Study information

• Verified date: June 2003
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to see if adding 1 drug to an anti-HIV drug combination early in treatment against HIV can lower the viral load (amount of HIV in the blood) to a level so low that it cannot be measured (undetectable). The drug that will be added to a treatment is abacavir (ABC).

Many patients who take 3 anti-HIV drugs together are able to achieve very low viral loads, for example, viral loads below 50 copies/ml. However, some patients taking only 3 drugs are not able to achieve a viral load this low. Doctors hope that, by adding the drug ABC to a current treatment, a viral load below 50 copies/ml can be achieved. Doctors would like to find out if it is effective to start patients on 3 drugs and then add another drug (treatment intensification) if the treatment is not working as well as hoped.

Description:

Combination antiretroviral therapy can offer patients potent suppression of HIV replication and improved immunologic functioning. However, despite aggressive antiretroviral regimens currently in use, only about 50 to 60 percent of patients attain plasma viral loads below 50 copies/ml after 24 weeks. Initiating treatment with a 4-drug regimen may increase this percentage, but this may also contribute to patient non-adherence, drug-related toxicities, potential cross-resistance to drugs used in future regimens, and high financial costs. Another strategy is early intensification (adding a single drug to an existing regimen) in patients who are at risk for attaining incomplete viral suppression after 24 weeks of therapy. ABC may produce a significant antiviral effect when used as an intensification agent in patients on a stable antiretroviral regimen. The results of this study will offer insight into the potential benefits of early treatment intensification.

Patients entering this study will have initiated potent antiretroviral therapy. Between 60 and 90 days [AS PER AMENDMENT 1/9/01: 60 and 104 days] after beginning their background regimen, patients are randomized to add either ABC (Arm A) or a matching placebo (Arm B) for 12 weeks. Patients completing 12 weeks of treatment continue on study for an additional 24 weeks to Week 36. Patients discontinue treatment if virologic failure occurs at any time. Patients still return to the clinic for HIV-1 RNA measurements at Weeks 12 and 36, depending on when discontinuation occurred. Patients who discontinue treatment at or after Week 12 due to virologic failure are offered open-label ABC for the remainder of the study (through Week 36). Blood samples are collected at Weeks 4, 8, 12, 20, 28, and 36. Plasma samples for population sequencing of HIV-1 PR and RT genes are collected on all patients at study entry and at the time of virologic failure. Baseline genotype (presence or absence of PR and RT resistance mutations and number of resistance mutations) is correlated to treatment outcome. Samples from the time of failure are analyzed for the accumulation of additional resistance mutations. [AS PER AMENDMENT 5/5/00: Patients and their primary care physicians will be unblinded to the patient's treatment after the study is completed at Week 36 or if virologic failure occurs at or after Week 12 [AS PER AMENDMENT 1/9/01: or if ABC hypersensitivity is suspected].]

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: April 2001
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 13 Years and older

Eligibility

Inclusion Criteria

Patients may be eligible for this study if they:

• Are HIV-positive.

• Have been taking anti-HIV therapy that includes at least 3 anti-HIV drugs and is an acceptable anti-HIV drug combination for 60 to 104 days before study treatment. Patients must not have changed any of the drugs in the 28 days before study entry. (This study has been changed by extending the number of days that anti-HIV therapy has been received.)

• Have a viral load greater than 500 but less than or equal to 10,000 copies/ml and have had a significant decrease in viral load between 49 and 84 days after starting this anti-HIV therapy. (This study has been changed by extending the length of time of viral load decrease.)

• Are at least 13 years old (consent of parent or guardian required if under 18).

• Agree to practice abstinence or use barrier method of birth control (such as condoms) during the study and for 3 months after.

Exclusion Criteria

Patients will not be eligible for this study if they:

• Have ever taken ABC.

• Have received anti-HIV therapy for more than 104 days in the past. (This study has been changed by extending the number of days that anti-HIV therapy has been received.)

• Have a fever for 7 days in the 30 days before study entry.

• Have cancer, including Kaposi's sarcoma, that requires chemotherapy.

• Have an active infection that requires treatment in the 21 days before study entry.

• Have any opportunistic (AIDS-related) infection or disease that requires a change in medication in the 14 days before study entry.

• Have any medical condition or history of an illness that the doctor feels would place them at risk or make them unable to complete the study.

• Are taking drugs that affect the immune system or any experimental anti-HIV drugs, except for their current drug combination.

• Are taking St. John's wort. (This study has been changed. Previously, patients taking St. John's wort were eligible.)

• Have received a vaccine in the 21 days before study entry.

• Are pregnant or breast-feeding.

Study Design

Endpoint Classification: Safety Study, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• Abacavir sulfate

Locations

Country	Name	City	State
Puerto Rico	Univ of Puerto Rico	San Juan
United States	Emory Univ	Atlanta	Georgia
United States	Johns Hopkins Hosp	Baltimore	Maryland
United States	State of MD Div of Corrections / Johns Hopkins Univ Hosp	Baltimore	Maryland
United States	SUNY / Erie County Med Ctr at Buffalo	Buffalo	New York
United States	Univ of North Carolina	Chapel Hill	North Carolina
United States	Cook County Hosp	Chicago	Illinois
United States	Northwestern Univ Med School	Chicago	Illinois
United States	Univ of Cincinnati	Cincinnati	Ohio
United States	Univ of Texas, Southwestern Med Ctr of Dallas	Dallas	Texas
United States	Univ of Colorado Health Sciences Ctr	Denver	Colorado
United States	Duke Univ Med Ctr	Durham	North Carolina
United States	UCLA CARE Ctr	Los Angeles	California
United States	Willow Clinic	Menlo Park	California
United States	Univ of Miami School of Medicine	Miami	Florida
United States	Vanderbilt Univ Med Ctr	Nashville	Tennessee
United States	Aaron Diamond AIDS Rsch Ctr / Rockefeller Univ	New York	New York
United States	Bellevue Hosp / New York Univ Med Ctr	New York	New York
United States	Beth Israel Med Ctr	New York	New York
United States	Columbia Presbyterian Med Ctr	New York	New York
United States	Philadelphia Veterans Administration Med Ctr	Philadelphia	Pennsylvania
United States	Univ of Pennsylvania at Philadelphia	Philadelphia	Pennsylvania
United States	Univ of Rochester Medical Center	Rochester	New York
United States	Santa Clara Valley Med Ctr / AIDS Community Rsch Consortium	San Jose	California
United States	Univ of Washington	Seattle	Washington
United States	St Louis Regional Hosp / St Louis Regional Med Ctr	St Louis	Missouri
United States	San Mateo AIDS Program / Stanford Univ	Stanford	California
United States	Stanford Univ Med Ctr	Stanford	California
United States	Harbor UCLA Med Ctr	Torrance	California
United States	Julio Arroyo	West Columbia	South Carolina

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Countries where clinical trial is conducted

United States,  Puerto Rico, 

References & Publications (1)

Bartlett JA, Tebas P, Bassett R, Huang W, Kuritzkes D, Reisler R, Loyack N, Robison K; ACTG A5064 Team. Early intensification with abacavir in subjects at high risk for incomplete viral suppression. Antivir Ther. 2003 Aug;8(4):361-3. — View Citation

External Links

•   Click here for more information about abacavir sulfate
•   Haga clic aquí para ver información sobre este ensayo clínico en español.