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

This study has been completed.
Sponsor:
Information provided by:
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00001132
First received: January 17, 2000
Last updated: September 8, 2008
Last verified: June 2003
  Purpose

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.


Condition Intervention Phase
HIV Infections
Drug: Abacavir sulfate
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: A Pilot Study of Early Treatment Intensification of Antiretroviral Therapy

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 80
Study Start Date: November 1999
Estimated Study Completion Date: April 2001
Detailed 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].]

  Eligibility

Ages Eligible for Study:   13 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00001132

  Show 30 Study Locations
Sponsors and Collaborators
Investigators
Study Chair: John Bartlett
Study Chair: Pablo Tebas
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT00001132     History of Changes
Other Study ID Numbers: ACTG A5064, AACTG A5064
Study First Received: January 17, 2000
Last Updated: September 8, 2008
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Placebos
HIV-1
Drug Therapy, Combination
RNA, Viral
Reverse Transcriptase Inhibitors
Anti-HIV Agents
Viral Load
abacavir

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Reverse Transcriptase Inhibitors
Abacavir
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on July 22, 2014