Clinical trial NCT00001132: Effectiveness of the Early Addition of Abacavir to an Anti-HIV Drug Combination
Official title: A Pilot Study of Early Treatment Intensification of Antiretroviral Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infections
Keywords: Placebos
HIV-1
Drug Therapy, Combination
RNA, Viral
Reverse Transcriptase Inhibitors
Anti-HIV Agents
Viral Load
abacavir
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2001-08-31
Enrollment: 80
Sex: ALL
Minimum age (years): 13
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief 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.

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 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.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA CARE Ctr
state: California
city: Menlo Park
country: United States
facility: Willow Clinic
state: California
city: San Jose
country: United States
facility: Santa Clara Valley Med Ctr / AIDS Community Rsch Consortium
state: California
city: Stanford
country: United States
facility: San Mateo AIDS Program / Stanford Univ
state: California
city: Stanford
country: United States
facility: Stanford Univ Med Ctr
state: California
city: Torrance
country: United States
facility: Harbor UCLA Med Ctr
state: California
city: Denver
country: United States
facility: Univ of Colorado Health Sciences Ctr
state: Colorado
city: Miami
country: United States
facility: Univ of Miami School of Medicine
state: Florida
city: Atlanta
country: United States
facility: Emory Univ
state: Georgia
city: Chicago
country: United States
facility: Northwestern Univ Med School
state: Illinois
city: Chicago
country: United States
facility: Cook County Hosp
state: Illinois
city: Baltimore
country: United States
facility: State of MD Div of Corrections / Johns Hopkins Univ Hosp
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins Hosp
state: Maryland
city: St Louis
country: United States
facility: St Louis Regional Hosp / St Louis Regional Med Ctr
state: Missouri
city: Buffalo
country: United States
facility: SUNY / Erie County Med Ctr at Buffalo
state: New York
city: New York
country: United States
facility: Beth Israel Med Ctr
state: New York
city: New York
country: United States
facility: Bellevue Hosp / New York Univ Med Ctr
state: New York
city: New York
country: United States
facility: Aaron Diamond AIDS Rsch Ctr / Rockefeller Univ
state: New York
city: New York
country: United States
facility: Columbia Presbyterian Med Ctr
state: New York
city: Rochester
country: United States
facility: Univ of Rochester Medical Center
state: New York
city: Chapel Hill
country: United States
facility: Univ of North Carolina
state: North Carolina
city: Durham
country: United States
facility: Duke Univ Med Ctr
state: North Carolina
city: Cincinnati
country: United States
facility: Univ of Cincinnati
state: Ohio
city: Philadelphia
country: United States
facility: Philadelphia Veterans Administration Med Ctr
state: Pennsylvania
city: Philadelphia
country: United States
facility: Univ of Pennsylvania at Philadelphia
state: Pennsylvania
city: West Columbia
country: United States
facility: Julio Arroyo
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt Univ Med Ctr
state: Tennessee
city: Dallas
country: United States
facility: Univ of Texas, Southwestern Med Ctr of Dallas
state: Texas
city: Seattle
country: United States
facility: Univ of Washington
state: Washington
city: San Juan
country: Puerto Rico
facility: Univ of Puerto Rico
Study officials:
name: John Bartlett
role: STUDY_CHAIR
name: Pablo Tebas
role: STUDY_CHAIR
References:
citation: 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. No abstract available.