Clinical trial NCT00006490: A Comparison of Two Tests for Anti-HIV Drug Resistance
Official title: HIV-1 Resistance Testing During Antiretroviral Failure: Comparison of Sequencing Versus Phenotyping
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: HIV Infections
Keywords: HIV-1
Drug Resistance, Microbial
Sequence Analysis, DNA
Microbial Sensitivity Tests
Genotype
Phenotype
Anti-HIV Agents
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2001-08-31
Enrollment: 600
Sex: ALL
Minimum age (years): 14
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no

Brief summary: The purpose of this study is to compare 2 different types of tests of the HIV virus to see which specific anti-HIV drugs would work the best.

Drug resistance is a major reason for therapy failure in HIV patients. Two types of tests can detect resistance to drugs: 1) genotyping (sequencing), which looks at the DNA sequence of a virus to see whether it has developed any genetic resistance; 2) phenotyping, which looks at the ability of different drugs to suppress virus growth in the laboratory. Genotyping and phenotyping can help doctors give patients the most effective drug therapy.

Detailed description: The emergence of drug resistance is a major factor contributing to the failure of antiretroviral therapy in HIV-infected patients. Drug resistance can be detected by genotypic or phenotypic assays, both having distinct advantages and disadvantages. Results from genotypic and phenotypic testing are helpful in excluding from the subsequent regimen drugs to which the resistance is identified, and both tests predict virologic response to salvage therapy in patients who have failed a previous regimen. Resistance testing is likely to be beneficial as an aid in selecting a salvage regimen.

At entry, patients are randomized to Arm A (sequencing) or Arm B (phenotyping) and have a resistance test drawn while still receiving the current regimen even though regimen failure is suspected. The test results are available between Weeks 1 and 4, inclusive. There are weekly visits for the first 4 weeks after entry to monitor viral load and maintenance of the current failing (prestudy) regimen. If virologic failure is confirmed, a new regimen is chosen and prescribed at the first visit after resistance test results are available. \[AS PER AMENDMENT 12/6/00: If the resistance assay fails to yield results, another regimen is chosen and prescribed based on the patient's medical and medication history.\] If virologic failure is not confirmed, the current drug regimen is not changed. Otherwise, on-site study visits occur every 4 weeks until Week 24 and then every 8 weeks thereafter through Week 48. \[AS PER AMENDMENT 12/6/00: on-site study visits occur every 4 weeks until Week 24 and then every 8 weeks thereafter\]. Medical resource use is assessed at baseline and then every 8 weeks through Week 48. Quality of life is assessed at baseline and then every 16 weeks through Week 48.

Eligibility criteria: Inclusion Criteria

Patients may be eligible for this study if they:

* Are HIV-positive.
* Have failed 2 to 4 anti-HIV regimens containing 3 or more combinations of drugs. A patient has failed his/her current regimen if he/she has, within 30 days of study entry, either a viral load (level of HIV in the blood) of at least 10,000 copies/ml or 2 tests which show a viral load between 1,000 and 10,000 copies/ml.
* Have taken 3 or more anti-HIV drugs for 8 or more weeks before the study.
* Are at least 14 years old.
* Have consent of parent or guardian if less than 18 years old.

Exclusion Criteria

Patients will not be eligible for this study if they:

* Have failed only 1 anti-HIV drug combination.
* Have failed 5 or more anti-HIV drug combinations, each containing 3 to 5 drugs.
* Have had and received the results of prior resistance tests.
* Have had treatment with a combination of 6 or more anti-HIV drugs.
* Have problems absorbing food in the intestine.
* Have had HIV vaccines.
* Have taken drugs that affect the immune system or investigational drugs.
* Are taking medications not allowed with protease inhibitors (PIs) if PIs would be part of their anti-HIV treatment during the study.
* Have failed anti-HIV therapy due to nonadherence to medication.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Univ of Alabama at Birmingham
state: Alabama
city: Los Angeles
country: United States
facility: Univ of Southern California / LA County USC Med Ctr
state: California
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 Francisco
country: United States
facility: University of California San Francisco
state: California
city: San Francisco
country: United States
facility: Univ of California San Francisco
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: Denver Dept of Health and Hosps
state: Colorado
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: Honolulu
country: United States
facility: Univ of Hawaii
state: Hawaii
city: Chicago
country: United States
facility: Northwestern Univ Med School
state: Illinois
city: Chicago
country: United States
facility: Rush Presbyterian - Saint Luke's Med Ctr
state: Illinois
city: Chicago
country: United States
facility: The CORE Ctr
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins Hosp
state: Maryland
city: Boston
country: United States
facility: Harvard (Massachusetts Gen Hosp)
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess - West Campus
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hosp
state: Massachusetts
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: Cornell Clinical Trials Unit - Chelsea Clinic
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: Cornell Univ Med Ctr
state: New York
city: New York
country: United States
facility: Mount Sinai Med Ctr
state: New York
city: New York
country: United States
facility: Columbia Presbyterian Med Ctr
state: New York
city: Chapel Hill
country: United States
facility: Univ of North Carolina
state: North Carolina
city: Charlotte
country: United States
facility: Carolinas Med Ctr
state: North Carolina
city: Durham
country: United States
facility: Duke Univ Med Ctr
state: North Carolina
city: Greensboro
country: United States
facility: Moses H Cone Memorial Hosp
state: North Carolina
city: Cincinnati
country: United States
facility: Univ of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: Case Western Reserve Univ
state: Ohio
city: Cleveland
country: United States
facility: MetroHealth Med Ctr
state: Ohio
city: Columbus
country: United States
facility: Ohio State Univ Hosp Clinic
state: Ohio
city: Philadelphia
country: United States
facility: Philadelphia Veterans Administration Med Ctr
state: Pennsylvania
city: Philadelphia
country: United States
facility: Univ of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Univ of Pittsburgh
state: Pennsylvania
city: Providence
country: United States
facility: Brown Univ / Miriam Hosp
state: Rhode Island
city: Providence
country: United States
facility: Miriam Hosp / Brown Univ
state: Rhode Island
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: Richard D'Aquila
role: STUDY_CHAIR
name: Daniel Kuritzkes
role: STUDY_CHAIR
References: