A Comparison of Two Tests for Anti-HIV Drug Resistance

HIV-1 Resistance Testing During Antiretroviral Failure: Comparison of Sequencing Versus Phenotyping

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.

Study Overview

• Status: Completed
• Conditions: HIV Infections

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.

• Study Type: Observational
• Enrollment: 600

Contacts and Locations

Study Locations

• Puerto Rico
  • San Juan, Puerto Rico, 009365067
    • Univ of Puerto Rico
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Univ of Alabama at Birmingham
  • California
    • Los Angeles, California, United States, 90095
      • UCLA CARE Ctr
    • Los Angeles, California, United States, 900331079
      • Univ of Southern California / LA County USC Med Ctr
    • Menlo Park, California, United States, 94025
      • Willow Clinic
    • San Francisco, California, United States, 94110
      • Univ of California San Francisco
    • San Francisco, California, United States, 941104206
      • University of California San Francisco
    • San Jose, California, United States, 951282699
      • Santa Clara Valley Med Ctr / AIDS Community Rsch Consortium
    • Stanford, California, United States, 943055107
      • San Mateo AIDS Program / Stanford Univ
    • Stanford, California, United States, 943055107
      • Stanford Univ Med Ctr
    • Torrance, California, United States, 90502
      • Harbor UCLA Med Ctr
  • Colorado
    • Denver, Colorado, United States, 80262
      • Univ of Colorado Health Sciences Ctr
    • Denver, Colorado, United States, 80262
      • Denver Dept of Health and Hosps
  • Florida
    • Miami, Florida, United States, 331361013
      • Univ of Miami School of Medicine
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Emory Univ
  • Hawaii
    • Honolulu, Hawaii, United States, 96816
      • Univ of Hawaii
  • Illinois
    • Chicago, Illinois, United States, 60612
      • The CORE Ctr
    • Chicago, Illinois, United States, 60611
      • Northwestern Univ Med School
    • Chicago, Illinois, United States, 60612
      • Rush Presbyterian - Saint Luke's Med Ctr
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Hosp
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Harvard (Massachusetts Gen Hosp)
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess - West Campus
    • Boston, Massachusetts, United States, 02215
      • Brigham and Women's Hosp
  • New York
    • Buffalo, New York, United States, 14215
      • SUNY / Erie County Med Ctr at Buffalo
    • New York, New York, United States, 10003
      • Beth Israel Med Ctr
    • New York, New York, United States, 10021
      • Cornell Univ Med Ctr
    • New York, New York, United States, 10016
      • Bellevue Hosp / New York Univ Med Ctr
    • New York, New York, United States, 10029
      • Mount Sinai Med Ctr
    • New York, New York, United States, 10032
      • Columbia Presbyterian Med Ctr
    • New York, New York, United States, 10011
      • Cornell Clinical Trials Unit - Chelsea Clinic
  • North Carolina
    • Chapel Hill, North Carolina, United States, 275997215
      • Univ of North Carolina
    • Charlotte, North Carolina, United States, 28203
      • Carolinas Med Ctr
    • Durham, North Carolina, United States, 27710
      • Duke Univ Med Ctr
    • Greensboro, North Carolina, United States, 27401
      • Moses H Cone Memorial Hosp
  • Ohio
    • Cincinnati, Ohio, United States, 452670405
      • Univ of Cincinnati
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve Univ
    • Cleveland, Ohio, United States, 441091998
      • MetroHealth Med Ctr
    • Columbus, Ohio, United States, 432101228
      • Ohio State Univ Hosp Clinic
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Univ of Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Philadelphia Veterans Administration Med Ctr
    • Pittsburgh, Pennsylvania, United States, 15213
      • Univ of Pittsburgh
  • Rhode Island
    • Providence, Rhode Island, United States, 02906
      • Brown Univ / Miriam Hosp
    • Providence, Rhode Island, United States, 02906
      • Miriam Hosp / Brown Univ
  • South Carolina
    • West Columbia, South Carolina, United States, 29169
      • Julio Arroyo
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Vanderbilt Univ Med Ctr
  • Texas
    • Dallas, Texas, United States, 75390
      • Univ of Texas, Southwestern Med Ctr of Dallas
  • Washington
    • Seattle, Washington, United States, 98104
      • Univ of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Study Chair: Richard D'Aquila; Study Chair: Daniel Kuritzkes

Study record dates

Study Registration Dates

• First Submitted: November 8, 2000
• First Submitted That Met QC Criteria: August 30, 2001
• First Posted (Estimate): August 31, 2001

Study Record Updates

• Last Update Posted (Estimate): September 25, 2008
• Last Update Submitted That Met QC Criteria: September 24, 2008
• Last Verified: July 1, 2004

More Information

Terms related to this study

• Keywords: Anti-HIV Agents; HIV-1; Genotype; Phenotype; Drug Resistance, Microbial; Microbial Sensitivity Tests; Sequence Analysis, DNA
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections
• Other Study ID Numbers: ACTG A5076; AACTG A5076