A Pilot Study of the Short-Term Effects of Antiretroviral Management Based on Plasma Genotypic Antiretroviral Resistance Testing (GART) Compared With Antiretroviral Management Without Plasma GART

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000874
First received: November 2, 1999
Last updated: September 28, 2013
Last verified: September 2013
  Purpose

To determine the short-term virologic and immunologic effects of using plasma genotypic antiretroviral resistance testing (GART) results (interpreted by study virologists AS PER AMENDMENT 9/17/97) in the management of therapy for antiretroviral-experienced patients failing on one of the following regimens:

  1. zidovudine (ZDV) + (lamivudine) 3TC + (indinavir) IDV
  2. ZDV + 3TC + saquinavir (SQV)
  3. ZDV + 3TC + ritonavir (RTV)
  4. stavudine (d4T) + 3TC + IDV. [AS PER AMENDMENT 11/26/97: To determine the short-term effects of using plasma GART in the management of antiretroviral-experienced patients failing on a triple drug regimen that includes a single protease inhibitor (indinavir [IDV], saquinavir [SQV], ritonavir [RTV], or nelfinavir [NFV]) and two licensed nucleoside reverse transcriptase inhibitors (NRTIs).] A growing body of evidence suggests that antiretroviral resistance is associated with an increased risk of disease progression and death. All commercially available antiretrovirals and many of those in development have been associated with resistance. Fortunately, techniques are available to define HIV genotypic resistance in "real time" as compared to techniques that measure phenotypic resistance that is not practical in a clinical setting. Using genotypic antiretroviral resistance testing (GART) results, along with other currently available markers, may lead to improved treatment decisions compared with using currently available markers alone.

Condition
HIV Infections

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: A Pilot Study of the Short-Term Effects of Antiretroviral Management Based on Plasma Genotypic Antiretroviral Resistance Testing (GART) Compared With Antiretroviral Management Without Plasma GART

Resource links provided by NLM:


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

Biospecimen Retention:   Samples With DNA

Blood collection


Enrollment: 148
Study Start Date: August 1997
Study Completion Date: March 1999
Primary Completion Date: January 1999 (Final data collection date for primary outcome measure)
Groups/Cohorts
1
Participants who are failing a regimen of ZDV, 3TC, and IDV
2
Participants who are failing a regimen of ZDV, 3TC, and SRQ
3
Participants who are failing a regimen of ZDV, 3TC, and RTV
4
Participants who are failing a regimen of d4T, 3TC, and IDV

Detailed Description:

A growing body of evidence suggests that antiretroviral resistance is associated with an increased risk of disease progression and death. All commercially available antiretrovirals and many of those in development have been associated with resistance. Fortunately, techniques are available to define HIV genotypic resistance in "real time" as compared to techniques that measure phenotypic resistance that is not practical in a clinical setting. Using genotypic antiretroviral resistance testing (GART) results, along with other currently available markers, may lead to improved treatment decisions compared with using currently available markers alone.

128 patients are randomized to GART or no GART within each of four strata defined by current antiretroviral regimen:

  1. ZDV plus 3TC plus IDV
  2. ZDV plus 3TC plus SQV
  3. ZDV plus 3TC plus RTV
  4. d4T plus 3TC plus IDV. Each of the four strata contains 22 patients with CD4+ counts of 50 - 199/mm3 and 11 patients with CD4+ counts of 200 - 500/mm3. Upon randomization, clinicians determine a treatment strategy with supplied baseline GART results (GART arm) or without them (no-GART arm). All patients remain on the triple antiretroviral regimen initiated at the randomization visit until at least the 8-week visit. At this time, changes in treatment will be allowed based on an inadequate response to therapy.

[AS PER AMENDMENT 9/17/97: 128 patients are randomized to therapy based on GART results or therapy not based on these results. Patients are stratified into 8 groups defined by current antiretroviral regimen (ZDV/3TC/IDV vs. ZDV/3TC/SQV vs. ZDV/3TC/RTV vs. d4T/3TC/IDV) and screening CD4+ count (50-199 vs. 200-500). Management of patients assigned to the GART group is based on recommendations of study virologists after independent review of patient plasma GART results in addition to current clinical practice. Up to four different treatment regimens using only licensed drugs may be recommended, ranked but considered approximately therapeutically equivalent. The management of patients assigned to the no-GART group is based on current clinical practice and includes only licensed antiretrovirals.] [AS PER AMENDMENT 11/26/97: 160 patients are randomized to GART or no GART within each of 8 strata defined by current antiretroviral regimen (NRTI-1 plus NRTI-2 plus IDV vs. NRTI-1 plus NRTI-2 plus SQV vs. NRTI-1 plus NRTI-2 plus RTV vs. NRTI-1 plus NRTI-2 plus NFV) and screening CD4+ cell count.]

  Eligibility

Ages Eligible for Study:   13 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

HIV-infected participants currently failing their antiretroviral regimens

Criteria

Inclusion Criteria

Patients must have:

  • Documentation of a CD4+ cell count between 50 and 500/mm3 prior to the baseline visit [within 6 weeks prior to baseline visit AS PER AMENDMENT 9/17/97].
  • Documentation of either a plasma HIV RNA > 50,000 copies/ml by the Roche Amplicor HIV-1 assay or > 25,000 copies/ml by the Chiron bDNA assay, performed within 30 days prior to the baseline visit. [AS PER AMENDMENT 9/17/97: Documentation of either a plasma HIV RNA level >20,000 copies/ml by the Roche Amplicor HIV-1 assay or >10,000 copies/ml by the Chiron bDNA assay, performed within 6 weeks prior to baseline visit.]
  • Documentation of a 3-fold rise in plasma HIV RNA level (using the same assay) or a previously documented plasma HIV RNA at an undetectable level while on the current antiretroviral regimen. [AS PER AMENDMENT 9/17/97: Documentation that the screening plasma HIV RNA level is a 3-fold rise from a previous determination (using the same assay) or documentation of a previous plasma HIV RNA <500 copies/ml while on the current antiretroviral regimen.]
  • Signed, informed consent from a parent or legal guardian for patients < 18 years of age.

Prior Medication: Included:

  • At least an 18-month cumulative history of antiretroviral therapy [AS PER AMENDMENT 9/17/97: At least a 12-month cumulative history of antiretroviral therapy].

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions are excluded:

  • Intercurrent illness (which in the clinician's judgment could influence the HIV RNA level) within 2 weeks prior to, or since, obtaining blood for the screening HIV RNA measurement [within 2 weeks prior to obtaining screening HIV RNA specimen or within 2 weeks prior to baseline visit AS PER AMENDMENT 11/26/97].
  • Unwillingness or inability to change antiretroviral therapy.
  • Unwillingness to wait up to 30 days after the GART baseline visit to change current triple treatment therapy regimen [AS PER AMENDMENT 9/17/97: Unwillingness to wait until baseline plasma GART results are available to change the current triple therapy regimen].
  • Accessibility to previous genotypic or phenotypic resistance testing results.
  • Co-enrollment in a clinical trial with anti-HIV drugs.

Concurrent Medication:

Excluded:

  • Agents with anti-HIV activity.
  • Initiation of treatment with IL-2, interferon, or adefovir dipivoxil.
  • Anti-influenza or other vaccines.

Prior Medication:

Excluded:

[AS PER AMENDMENT 11/26/97:

  • Use of immunomodulators within 2 weeks prior to obtaining the screening plasma HIV RNA specimen or within 2 weeks prior to the baseline visit.
  • Use of any anti-HIV agents, other than drugs in the qualifying triple antiretroviral regimen, within the past 16 weeks.]

Patients must currently be on one of the following triple antiretroviral regimens for at least 16 weeks:

  • ZDV + 3TC + IDV
  • ZDV + 3TC + SQV
  • ZDV + 3TC + RTV
  • d4T + 3TC + IDV. [AS PER AMENDMENT 11/26/97: Patients must currently be on a triple antiretroviral regimen that includes a single protease inhibitor (IDV, SQV, RTV, or NFV) and two licensed NRTIs for at least 16 weeks.]

Concurent Treatment: Excluded:

  • Vaccination within 2 weeks prior to, or since, obtaining blood for the screening HIV RNA measurement [within 2 weeks prior to obtaining screening plasma HIV RNA specimen or within 2 weeks prior to the baseline visit AS PER AMENDMENT 11/26/97].
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00000874

Locations
United States, California
Community Consortium of San Francisco
San Francisco, California, United States, 94110
Community Consortium / UCSF
San Francisco, California, United States, 94110
United States, Colorado
Denver CPCRA / Denver Public Hlth
Denver, Colorado, United States, 80204
Alpine Family Medicine / Janowski
Denver, Colorado, United States, 80204
S Denver Infectious Diseases Specialists
Denver, Colorado, United States, 80204
VA Med Ctr
Denver, Colorado, United States, 80204
United States, District of Columbia
Veterans Administration Med Ctr / Regional AIDS Program
Washington, District of Columbia, United States, 20422
Montgomery County Health Dept
Washington, District of Columbia, United States, 20422
United States, Georgia
AIDS Research Consortium of Atlanta
Atlanta, Georgia, United States, 30308
United States, Illinois
AIDS Research Alliance - Chicago
Chicago, Illinois, United States, 60657
United States, Louisiana
Louisiana Comm AIDS Rsch Prog / Tulane Univ Med
New Orleans, Louisiana, United States, 70112
United States, Michigan
Henry Ford Hosp
Detroit, Michigan, United States, 48202
Wayne State Univ / WSU / DMC HIV / AIDS Program
Detroit, Michigan, United States, 48201
United States, New Jersey
Southern New Jersey AIDS Cln Trials / Dept of Med
Camden, New Jersey, United States, 08103
Mercer Area Early Intervention Services
Camden, New Jersey, United States, 08103
North Jersey Community Research Initiative
Newark, New Jersey, United States, 07103
United States, New Mexico
Partners Research
Albuquerque, New Mexico, United States, 87131
T A Ferrill Regional HIV Clinic
Albuquerque, New Mexico, United States, 87131
Partners in Research / New Mexico
Albuquerque, New Mexico, United States, 87131
United States, New York
Harlem AIDS Treatment Group / Harlem Hosp Ctr
New York, New York, United States, 10037
United States, Oregon
The Research and Education Group
Portland, Oregon, United States, 97210
United States, Pennsylvania
Philadelphia FIGHT
Philadelphia, Pennsylvania, United States, 19107
Saint Joseph's Hosp
Philadelphia, Pennsylvania, United States, 19107
United States, Virginia
Richmond AIDS Consortium
Richmond, Virginia, United States, 23298
Sponsors and Collaborators
Investigators
Study Chair: Baxter J
Study Chair: Mayers D
Study Chair: Merigan T
  More Information

Publications:
Mayers D. A Pilot Study of the Short-Term Effects of Antiretroviral Management Based on Plasma Genotypic Antiretroviral Resistance Testing (GART) Compared With Antiretroviral Management Without Plasma GART. (abstract no.124)
Baxter JD, Mayers DL, Wentworth DN, Neaton JD, Merigan TC. A pilot study of the short-term effects of antiretroviral management based on plasma genotypic antiretroviral resistance testing (GART) in patients failing antiretroviral therapy. Conf Retroviruses Opportunistic Infect. 1999 Jan 31-Feb 4;6th:206 (abstract no LB8)

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000874     History of Changes
Other Study ID Numbers: CPCRA 046, 11598
Study First Received: November 2, 1999
Last Updated: September 28, 2013
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
HIV-1
Drug Therapy, Combination
Zidovudine
Stavudine
Drug Resistance, Microbial
HIV Protease Inhibitors
CD4 Lymphocyte Count
Ritonavir
Lamivudine
Indinavir
RNA, Viral
Genotype
Reverse Transcriptase Inhibitors
Anti-HIV Agents
Viral Load

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
HIV Protease Inhibitors
Reverse Transcriptase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on April 21, 2014