Using Drug Levels and Drug Resistance Testing to Select Effective Anti-HIV Drug Combinations in Patients With Drug-resistant HIV

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00027339
First received: December 4, 2001
Last updated: May 17, 2012
Last verified: May 2012
  Purpose

Because people infected with HIV strains that are resistant to anti-HIV drugs have fewer effective treatment options, selecting an effective anti-HIV drug combination is difficult. A combination of protease inhibitors (PIs), when added to a patient's current anti-HIV therapy, may decrease viral load and increase drug activity. Tests that measure drug levels in the blood and tests to evaluate the drug resistance of HIV may also be helpful in choosing the best anti-HIV drug combination for a patient. This study will determine whether using these tests to choose a drug combination and adding PIs to that combination will improve the patient's response to anti-HIV therapy.


Condition Intervention Phase
HIV Infections
Drug: lopinavir/ritonavir
Drug: indinavir sulfate
Drug: tenofovir disoproxil fumarate
Drug: ritonavir
Drug: fosamprenavir
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of the Predictive Value of Pharmacokinetic-Adjusted Phenotypic Susceptibility (C12h/IC50) on Antiretroviral Response to Ritonavir-Enhanced Protease Inhibitors in Subjects With Failure of Previous Protease Inhibitor-Based Regimens

Resource links provided by NLM:


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

Enrollment: 53
Study Completion Date: June 2005
Detailed Description:

Treatment options are limited for HIV infected individuals who have extensive treatment experience and harbor resistance to antiretrovirals (ARVs) from multiple drug classes. Increasing the concentration of PIs in a regimen may be one way to provide more substantial ARV activity. It is uncertain how combining specific PIs with RTV affects viral susceptibility and ARV effect. The relationship of PI concentration (e.g., Cmin) to virus susceptibility (IC50) may be a better predictor of treatment outcome than susceptibility alone. This study will evaluate the predictive value of pharmacokinetic-adjusted phenotypic susceptibility (C12h/IC50) on ARV response to ritonavir (RTV)-boosted regimens in patients failing their current PI-containing regimens.

Participants will have blood drawn during a screening visit for phenotypic assay and to determine viral load. At study entry, participants will discontinue their PIs while continuing to take their other ARVs. Each participant and his or her doctor will choose to add one of three RTV-boosted regimens: 1) indinavir (IDV) and RTV; 2) fosamprenavir (FPV) and RTV; or 3) lopinavir (LPV)/RTV plus additional RTV. Participants will take this regimen for 14 days. On Day 14, patients will have a 12-hour pharmacokinetic evaluation. On Day 15, patients will add tenofovir disoproxil fumarate (TDF) to their regimens and may choose to modify their other ARVs while continuing their RTV-boosted therapy. Participants will have additional study visits at Weeks 4, 8, 16, and 24. Study visits will include a physical exam and blood and urine tests. Participants will complete adherence questionnaires four times during the course of the study.

  Eligibility

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

Inclusion Criteria:

  • HIV infected
  • Viral load greater than 2500 copies/ml within 60 days of study entry
  • On regimen with at least one PI for a total of at least 48 weeks
  • On the same PI regimen for at least 90 days prior to study entry
  • Decreased susceptibility to two of these three PIs: LPV, APV, and IDV (documented by phenotype within 90 days prior to study entry)
  • Have taken a nonnucleoside reverse transcriptase inhibitor (NNRTI) for at least 12 weeks anytime in previous treatment history, or have decreased susceptibility to at least two NNRTIs
  • Have taken two or more nucleoside reverse transcriptase inhibitors (NRTIs) for at least 12 weeks anytime in previous treatment history
  • Agrees to use acceptable methods of contraception
  • Weighs 88 lbs or more

Exclusion Criteria:

  • Cannot tolerate RTV, APV, FPV, LPV/RTV, or IDV
  • Use of HIV vaccines, investigational agents, hydroxyurea, or therapy to affect the immune system within 60 days of study entry
  • Serious kidney problems
  • Pregnancy or breastfeeding
  • Alcohol or drug use that would interfere with the study
  • Serious illness that requires treatment or hospitalization (patients stable on therapy or who have finished therapy at least 14 days before study entry may be eligible)
  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: NCT00027339

Locations
United States, California
USC CRS
Los Angeles, California, United States
Stanford CRS
Palo Alto, California, United States, 94305-5107
UC Davis Medical Center
Sacramento, California, United States, 95814
Ucsd, Avrc Crs
San Diego, California, United States, 92103
United States, Colorado
University of Colorado Hospital CRS
Aurora, Colorado, United States, 80262
United States, Florida
Univ. of Miami AIDS CRS
Miami, Florida, United States
United States, Indiana
Methodist Hosp. of Indiana
Indianapolis, Indiana, United States, 46202
Indiana Univ. School of Medicine, Wishard Memorial
Indianapolis, Indiana, United States, 46202
United States, New York
NY Univ. HIV/AIDS CRS
New York, New York, United States, 10016
Beth Israel Med. Ctr., ACTU
New York, New York, United States, 10003
United States, North Carolina
Unc Aids Crs
Chapel Hill, North Carolina, United States, 275997215
Duke Univ. Med. Ctr. Adult CRS
Durham, North Carolina, United States, 27710
United States, Tennessee
Vanderbilt Therapeutics CRS
Nashville, Tennessee, United States, 37203
Puerto Rico
Puerto Rico-AIDS CRS
San Juan, Puerto Rico, 00936-5067
Sponsors and Collaborators
Investigators
Study Chair: Douglas Richman, MD University of California, San Diego
Study Chair: Joseph J. Eron, MD University of North Carolina, Chapel Hill
  More Information

Additional Information:
No publications provided

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00027339     History of Changes
Other Study ID Numbers: A5126, 10079, ACTG A5126, AACTG A5126
Study First Received: December 4, 2001
Last Updated: May 17, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
HIV-1
HIV Protease Inhibitors
RNA, Viral
Phenotype
Viral Load
Pharmacokinetics
Treatment Experienced

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

ClinicalTrials.gov processed this record on October 30, 2014