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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00027339
Recruitment Status : Completed
First Posted : December 5, 2001
Last Update Posted : May 21, 2012
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary:
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 or disease Intervention/treatment Phase
HIV Infections Drug: lopinavir/ritonavir Drug: indinavir sulfate Drug: tenofovir disoproxil fumarate Drug: ritonavir Drug: fosamprenavir Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 53 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (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
Actual Study Completion Date : June 2005

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Information from the National Library of Medicine

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Ages Eligible for Study:   13 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00027339

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United States, California
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
Indiana Univ. School of Medicine, Wishard Memorial
Indianapolis, Indiana, United States, 46202
Methodist Hosp. of Indiana
Indianapolis, Indiana, United States, 46202
United States, New York
Beth Israel Med. Ctr., ACTU
New York, New York, United States, 10003
New York, New York, United States, 10016
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
National Institute of Allergy and Infectious Diseases (NIAID)
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Study Chair: Douglas Richman, MD University of California, San Diego
Study Chair: Joseph J. Eron, MD University of North Carolina, Chapel Hill
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Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID) Identifier: NCT00027339    
Other Study ID Numbers: A5126
10079 ( Registry Identifier: DAIDS ES )
ACTG A5126
First Posted: December 5, 2001    Key Record Dates
Last Update Posted: May 21, 2012
Last Verified: May 2012
Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
HIV Protease Inhibitors
RNA, Viral
Viral Load
Treatment Experienced
Additional relevant MeSH terms:
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HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors