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

Sponsor:	National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00027339

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 II

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:

Genetics Home Reference related topics: complement factor I deficiency

MedlinePlus related topics: HIV/AIDS HIV/AIDS Medicines

Drug Information available for: Tenofovir Indinavir Ritonavir Indinavir Sulfate Lopinavir Tenofovir disoproxil Tenofovir Disoproxil Fumarate Fosamprenavir Fosamprenavir sodium Fosamprenavir calcium

U.S. FDA Resources

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

Estimated Enrollment:	108
Study Completion Date:	May 2007

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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00027339

Show 32 Study Locations

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

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:

Click here for more information about indinavir sulfate This link exits the ClinicalTrials.gov site

Click here for more information about ritonavir This link exits the ClinicalTrials.gov site

Click here for more information about tenofovir disoproxil fumarate This link exits the ClinicalTrials.gov site

Click here for more information about lopinavir/ritonavir This link exits the ClinicalTrials.gov site

Click here for more information about fosamprenavir This link exits the ClinicalTrials.gov site

Haga clic aquí para ver información sobre este ensayo clínico en español. This link exits the ClinicalTrials.gov site

No publications provided

ClinicalTrials.gov Identifier:	NCT00027339 History of Changes
Other Study ID Numbers:	ACTG A5126, AACTG A5126, DAIDS-ES ID 10079
Study First Received:	December 4, 2001
Last Updated:	August 6, 2009
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:

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
Protease Inhibitors
Indinavir
Ritonavir
Lopinavir

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

ClinicalTrials.gov processed this record on February 12, 2012