Alternative Dosing Strategy for Anti-HIV Drugs - 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:	NCT00059384

Purpose

Anti-HIV drugs are usually given to patients at fixed, standardized doses. This study will investigate alternative ways of dosing anti-HIV drugs to improve viral control.

Study hypothesis: The optimal dosage regimen required to obtain the maximum benefit from antiretroviral therapy is achieved with strategies that control for pharmacokinetic and pharmacodynamic variability among patients.

Condition	Intervention	Phase
HIV Infections	Behavioral: Concentration-controlled therapy	Phase IV

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	Concentration-Controlled Antiretroviral Therapy in Persons Experiencing Persistent Viremia

Resource links provided by NLM:

MedlinePlus related topics: AIDS AIDS Medicines

U.S. FDA Resources

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

Primary Outcome Measures:

Ability of the concentration-controlled strategies to achieve and maintain target concentrations
safety and tolerability of pharmacologic intensification
ability of pharmacologic intensification to achieve and maintain a sustained suppression in plasma HIV RNA

Secondary Outcome Measures:

Cross clade neutralizing antibody
cellular immunity

Estimated Enrollment:	66
Study Start Date:	January 2003
Study Completion Date:	December 2007
Primary Completion Date:	December 2007 (Final data collection date for primary outcome measure)

Detailed Description:

While optimism for the benefits of antiretroviral therapy remain justified, the response to therapy varies widely. This variability arises because of differences among patients in virologic, immunologic, behavioral, and pharmacologic factors, all of which impact therapeutic success.

Antiretroviral agents are presently administered to adults in standard fixed doses. However, the same dose does not produce the same systemic and intracellular concentrations in all patients. Recent research has shown that adjusting the doses of antiretroviral agents to achieve target concentrations in plasma is associated with an improved anti-HIV response compared with standard dose therapy. This study will extend the paradigm of concentration-controlled therapy to develop intensified pharmacologic regimens for patients experiencing persistent viremia while receiving antiretroviral therapy.

Two approaches will be investigated: 1) a regimen that targets concentrations of each antiretroviral drug between the 50th and 75th percentile of expected concentrations in adults; and 2) a novel regimen in which the target concentrations are based upon a desired ratio between phenotypic drug susceptibility (IC90) and the concentrations of pharmacologically active moieties, specifically intracellular nucleoside triphosphates and unbound protease and nonnucleoside inhibitors.

Participants will be randomized to either one of the investigational approaches (Cohort II) or to a control group receiving standard dose therapy (Cohort I). There are two study visits in the first month; after the first month, study visits are scheduled monthly for five additional months. Study visits include laboratory tests of virologic and immunologic parameters, pharmacokinetic sampling, and adherence counseling and monitoring.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria for Cohort I:

HIV infected
Receiving therapy with 3 or more antiretroviral medications and and willing to continue this regimen
Achieved a greater than 1 log10 reduction in plasma HIV-RNA from baseline within 8 weeks after the start of current therapy
Current plasma HIV-RNA levels greater than 500 copies/mL and less than 10,000 copies/mL

Inclusion Criteria for Cohort Cohort II:

HIV infected
Receiving antiretroviral therapy and have been determined to have had virologic failure
Will or have been changed to a new antiretroviral regimen (addition of greater than one new antiretroviral agent), but have not received this new regimen for more than 4 weeks as of study entry
HIV RNA of 2500 copies/mL or greater at screening

Exclusion Criteria:

Concurrent investigational antiretroviral agent
Malignancy, including Kaposi's sarcoma, requiring systemic chemotherapy
Active opportunistic infection requiring therapy within 14 days prior to study entry
Drug-resistant mutations that necessitate a change in antiretroviral regimen
Active drug or alcohol use or dependence
Certain laboratory abnormalities
Pregnant or breastfeeding
Known nonadherence with medications and scheduled clinic visits
Any medical condition that, in the opinion of the investigators, would preclude successful completion of the study

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00059384

Locations

United States, Colorado
University of Colorado Health Sciences Center
Denver, Colorado, United States, 80262

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

Principal Investigator:

Courtney V. Fletcher, PharmD

University of Colorado at Denver and Health Sciences Center

More Information

No publications provided

Study ID Numbers:	2R01AI33835-08A1, 5M01RR000400-340420, 3M01RR000400-34S1A20420ú
Study First Received:	April 23, 2003
Last Updated:	September 16, 2008
ClinicalTrials.gov Identifier:	NCT00059384 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

Treatment experienced
Therapeutic Drug Monitoring

Additional relevant MeSH terms:

Virus Diseases
Sexually Transmitted Diseases, Viral
RNA Virus Infections
Slow Virus Diseases
Immune System Diseases
HIV Infections

Sexually Transmitted Diseases
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Infection
Retroviridae Infections
Immunologic Deficiency Syndromes

ClinicalTrials.gov processed this record on November 27, 2009