Alternative Dosing Strategy for Anti-HIV Drugs

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: NCT00059384
Recruitment Status : Completed
First Posted : April 24, 2003
Last Update Posted : September 17, 2008
Information provided by:
National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary:

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 or disease Intervention/treatment Phase
HIV Infections Behavioral: Concentration-controlled therapy Phase 4

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.

Study Type : Interventional  (Clinical Trial)
Enrollment : 66 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Concentration-Controlled Antiretroviral Therapy in Persons Experiencing Persistent Viremia
Study Start Date : January 2003
Actual Primary Completion Date : December 2007
Actual Study Completion Date : December 2007

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Primary Outcome Measures :
  1. Ability of the concentration-controlled strategies to achieve and maintain target concentrations
  2. safety and tolerability of pharmacologic intensification
  3. ability of pharmacologic intensification to achieve and maintain a sustained suppression in plasma HIV RNA

Secondary Outcome Measures :
  1. Cross clade neutralizing antibody
  2. cellular immunity

Information from the National Library of Medicine

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, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

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): NCT00059384

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)
Principal Investigator: Courtney V. Fletcher, PharmD University of Colorado, Denver Identifier: NCT00059384     History of Changes
Other Study ID Numbers: 2R01AI033835-08A1 ( U.S. NIH Grant/Contract )
3M01RR000400-34S1 ( U.S. NIH Grant/Contract )
First Posted: April 24, 2003    Key Record Dates
Last Update Posted: September 17, 2008
Last Verified: July 2007

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Treatment experienced
Therapeutic Drug Monitoring

Additional relevant MeSH terms:
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases