Alternative Dosing Strategy for Anti-HIV Drugs

HIV Infections Clinical Trial

Official title:

Concentration-Controlled Antiretroviral Therapy in Persons Experiencing Persistent Viremia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00059384
• Other study ID #: 2R01AI033835-08A1
• Secondary ID: 5M01RR000400-340
• Status: Completed
• Phase: Phase 4
• First received: April 23, 2003
• Last updated: September 16, 2008
• Start date: January 2003
• Est. completion date: December 2007

Study information

• Verified date: July 2007
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 66
• Est. completion date: December 2007
• Est. primary completion date: December 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infections

Intervention

Behavioral:
• Concentration-controlled therapy

Locations

Country	Name	City	State
United States	University of Colorado Health Sciences Center	Denver	Colorado

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Ability of the concentration-controlled strategies to achieve and maintain target concentrations
Primary	safety and tolerability of pharmacologic intensification
Primary	ability of pharmacologic intensification to achieve and maintain a sustained suppression in plasma HIV RNA
Secondary	Cross clade neutralizing antibody
Secondary	cellular immunity