Alternative Dosing Strategy for Anti-HIV Drugs

Phase 4

Completed

• Conditions: HIV Infections

• Registration Number: NCT00059384
• Lead Sponsor: 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.

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 Timeline

• Study Start: 2003-01
• Study First Submitted: 2003-04-23
• Study First Submitted QC: 2003-04-23
• Study First Posted: 2003-04-24
• Status Verified: 2007-07
• Primary Completion: 2007-12
• Study Completion: 2007-12
• Last Update Submitted: 2008-09-16
• Last Update Posted: 2008-09-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 66

Inclusion Criteria

Not provided

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

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Cross clade neutralizing antibody
cellular immunity

Trial Locations

Locations (1)

University of Colorado Health Sciences Center; 🇺🇸 Denver, Colorado, United States