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.

Condition	Treatment or Intervention	Phase
HIV Infections	Behavior: Concentration-controlled therapy	Phase IV

Further Study Details: 

Expected Total Enrollment:  66

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.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

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

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

Study chairs or principal investigators

Courtney V. Fletcher, PharmD,  Principal Investigator,  University of Colorado   

Study ID Numbers:  2R01AI33835-08A1; 5M01RR000400-340420; 3M01RR000400-34S1A20420ú
Record last reviewed:  November 2004
Last Updated:  November 16, 2004
Record first received:  April 23, 2003
ClinicalTrials.gov Identifier:  NCT00059384
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08