Alternative Dosing Strategy for Anti-HIV Drugs

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

Study Description

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 Design

• 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

Arms and Interventions

Outcome Measures

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

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, Denver

More Information

• ClinicalTrials.gov Identifier: NCT00059384
• Other Study ID Numbers: 2R01AI033835-08A1 ( U.S. NIH Grant/Contract ); 5M01RR000400-340420; 3M01RR000400-34S1A20420ú
• First Posted: April 24, 2003
• 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; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Immunologic Deficiency Syndromes; Immune System Diseases