A5146 A HIV TRIAL EVALUATING THE IMPACT OF THERAPEUTIC DRUG MONITORING

点击翻译按钮获取中文摘要

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Hypothesis: 1. Increased doses of protease inhibitor (PI) drugs will be more effective in lowering viral load (amount of HIV in the blood) than continuing standard doses of PIs. The dose increases of the PI drugs will be based upon therapeutic drug monitoring (TDM) which involves measuring blood levels of PIs. 2. Using an NIQ (normalized inhibitory quotient) helps control HIV infection better than not using the NIQ and TDM drug levels. 3. This study will also examine the safety of increasing doses of PI drugs based on TDM. Experimental Design: A5146 is an open-label, randomized, multicenter trial evaluating the impact of therapeutic drug monitoring on virologic response to a salvage regimen in PI-experienced subjects who have a low normalized inhibitory quotient to at least one of the PIs in their salvage regimen. Subjects failing their second, third, or fourth combination antiretroviral regimen will have a screening resistance test performed using a virtual phenotype while they remain on their failing regimen. At entry, all subjects will enter Step 1, in which a salvage regimen will be selected by the subject's clinician using results of this resistance test. All subjects will have timed plasma samples obtained for PI trough levels on the new regimen at week 2, and will receive results of their NIQ (>1 or > 1) before week 4, in order to determine eligibility for randomization at entry into Step 2. Step 2 consists of 3 arms: standard of care (SOC) (Arm A), TDM + SOC (Arm B), and an observational arm (Arm C). Enrollment to the study will be closed once a total of 450 subjects have entered Step 2 (150 subjects with NIQ >1 each in Arms A and B, and 150 subjects with NIQ >1 in Arm C). Adherence Questionnaires: A baseline adherence questionnaire will be administered at entry into the study (Step 1). Subsequent adherence assessments will use the self-report adherence form. Information from these questionnaires is confidential and the questionnaires are completed by the subject. The questionnaires each require an additional 5-10 minutes of the subject's time.