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. Primary Objectives (Therapeutic Drug Monitoring [TDM]) 1. To define the population of patients for whom pharmacologic intervention would be appropriate (based on expert panel recommendation) and to define factors predictive of the need for TDM intervention. 2. To develop and validate algorithms and clinically relevant cut-points for interpretation of pharmacological parameters as determined by achievement of desired pharmacological measures after the TDM adjustment. Secondary Objectives (Therapeutic Drug Monitoring [TDM]) 1. To define the proportion of patients who have PK interventions recommended and whose primary provider implements the recommendation and to describe why recommendations are not followed. 2. To define the proportion of patients in whom a TDM change is implemented who achieve the desired pharmacological effect as assessed by repeated plasma concentrations. 3. To explore the Cmin/IC50 ratio as a predictor of virologic success and as a metric used to monitor and change drug regimens. 4. To determine the independent value (from the adherence intervention) of therapeutic drug monitoring (TDM) in improving HIV RNA reduction for patients initiating or changing ARV therapy. 5. To determine the correlation between plasma ARV concentrations and adverse events (including fasting lipid concentrations) and to see if TDM can be used to minimize toxicity of antiretroviral therapy. 6. To see if PI and NNRTI concentrations (as assessed by repeated trough levels) are maintained above threshold levels with the adherence interventions. 7. To determine the correlation between adherence, as assessed by MEMS cap devices, and PI and NNRTI trough concentrations. 8. To determine the effect of the TDM on CD4 change from baseline. 9. To explore additional pharmacodynamic markers, such as AUC, Cmax in combination with susceptibility values (IC50 or IC90) as predictors of virologic response. 10. To investigate the role of immunity in sustaining ART-induced virus suppression. Primary Objectives (Adherence) 1. To determine whether a brief (5 session), clinic-based training intervention that includes a practice trial of an inert medication regimen in addition to psychoeducational components is superior to an intervention with psychoeducational components alone, and to 'usual clinical care' in improving adherence to HAART. 2. To determine whether the training intervention is effective in maintaining improved medication adherence for a period of 12 months. 3. To assess the effects of the training intervention, and adherence in general, on virologic measures of clinical outcome (e.g., Does improved adherence reduce viral load and increase CD4 count? What level of poor adherence is associated with development of viral resistance?). To further examine the relationship between adherence and clinical outcome, the investigators will use data to calibrate a structural model of this relationship to predict clinical outcome trajectory for patients before treatment begins. Secondary Objectives (Adherence) 1. To determine whether, in the context of a training intervention, adherence to the inert medication regimen predicts adherence to HAART. 2. To identify psychosocial, neuropsychological and contextual factors, as well as attitudes and beliefs about antiretroviral therapy, that impede or facilitate adherence.
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