|
Project Topic
|
The massive global increase in the number of HIV infected patients on antiretroviral therapy (ART) over the last few years has resulted to improved quality of life and reduced death rate. The UN aims to achieve 90% viral load suppression levels among ART exposed patients by the year 2020 [1]. This requires that factors that affect VL suppression be identified and addressed. One such factor is the level of anti-retrovirals (ARVs) within the biological system, assessable by therapeutic drug monitoring (TDM). ART levels within a biological system may be affected by dosing regimens, associated toxicities, drug-drug, drug-food interactions, individual variations to pharmacokinetics and systemic bioavailability resulting in ART levels being sub-therapeutic, therapeutic or supra therapeutic [2]. TDM allows for actual drug exposure to be determined, patient compliance gleaned, providing opportunity for dose adjustment, increasing ART efficacy among some populations while avoiding drug related toxicity [3, 4]. TDM can be used as a tool to measure adherence in addition to traditionally used methods. The use of hair to assess pharmacokinetic availability of drugs in the system was considered advantageous over plasma as it looked at the systematic levels of drug over a period of weeks as against plasma, which provides a snapshot [5] and might be more acceptable being less invasive. TDM could trigger early interventions to address non-adherence or correct low pharmacokinetic levels. The current treatment guideline in Nigeria does not include monitoring of ARV level [6] although some reports have suggested better treatment outcomes amongst patients whose treatment is guided by TDM [7, 8]. Developing TDM requires that the science behind the extraction of ARVs from plasma, peripheral blood mononuclear cells (PBMCs), and hair be understood. Furthermore, the science behind small molecule separation such as choice of mobile phase and chromatographic matrix needs to be understood and optimized for the particular application. Instrumentation in the use of High Performance Liquid Chromatography and Mass spectrometry, required for detection and quantification of ARV, and associated data processing and interpretation tools, will also be required. The selected training fellowship will allow me become proficient in skills in drug profile safety, tolerability, pharmacokinetics and harmacodynamics for novel compounds. These skills are useful for engaging in clinical trials phase I and II, one of our institutional goals but can in addition be applied to estimating ARV levels in HIV patients to understand the contribution of ARV bioavailability and dosing to failue.
|
