Reasons for TDM in AIDS

TDM permits timely dosage adjustments based on individual plasma concentrations to prevent prolonged exposure to toxic or subtherapeutic concentrations of drugs. Numerous studies have shown lack of adequate viral suppression in the absence of TDM (17-20). The PIs and NNRTIs show a concentration-effect relationship (15,16,21-25), although large inter- and intraindividual differences have been observed in many of the HIV drugs with regard to drug disposition, making prediction of a plasma concentration for any given dose exceedingly difficult (26-29). Finally, narrow therapeutic index is seen for the majority of the antiretroviral drugs, with toxicities ranging from nausea and vomiting, to pancreatitis, nephrolithiasis, and neurologic effects (8-10,12,23). The ATHENA study in the Netherlands (16) was a randomized, prospective clinical trial and evaluated the role of TDM in the management of HIV-1-infected patients. The outcomes in the TDM cohort were significantly better than those of the non-TDM group. This finding is all the more impressive, considering <20% of the physicians responded to the dosing recommendations of the intervention group (13). One of the main reasons for TDM of antiretrovirals is the well-known lack of compliance of patients on long-term therapy for chronic illnesses. For HIV/AIDS patients, this lack of adherence to their drug regimens commonly occurs in 33-60% of patients (1-3). When failure of antiretroviral therapy occurs, assessment of compliance (adherence) by TDM, prior to resistance testing is very important. Documentation of ongoing antiretroviral drug presence makes the results of both genotypic and pheno-typic HIV resistance tests more meaningful. Drug-drug interactions and interpatient variability in drug handling are other major reasons for TDM in this population.

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