Practical Guidelines to Interpret Plasma Concentrations of Antiretroviral Drugs

Abstract

Several relationships have been reported between antiretroviral drug concentrations and the efficacy of treatment, and toxicity. Therefore, therapeutic drug monitoring (TDM) may be a valuable tool in improving the treatment of HIV-1-infected patients in daily practice. In this regard, several measures of exposure have been studied, e.g. trough and maximum concentrations, concentration ratios and the inhibitory quotient. However, it has not been unambiguously established which pharmacokinetic parameter should be monitored to maintain optimal viral suppression. Each pharmacokinetic parameter has its pros and cons. Many factors can affect the pharmacokinetics of antiretroviral agents, resulting in variability in plasma concentrations between and within patients. Therefore, plasma concentrations should be considered on several occasions. In addition, the interpretation of the drug concentration of a patient should be performed on an individual basis, taking into account the clinical condition of the patient. Important factors herewith are viral load, immunology, occurrence of adverse events, resistance pattern and comedication. In spite of the described constraints, the aim of this review is to provide a practical guide for TDM of antiretroviral agents. This article outlines pharmacokinetic target values for the HIV protease inhibitors amprenavir, atazanavir, indinavir, lopinavir, nelfinavir, ritonavir and saquinavir, and the non-nucleoside reverse transcriptase inhibitors efavirenz and nevirapine. Detailed advice is provided on how to interpret the results of TDM of these drugs.

No Need for Lopinavir Dose Adjustment during Pregnancy: a Population Pharmacokinetic and Exposure-Response Analysis in Pregnant and Nonpregnant HIV-Infected Subjects

“…This plasma LPV trough target is approximately 15 times the protein binding-adjusted plasma concentration required to obtain 50% of the maximum effect in vivo (EC 50 ) for the wild-type HIV-1 (43)(44)(45)(46).…”

Reversed-phase liquid chromatographic method with spectrophotometric detection for the determination of antiretroviral drugs

“…Plasma samples were obtained from blood through centrifugation at 3500 × g for 15 min. Plasma samples were spiked with different amounts of AIDS drugs covering the typical concentration ranges described in clinical studies [5].…”

“…Besides, the efficacy of new doses and new HAART combinations, and pharmacokinetic studies of drug interactions can also be investigated by TDM. TDM of antiretroviral drugs has been primarily focused on NNRTI and PI [5]. The significance of TDM in the case of NRTIs has been more limited although new trends are interested in the study of intracellular levels of NRTI drugs and triphosphate metabolites [6].…”

“…In general, high-performance liquid chromatography (HPLC) with UV detection is successful for achieving the required sensitivity and selectivity in most of the applications. Detection limits of HPLC-UV methods cited above are sufficient for monitoring the drug concentrations in plasma of patients which typically ranges from 0.1 to 10 g mL −1 [2,5]. If necessary, detection limits and selectivity can be improved using HPLC coupled to mass spectrometry (MS).…”

“…Another aspect to be improved is the analysis time which typically ranges between 20 and 50 min for most of the methods reported. As a conclusion, faster and simpler analytical methods are welcome to satisfy the increasing demand of TDM of antiretroviral drugs [2][3][4][5].…”