Therapeutic drug monitoring and the inhibitory quotient of antiretroviral drugs: can they be applied to the current situation?
Therapeutic drug monitoring is attracting growing interest as a means of increasing the effectiveness of antiretroviral therapy and of decreasing its toxicity, although data supporting this strategy are still scarce. Currently, nucleoside analog reverse-transcriptase inhibitors (NARTI) are not candidates because their effect depends on their active intracellular form and not on plasma concentration. Protease inhibitors (PI) and non-nucleoside analogue reverse-transcriptase inhibitors (NNARTI) meet the criteria for therapeutic drug monitoring. The main limitations are that the parameters to be monitored in order to measure exposure to the drug and the effective concentration of the drug have not been well defined. The few studies performed in treatment-naive patients have demonstrated that monitoring improves therapeutic efficacy. This strategy will be particularly useful when the risk of subtherapeutic or toxic concentrations is especially high (pharmacokinetic interactions, intestinal malabsorption, adverse effects, virological failure without obvious cause, pregnancy, children). Although it remains to be standardized, the inhibitory quotient integrates pharmacological and virological parameters and is useful in patients with prior virological failure. Any therapeutic drug monitoring program should be accompanied by measures to monitor and improve treatment adherence. There are good reasons to believe that therapeutic drug monitoring can be useful to improve treatment in specific circumstances. However, before its widespread use as a routine method can be recommended, the parameters to be used should be standardized and studies with appropriate methodology should be performed to define the role of therapeutic drug monitoring in distinct clinical situations.
Ribera
Esteve
E
Servicio de Enfermedades Infecciosas, Hospital Universitari Vall d'Hebron, Barcelona, Spain. eribera@vhebron.net
López-Cortés
Luis Fernando
LF
Soriano
Vicente
V
Casado
José Luis
JL
Mallolas
Josep
J
D000465:Algorithms; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D019540:Area Under Curve; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring / Q000379:methods / Q000706:statistics & numerical data; D014644:Genetic Variation; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D054303:HIV Reverse Transcriptase / Q000009:adverse effects / Q000037:antagonists & inhibitors; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D015337:Multicenter Studies as Topic / Q000706:statistics & numerical data; D010349:Patient Compliance; D011355:Prodrugs / Q000493:pharmacokinetics; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D011355:Prodrugs; D018894:Reverse Transcriptase Inhibitors; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase