Therapeutic drug monitoring in the management of HIV-infected patients.
The rate of HIV-positive patients that fails to reach or to maintain a durable virological suppression under anti-retroviral (ARV) therapy might be as high as 50%, therefore new tools to improve ARV drug efficacy are urgently needed. Among others, therapeutic drug monitoring (TDM) is a strategy by which the dosing regimen for a patient is guided by measurement of plasma drug levels, enabling physicians to optimize ARV drug efficacy and to avoid drug-related toxicity. The most used analytical methods to determine plasma levels of ARV drugs are HPLC-UV and HPLC-MS(/MS), recently MALDI-based methods and enzyme immunoassay (EIA) technologies have been also employed. The wide inter-patient variability in ARV drug pharmacokinetic supports the application of TDM to the clinical management of HIV-infected patients. Drug-drug and drug-food interactions, drug binding to plasma proteins, drug sequestering by erythrocytes, hepatic impairment, sex, age, pregnancy, and host genetic factors are sources of inter-patient variability affecting ARV drug pharmacokinetics. Combining the information of TDM and resistance tests in genotypic inhibitory quotient (GIQ) is likely to be of great clinical utility. Indeed, only two clinical trials on GIQ, both conducted using ARV drugs not more commonly in use, have shown clinical benefits. The design of new trials with long follow-up and sample size representative of the current HIV prevalence is urgently needed to give indications for GIQ as an early predictor of virological response. Here, the basic principles and the available methods for TDM in the management of HIV-infected patients are reviewed.
Ivanovic
Jelena
J
Istituto Nazionale per le Malattie Infettive IRCCS Lazzaro Spallanzani, Via Portuense 292, I-00149 Roma, Italy.
Jelena
Ivanovic
I
Nicastri
Emanuele
E
Emanuele
Nicastri
N
Ascenzi
Paolo
P
Paolo
Ascenzi
A
Bellagamba
Rita
R
Rita
Bellagamba
B
De Marinis
Elisabetta
E
Elisabetta
De Marinis
de M
Notari
Stefania
S
Stefania
Notari
N
Pucillo
Leopoldo Paolo
LP
Paolo
Pucillo Leopoldo
PL
Tozzi
Valerio
V
Valerio
Tozzi
T
Ippolito
Giuseppe
G
Giuseppe
Ippolito
I
Narciso
Pasquale
P
Pasquale
Narciso
N
D019380:Anti-HIV Agents / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002851:Chromatography, High Pressure Liquid; D002986:Clinical Trials as Topic; D004347:Drug Interactions; D016903:Drug Monitoring; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D007124:Immunoenzyme Techniques; D013058:Mass Spectrometry; D012680:Sensitivity and Specificity; D013056:Spectrophotometry, Ultraviolet
D019380:Anti-HIV Agents