Clinical pharmacology of antiretroviral therapy.
Antiretroviral therapy represents by all means a new branch of anti-infective chemotherapy, and in order to describe the mode of action of antiretrovirals, a series of inferences from anti-bacterial chemotherapy were made. The currently available antiretroviral agents can be classified as time-dependent drugs, and therefore the key pharmacokinetic parameter adopted in their clinical-pharmacological assessment is the concentration at the end of the dosing interval (Ctrough). By focusing on this parameter, the application of Therapeutic Drug Monitoring (TDM) allows for the successful individual tailoring of the drug dosage in some clinical circumstances, such as treatment of drug-resistant infections, drug-drug interactions and side effects. While this procedure has now been sufficiently standardized for protease inhibitors (PIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs), no clinical applications are yet recognized for nucleoside/nucleotide reverse transcriptase inhibitors (N/NtRTIs) and fusion inhibitors. The main unfavourable peculiarity of HIV infection, such as the need for lifelong treatment, is one of the reasons why increasing attention is being paid to pharmacological aspects of antiretroviral therapy. Issues like treatment potency, maintenance over time of the immunovirological benefit and long-term side effects require intensive pharmacological investigation in order to obtain the information on which basing the most convenient strategy to be adopted for the therapeutical management of this condition.
Di Perri
G
G
Department of Clinical Infectious Diseases, University of Torino.
Sinicco
A
A
Audagnotto
S
S
Gobbi
F
F
Canta
F
F
Marrone
R
R
Bonora
S
S
D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000032:analysis / Q000494:pharmacology* / Q000627:therapeutic use*; D016903:Drug Monitoring / Q000379:methods*; D006678:HIV / Q000187:drug effects*; D023581:HIV Fusion Inhibitors / Q000008:administration & dosage / Q000032:analysis / Q000494:pharmacology / Q000627:therapeutic use; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000032:analysis / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D018894:Reverse Transcriptase Inhibitors / Q000032:analysis / Q000494:pharmacology / Q000627:therapeutic use
D019380:Anti-HIV Agents; D023581:HIV Fusion Inhibitors; D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors