A novel method for determining the inhibitory potential of anti-HIV drugs.
In the absence of cure, most HIV-1-infected individuals will require lifelong treatment. It is therefore essential to optimize highly active antiretroviral therapy. Recent research has shown that the slope parameter or Hill coefficient, which describes the steepness of a dose-response curve, is a critical missing dimension in the evaluation of the activity of antiviral drugs. Based on this finding, instantaneous inhibitory potential (IIP) has been derived as a new measure of antiviral drug activity. IIP incorporates the slope parameter and thus is a more accurate pharmacodynamic measure of antiviral activity than current measures such as IC(50) and inhibitory quotient. Determining how to use IIP to predict the in vivo efficacy of anti-HIV-1 drugs is nevertheless important. This article discusses recent advances in in vitro measures of antiviral activity and the therapeutic implications of the dose-response curve slope and IIP.
Shen
Lin
L
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Rabi
S Alireza
SA
Siliciano
Robert F
RF
D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D004305:Dose-Response Relationship, Drug; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology; D017320:HIV Protease Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D020128:Inhibitory Concentration 50; D014779:Virus Replication
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors