Advances in HIV pharmacology: protein binding, pharmacogenomics, and therapeutic drug monitoring.

Developing better antiretroviral drugs, individualizing therapy through patient genetic profiling, and maintaining effective drug concentrations with therapeutic drug monitoring (TDM) represent 3 current areas of interest in the field of HIV pharmacology. This article first examines antiretroviral drug binding to plasma proteins, a factor that affects the amount of free drug available to enter cells. Protein binding influences drug development, raising questions about whether the drug levels required for appropriate therapeutic effect can be achieved at tolerable doses. Second, individualized antiretroviral therapy has generated considerable interest, but much work remains in the area of pharmacogenomics before this strategy finds a place in clinical practice. Finally, studies are mixed on the benefits of TDM; although such monitoring may be appropriate in some settings, such as pregnancy and pediatrics, data are currently lacking to support its routine use in HIV care. Although data on these pharmacologic strategies do not currently support their widespread clinical application, ongoing research of such strategies offers hope for future improvement of the efficacy of antiretroviral therapy. This article summarizes a presentation given by Charles W. Flexner, MD, at the November 2002 International AIDS Society-USA course in San Diego.