Therapeutic drug monitoring of antiretrovirals in human immunodeficiency virus infection

The era of antiviral therapy directed against HIV-1 has now entered its sec ond decade. In the twelve years since the FDA approved the first antiretrov iral drug zidovudine there have been a number of seminal developments that have revolutionized the approach to therapy. These advances converged to ch ange the treatment paradigm from one of therapeutic nihilism to that of cau tious optimism. First, several trials demonstrated that combination therapy of nucleoside reverse transcriptase inhibitors (NRTIs) is superior to mono therapy in extending survival and delaying disease progression. Second, the concept of virologic latency in asymptomatic HIV-infected patients was rev ised. Mathematic modelling demonstrated that there is an ongoing high level of virus production driving a rapid turnover of CD4 cells at all stages of infection, Hence it was concluded that the aim of antiretroviral therapy ( ART) should be to "hit early and hit hard." Third, significant advances in molecular virology facilitated the development of quantitative methods to m easure the circulating HIV plasma RNA. HIV viral load has been shown to be a sensitive predictor of disease progression and a valuable marker of respo nse to therapy. However, none of these developments would have translated i nto improved patient care without the advent of two new classes of drugs-th e protease inhibitors (PIs) and the nonnucleoside reverse transcriptase inh ibitors (NNRTIs).