The era of
antiviral therapy directed against HIV-1 has now entered its second decade. In the twelve years since the FDA approved the first antiretroviral
drug zidovudine there have been a number of seminal developments that have revolutionized the approach to
therapy. These advances converged to change the treatment paradigm from one of therapeutic nihilism to that of cautious optimism. First, several trials demonstrated that combination
therapy of
nucleoside reverse transcriptase inhibitors (NRTIs) is superior to monotherapy in extending survival and delaying
disease progression. Second, the concept of virologic latency in asymptomatic HIV-infected patients was revised. 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 measure the circulating HIV plasma
RNA. HIV viral load has been shown to be a sensitive predictor of
disease progression and a valuable marker of response to
therapy. However, none of these developments would have translated into improved patient care without the advent of two new classes of drugs-the
protease inhibitors (PIs) and the nonnucleoside
reverse transcriptase inhibitors (NNRTIs).