ANTIRETROVIRAL THERAPY

Zidovudine and the other nucleoside analogues that inhibit the reverse transcriptase of HIV are the only approved antiretroviral agents. Although the benefits of these drugs are of limited duration, the use of these agents in combination, or sequentially, optimizes efficacy. Non-nucleoside reverse transcriptase inhibitors are well tolerated, synergistic with nucleosides, and are being tested in large clinical trials. Compounds that inhibit HIV protease are also being evaluated; a significant theoretical advantage of these drugs is their activity in chronically infected cells. With non-nucleoside reverse transcriptase inhibitors and protease inhibitors, resistant viruses may be rapidly selected resulting in a loss of antiviral activity; zidovudine resistance emerges more slowly, but is predictive of disease progression. Resistance thus remains an obstacle to achieving prolonged viral suppression. Quantitative assays of plasma HIV RNA are transforming the assessment and development of antiretroviral drugs and may develop into an integral part of patient management. Antiretroviral therapy for HIV-infected patients is rapidly evolving. In the near future, combination therapy, including agents active against different steps of the viral replication cycle, will become standard.