ANTIRETROVIRAL THERAPY

Zidovudine and the other nucleoside analogues that inhibit the reverse transcriptase of HIV are the only approved antiretroviral agents. Alt hough 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, synerg istic with nucleosides, and are being tested in large clinical trials. Compounds that inhibit HIV protease are also being evaluated; a signi ficant theoretical advantage of these drugs is their activity in chron ically infected cells. With non-nucleoside reverse transcriptase inhib itors and protease inhibitors, resistant viruses may be rapidly select ed resulting in a loss of antiviral activity; zidovudine resistance em erges more slowly, but is predictive of disease progression. Resistanc e thus remains an obstacle to achieving prolonged viral suppression. Q uantitative assays of plasma HIV RNA are transforming the assessment a nd development of antiretroviral drugs and may develop into an integra l 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 replicat ion cycle, will become standard.