[Treatment of HIV infection with nucleoside analogs: present status]

Nucleotide analogues inhibit the reverse transcriptase of both human immunodeficiency virus (HIV)-1 and -2. Molecules currently available for clinical use in infected patients include zidovudine (AZT), didanozine (ddI) and zalcitabine (ddC). 2',3'-didehydro-3'dideoxythymidine (D4T, stavudine) and 3TC (GR 109714X) are in earlier stages of development. Currently, first intention antiretroviral treatment relies on AZT while ddI is used as a back-up drug in intolerant or unresponsive patients. Combinations of nucleotide drugs (AZT+ddI or AZT+ddC) would appear to be useful in light of modifications in substitution markers and the promising clinical results currently under assessment in phase III trials. The nucleotide analogues currently used in single drug protocols lead to resistance by mutation of the reverse transcriptase gene. This acquired resistance may regress at treatment withdrawal although the clinical significance is not clearly understood. The development of other classes of antiviral drugs (antiproteases, non-nucleosidic inhibitors of reverse transcriptase) should open new prospects for the use in combination with nucleotide analogues.