Is drug resistance unavoidable?
Current dogma dictates that all effective antiretroviral agents can and will select for drug-resistant virus. This view is driven by an understanding of the huge reservoir of replicating virus (1 1010 infected cells in an average patient), and its mutational propensity (about three mutations per virion per round of replication)28. Combining agents without cross-resistance promotes long-term efficacy. No treatment strategy has violated this paradigm, although some agents with measurable anti-HIV effects in patients, such as interferon- (IFN), have not yet been shown to promote drug-specific resistance29. In the case of IFN, this may simply reflect the nonselective or pleuripotent mechanism of action of the drug.One paradoxical drug development strategy involves promotion of mutagenesis during HIV replication, using ribonucleoside analogues, so that no progeny virus can survive30. In effect, the virus mutates itself out of existence. Whether HIV can develop resistance to such a mechanism
