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The correct choice of a potent first\u2010line therapy to achieve sustained long\u2010term suppression of viral replication provides the best chance of preventing treatment failure and drug resistance. Clinical studies have demonstrated that drugs with a high barrier to resistance have significantly lower rates of resistance compared with those with a low barrier to resistance. Management of treatment failure requires precise clinical and virological monitoring as well as early treatment intervention with appropriate noncross\u2010resistant antivirals. Long\u2010term surveillance of treatment efficacy and possible emergence of drug resistance is necessary in patients who have been sequentially treated with multiple antivirals. 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