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Is Drug Resistance in First-Line Therapy against All Antiretroviral Agents Inevitable?

Mark A Wainberg, Thibault Mespl?de

Drug resistance has been observed in regard to all anti-retroviral drugs that have been studied until now. The most recent drug to be approved for use in HIV therapy is dolutegravir, an HIV integrase inhibitor, that was approved for therapy by the Food and Drug Administration in the United States in 2013. Dolutegravir is the only HIV drug that has not selected for resistance mutations in the clinic when used as part of first-line therapy. We have hypothesized that this is due to the long binding time of dolutegravir to the integrase enzyme as well as greatly diminished replication capacity on the part of viruses that might become resistant to dolutegravir and that are unable to successfully replicate in infected individuals.