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189
What Antiretroviral Therapy To Switch To?
P Yeni
Hosp Bichat, Paris, France
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Background: Similarly to initial therapy, effective rescue therapy requires the combination of active drugs, optimal drug exposure, and favorable safety profile. These conditions must be fulfilled to reach the objective of attaining and maintaining an undetectable viral load in the plasma. Drug resistance has been reported in up to 87% of patients (pts) taking antiretroviral therapy, and recent data demonstrate that intra-class cross-resistance is more frequent than anticipated, limiting the number of active drugs available for rescue therapy. In addition, resistance is a long-lasting phenomenon that may become undetectable in the plasma following a change in therapy, and re-emerge with the next regimen, being responsible for the failure of simplification therapy for example. Because drug-resistance and cross-resistance are so frequent and often unpredictable from treatment history, resistance testing is an important step in the selection of the next regimen, which should include 3 or more active drugs. A number of confounding factors have been identified and explain why the clinical benefit of resistance testing has not been demonstrated in all prospective randomized studies. In addition, tests have become more accurate, due to progresses in the definition of resistance, as well as technical improvements. Drug exposure is the second important concept: A high level of variability has been demonstrated for many drugs, impacting the antiviral activity of the regimen. However, the benefit of ARV dose adaptation was not demonstrated in prospective randomized studies performed in treatment-experienced pts, making difficult to recommend therapeutic drug monitoring in all pts starting rescue therapy. Because results from tests for drug-resistance and drug-exposure do not translate unequivocally into the best selection of drugs for rescue therapy, clinical implications resulting from both concepts are important to discuss. These implications encompass drug recycling, treatment intensification, boosted protease inhibitors, protease inhibitor combinations, and other strategies.
Conclusion: Although cross-resistance will extend to new drugs currently in clinical development, some molecules pertaining to already existing or new classes of drugs, show promise in the setting of rescue therapy and will be discussed.
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