Strategies for the optimal sequencing of antiretroviral drugs toward overcoming and preventing drug resistance

Abstract

Drug regimens now offer more potent, less toxic and more durable choices in the treatment of HIV disease than ever before. This has led to a need to consider the convenient, sequential use of active antiretroviral combinations. Ritonavir-boosted protease inhibitors (PIs) can now be potentially sequenced in a manner that uses the least cross-resistance-prone PI at the start of therapy while leaving the most cross-resistance-prone drug for later, if the latter retains activity against commonly observed drug-resistant forms. Similarly, such new drugs as tenofovir, abacavir and emtricitabine, which make up current nucleoside backbone options, can be potentially sequenced, since each of them selects for an individual pattern of resistance mutations that are generally distinct from those selected by previously popular thymidine analogs such as zidovudine and stavudine.