How to win the HIV-1 drug resistance hurdle race: running faster or jumping higher?

摘要: Infections by the human immunodeficiency virus type 1 (HIV-1), causative agent of acquired syndrome (AIDS), are still totaling an appalling 36.7 millions worldwide, with 1.1 million AIDS deaths/year and a similar number yearly new infections. All this, in spite discovery HIV-1 as etiological more than 30 years ago introduction effective combinatorial antiretroviral therapy (cART), able to control disease progression, 20 ago. Although very effective, current cART is plagued emergence drug-resistant viral variants most efforts development novel direct-acting antiviral agents (DAAs) against have been devoted toward fighting resistance. In this review, rather providing detailed listing all drugs corresponding resistance mutations, we aim, through relevant examples, at presenting general reader conceptual shift approaches that being taken overcome hurdle. From classic ‘running faster’ strategy, based on DAAs active mutant viruses selected previous and/or high genetic barrier resilience, ‘jumping higher’ approach, which looks cell, virus, source valuable drug targets, order make cellular environment non-permissive replication both wild-type mutated viruses.