Targeting HIV: antiretroviral therapy and development of drug resistance.
Inhibitors of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) and protease (PR) are widely used in the clinical treatment of AIDS. However, the emergence of drug-resistant variants of HIV-1 severely limits the long-term effectiveness of these drugs. In this review, the molecular basis of resistance to RT and PR inhibitors will be addressed, focusing on the mutations that confer resistance to nucleoside and non-nucleoside drugs. The emergence of multidrug-resistant viruses results from the introduction of potent antiretroviral therapy and involves the combined effects of different drug-resistance mutations. The optimization of current antiretroviral drug regimens and the development of new drugs are challenging issues in HIV chemotherapy.
Menéndez-Arias
Luis
L
Centro de Biologi;a Molecular Severo Ochoa, Consejo Superior de Investigaciones Cienti;ficas-Universidad Autónoma de Madrid, Cantoblanco, 28049, Madrid, Spain. lmenendez@cbm.es
D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D004352:Drug Resistance, Microbial; D006678:HIV / Q000187:drug effects*; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology; D017320:HIV Protease Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors; D006801:Humans; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase