title: Clinical utility of current NNRTIs and perspectives of new agents in this class under development.
abstract: Highly active antiretroviral therapy (HAART) has significantly reduced the number of deaths caused by AIDS. However, the antiviral efficacy of HAART comprising protease inhibitors (PIs) and nucleoside reverse transcriptase inhibitors (NRTIs) is frequently accompanied by a decrease in patients' quality of life. PI-based therapies often fail due to poor adherence caused by heavy pill burden, complex dosing schedules and undesirable side effects. The current trend is to switch from PI-based to PI-sparing regimens consisting of non-nucleoside reverse transcriptase inhibitors (NNRTIs) and NRTIs. Despite some encouraging results from NNRTI-containing therapies, two major concerns in using the currently available NNRTIs remain: 1) low genetic barrier to the emergence of resistance and 2) cross-resistance due to single mutations that often render the whole class of NNRTIs ineffective. Clearly, new and improved NNRTIs are needed to address these concerns.
authors.affiliation: Drug Discovery, Valeant Pharmaceuticals International, Costa Mesa, Calif., USA. zzhang@valeant.com
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Zhang
authors.forename: Robert
authors.initials: R
authors.lastname: Hamatake
authors.forename: Zhi
authors.initials: Z
authors.lastname: Hong
mesh_terms: D000480:Alkynes; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D048588:Benzoxazines; D003521:Cyclopropanes; D020008:Delavirdine / Q000494:pharmacology / Q000627:therapeutic use; D024882:Drug Resistance, Viral; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D015497:HIV-1 / Q000254:growth & development*; D006801:Humans; D019829:Nevirapine / Q000494:pharmacology / Q000627:therapeutic use; D010078:Oxazines / Q000494:pharmacology / Q000627:therapeutic use; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D017320:HIV Protease Inhibitors; D010078:Oxazines; D018894:Reverse Transcriptase Inhibitors; D019829:Nevirapine; D020008:Delavirdine; C098320:efavirenz