A short-term clinical evaluation of L-697,661, a non-nucleoside inhibitor of HIV-1 reverse transcriptase

The pyridinone non-nucleoside reverse transcriptase inhibitor L-967,661 shows significant dose-related activity against HIV-1 and is also well tolerated by patients, but the rapid emergence of resistant strains of the virus may limit the effectiveness of this and other non-nucleoside reverse transcriptase inhibitors. The non-nucleoside reverse transcriptase inhibitors are atypical antiretroviral agents with selective activity in vitro against human immunodeficiency virus type 1 (HIV-1). They perform through direct inhibition of reverse transcriptase and are not incorporated into DNA. However, in vitro studies have indicated additive or synergistic activity between nucleoside and non-nucleoside antiretroviral agents. These agents may continue to be useful in combination regimens. When the genetic complexity of the virus is extensive and subpopulations of resistant virus are more probable, the use of non-nucleoside agents for very early infection or post-exposure prophylaxis may be especially beneficial.