Antiviral activity of the human immunodeficiency virus type 1 specific nonnucleoside reverse transcriptase inhibitor HBY097 alone and in combination with zidovudine in a phase II study

The safety and antiviral activity of the second-generation nonnucleoside in hibitor HEY 097 was investigated in asymptomatic or mildly symptomatic huma n immunodeficiency virus (HIV)-1-infected patients in a randomized, double- blinded, dose-escalation study. Mean maximum virus load decreases ranged fr om -1.31 log(10) copies/ml of plasma at week 1 in the group receiving HEY 0 97 monotherapy (250 mg three times daily) to -2.19 log(10) copies/ml at wee k 4 in the group receiving zidovudine plus HEY 097 (750 mg three times dail y). After 12 weeks, these patients had viral RNA copy numbers 1.05 log(10) below baseline. Genotypic analysis of resistance development revealed rever se transcriptase K103N variants in most patients, which was associated with less durable efficacy of HEY 097 treatment. Fewer patients receiving combi nation therapy with high-dose HEY 097 developed the K103N variant (P < .01) , HBY 097 caused pronounced acute suppression of HIV-1 replication both in combination with zidovudine and alone, Therefore, sustained antiviral activ ity can be expected from multiple combination therapy regimens including a quinoxaline derivative.