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 inhibitor HEY 097 was investigated in asymptomatic or mildly symptomatic human immunodeficiency virus (HIV)-1-infected patients in a randomized, double-blinded, dose-escalation study. Mean maximum virus load decreases ranged from -1.31 log(10) copies/ml of plasma at week 1 in the group receiving HEY 097 monotherapy (250 mg three times daily) to -2.19 log(10) copies/ml at week 4 in the group receiving zidovudine plus HEY 097 (750 mg three times daily). After 12 weeks, these patients had viral RNA copy numbers 1.05 log(10) below baseline. Genotypic analysis of resistance development revealed reverse transcriptase K103N variants in most patients, which was associated with less durable efficacy of HEY 097 treatment. Fewer patients receiving combination 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 activity can be expected from multiple combination therapy regimens including a quinoxaline derivative.