In a phase III blinded study, 1200 patients with CD4+ cell counts (200-500 cells/µL) received zidovudine (ZDV) alone or in combination with one of three doses (200, 300, or 400 mg TID) of delavirdine (DLV). The phenotypic sensitivity of viral isolates from more than 190 randomly selected patients was evaluated at predose and weeks 12 and 24 of treatment. After six months of ZDV monotherapy, 14% of patient isolates were moderately to fully resistant to ZDV (IC(50) greater than 0.2 micromolar). In contrast 100% of isolates from patients receiving 400 mg DLV + ZDV remained highly sensitive to ZDV after 24 weeks of therapy. DLV sensitivity in 88% of these isolates remained below median trough levels (8.3 micromolars) of DLV achieved in these patients. In a phase II DLV + ZDV trial with ZDV experienced patients, viral isolates demonstrated resensitization to ZDV with an average 85 fold decrease in the ZDV IC(50) during the first six months of therapy. These data suggest that exposure to DLV + ZDV combination regimens results in a viral population with increased or maintained sensitivity to ZDV and prolonged sensitivity to DLV.
Keywords: AEGIS, Zidovudine, Delavirdine, HIV-1, Anti-HIV Agents, Reverse Transcriptase Inhibitors, CD4 Lymphocyte Count, HIV-1 Reverse Transcriptase, HIV Protease Inhibitors, Human, virology, AIDS
