HIV Protease Inhibitor PNU-140690 Shows Synergy With Ritonavir
An evaluation of PNU-140690, a nonpeptidic inhibitor of HIV-1 protease currently under investigation, indicates that this compound may be therapeutically useful when administered in combination regimens with ritonavir, according to Pharmacia & Upjohn researchers.
Drs. K.-T. Chong and P.J. Pagano of Pharmacia & Upjohn, describe their studies of combinations of PNU-140690 and ritonavir on the replication of clinical isolates of HIV-1 in peripheral blood mononuclear cells. The isolates were ritonavir-sensitive and ritonavir-resistant.
The isolates exhibited no significant difference in sensitivity to PNU-140690. However, following mathematical analysis, the researchers found that the combination of various concentrations of PNU-140690 with ritonavir yielded additive to moderately synergistic antiviral effects against the ritonavir-sensitive isolate and stronger synergy against the ritonavir-resistant isolate. They detected no significant antagonism associated with any of the combinations.
The researchers concluded that PNU-140690 may be useful in combination regimens with a structurally unrelated protease inhibitor such as ritonavir.
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