INHIBITION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 REVERSE-TRANSCRIPTASE BY DEGRADATION PRODUCTS OF CEFTAZIDIME

Previous work by Hafkemeyer et al. (1991) [Nucleic Acids Research 19: 4059-4065] indicated that a degradation product of ceftazidime, termed HP 0.35, was active against the RNase H activity of human immunodefic iency virus type 1 (HIV-1) and feline immunodeficiency virus (FIV) rev erse transcriptase (RT) in vitro. Attempting to repeat these results, we isolated HP 0.35 from an aqueous degradation of ceftazidime and, af ter careful purification, we found HP 0.35 to be essentially inactive against both the polymerase and RNase H domains of HIV-1 Ri (IC50 of > 100 mu g mL(-1)). During the investigation we discovered that polymeri c degradation products of ceftazidime inhibited both the polymerase an d, to a greater extent, the RNase H activities of HIV-1 Ri in vitro (I C50 approximately 0.1 and 0.01 mu g mL(-1), respectively). Subjecting HP 0.35 to conditions under which it could polymerize induced inhibito ry activity similar to that of the polymeric ceftazidime degradation p roducts. it is proposed that the previously reported activity of HP 0. 35 may have resulted from the presence of low levels of polymeric mate rial either from incomplete purification or From polymerization of HP 0.35 during storage or in vitro testing.