Human immunodeficiency virus type 1 (1IV-1) strains were Isolated from nine patients before and after prolonged therapy with either an alternating regimen of 3'-azido-3'-deoxythymidine (AZT) and 2',3'-dldeoxycytldin (ddC) (AZT/ddC) or 2',3'-deoxyinosine (ddl) alone. AN strains obtained from four patients who received AZT/ddC for up to 41 mo were highly insensitive to AZT in vitro. Only one strain obtained after AZT/ddC therapy showed reduced susceptibility to ddC in addition to AZT and had previously unreported amino acid substitutions in the viral polymeraseending pol region, whereas three other strains had one or more of the five previously reported AZT-related mutations. In flve HIV-1 strains from patents who received ddI for up to 29 mo, no appreciable decrease in sensitivity to ddl was detect.Two strains Isolated after ddI therapy had no t amino acid mutations, although three strains had a mutation reportedly acited with ddI administration. These data suggest that HIV-1 develops reduced susceptibility to AZT more readily than to ddC and ddI and/or that the reduced susceptibility to ddC and ddI is modest in degree. Moreover, the present data suggest that an alternating regimen of AZT and ddC does not block the emergence of AZT-ensitve va . It should be noted, however, that the current results do not provide a basds for concluding that AZT/ddC or ddI is inferior, equivalent, or superior to AZT as therapy of AIDS.

No abstract

This unit presents an assay that has proven useful as an initial screening test is an HIV cytopathic effect (CPE) inhibition assay in which immortalized T cell lines (e.g., ATH8 or MT2) that are profoundly sensitive to the cytopathic effect of certain strains of HIV are utilized as target cells. Additional protocols assess the anti-HIV activity of certain candidate agents by measuring inhibition of syncytium formation or p24 gag protein production by ELISA. Calculation of the 50% inhibitory concentration (IC(50)) is also presented.

No abstract