Stavudine (D4T, ZERIT™) is a nucleoside analog reverse transcriptase(RT) inhibitor of HIV RT that is approved for use in children and adults with symptomatic HIV infection unresponsive to prior therapy. We determined the pre-treatment IC50 (concentration of drug that inhibits 50% viral replication) for D4T in both a treatment naive and treatment experienced group of HIV positive children. IC50s were also determined after D4T monotherapy was initiated in the treatment experienced group.
A peripheral blood mononuclear cell (PBMC) based anti-retroviral resistance assay was performed for determination of D4T IC50 on 89 clinical isolates. The clinical isolates were obtained from HIV positive children followed by the Duke University Pediatric Infectious Disease Clinic. Twenty-nine clinical isolates obtained from eleven patients with no history of prior anti-retroviral therapy were used to determine mean IC50 for D4T. The clinical isolates were obtained from time points varying from 1 to 27 months prior to starting therapy with D4T. Six of the eleven patients had more than one clinical isolate available for calculation of IC50s. The mean IC50 for D4T in patients prior to anti-retroviral therapy was 1.06μM± 1.21.
