STAVUDINE(D4T, ZERIT™) SENSITIVITIES IN CLINICAL HIV ISOLATES OBTAINED FROM A PEDIATRIC POPULATION. • 1029

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. IC_50s 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 IC_50s. The mean IC₅₀ for D4T in patients prior to anti-retroviral therapy was 1.06μM± 1.21.

Twenty-seven isolates from five patients who had been on previous nucleoside analogs were available for PBMC assay and IC₅₀ calculation. Clinical isolates from the five patients represented time points from 1-55 months prior to starting D4T therapy. The mean IC₅₀ for the treatment experienced group was 1.68 ±1.54μM. Thirty-three isolates representing six patients who had received previous nucleoside analog therapy were available for PBMC assay after D4T monotherapy was instituted. The mean value was 2.30 ± 1.91μM.

No significant difference (students t-test, p=0.10) was noted between the pre-D4T IC₅₀ in the treatment naive and treatment experienced groups of HIV positive children. The pre-treatment D4T IC₅₀ in the treatment experienced group was not significantly different from post-treatment values(t-test, p=0.2). Previous nucleoside analog therapy did not seem to alter D4T IC_50s in pediatric patients currently receiving D4T monotherapy.