Trial Information

Retrospective Analysis of HIV-1 RNA Levels in Pediatric HIV-Infected Patients Treated With Didanosine

This study will examine clinical and immunologic data and HIV-1 RNA levels in banked serum
specimens from HIV-infected pediatric patients previously enrolled on NCI protocol
88-C-0219, a phase I/II study of 2', 3'-dideoxyinosine (ddI). In the original study serum
p24 antigen was used as the direct measurement of viral quantitation. Advances in
understanding of HIV pathophysiology have demonstrated that HIV-1 RNA level as measured by
quantitative RNA PCR is a far superior molecular tool for assessing viral replication and
burden in vivo. Analysis of clinical, HIV-1 RNA and CD4 responses will be performed to
identify patients with discordant surrogate marker responses to therapy, defined as:
improvement in immunologic parameters in the setting of virologic non-response or failure.
Correlation will then be made with short and long term clinical outcomes.

Following the initial analysis to identify patients with discordant responses, selenium
levels, viral genotypic and phenotypic profiles of resistance to ddI, and in vitro viral
fitness will be examined. These biologic parameters have recently been determined to
potentially play an important role in clinical, immunologic and virologic HIV-related
outcomes. Parameters will be examined in subsets of patients with the following surrogate
marker response profiles: a.) immunologic and virologic responders; b.) immunologic and
virologic non-responders; and c.) discordant immunologic and virologic responders.
Specimens from the ddI monotherapy study were chosen for this analysis because a substantial
body of clinical and immunologic data is available on patients up to 7 years.