T cells from human immunodeficiency virus (HIV)-infected individuals undergo spontaneous and activation-induced ex vivo apoptosis. Here we report that peripheral blood mononuclear cells (PBMCs) obtained from six HIVinfected individuals exhibited reduced ex vivo DNA fragmentation and cell death after ingestion of all-trans-retinoic acid (tRA). These effects were attenuated with continued daily RA administration, which correlated with a >5-fold decrease in serum peak RA concentrations. Incubation of PBMCs from HIV+ individuals with tRA in vitro resulted in decreased DNA
An intermittent schedule of ATRA administration results in repetitive periods of exposure to concentrations of ATRA normally only observed on the first day of treatment. Phase II trials to evaluate the role of intermittent schedules of administration for ATRA are planned.
Intermittent ATRA therapy was reasonably well tolerated and provided a means to circumvent the low plasma exposure found with continuous ATRA therapy. However, we were unable to document antitumor activity in patients with HIV-associated KS.
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