A fusion inhibitor (FP-21399) for the treatment of human immunodeficiency virus infection: A phase I study

FP-21399 is a bis(disulfonaphthalene) derivative that prevents human immuno deficiency virus (HIV) infection of uninfected cells by blocking entry of t he virus. FP-21399 shows an affinity for lymph nodes. In this phase I study , FP-21399 was administered intravenously over 1 h as a single dose (0.9, 1 .7, 2.8, and 4.2 mg/kg) or as a once-weekly infusion (1, 2, and 3 mg/kg) fo r 4 consecutive weeks to 34 HIV-1 infected patients with CD4(+) cell counts of 50-400 cells/mu L. Concomitant antiretroviral therapy was permitted but not required. The most frequent adverse events involved the transient, dos e-dependent appearance of drug- or metabolite-related color in the urine an d skin. Plasma drug levels were linear with dose. The drug was cleared, wit h an elimination half-life of 4 h and a terminal half-life of 1.5-2 days; t he terminal half-life represented redistribution and clearance from tissues . FP-21399 administered weekly for 4 weeks was well tolerated. Further stud ies are necessary to define the role of this fusion inhibitor in the treatm ent of HIV infection.