REDUCTION OF THE VIRAL LOAD OF HIV-1 AFTER THE INTRAPERITONEAL ADMINISTRATION OF DEXTRIN 2-SULFATE IN PATIENTS WITH AIDS

Objective: To determine the safety and efficacy of the sulphated polys accharide, dextrin 2-sulphate, when delivered to the lymphatic circula tion by the peritoneal route. Design: An open Phase I/II dose-escalati on clinical study in which six patients with AIDS were treated with se ven courses of dextrin 2-sulphate each lasting 1 month. Methods: Durin g each course of treatment, the drug was administered daily for 28 day s using an intraperitoneal catheter. Viral load was measured at freque nt intervals using a plasma tissue culture infectious dose (TCID) assa y, a cellular TCID assay, p24 antigenaemia, HIV-1 RNA and HIV-1 DNA. P lasma beta-chemokine levels were also measured. Results: Dose escalati on was completed without toxicity. A total of 7 patient-months of trea tment were completed. With increasing doses of dextrin 2-sulphate, the infectious plasma viraemia, cellular viraemia and p24 antigenaemia al l fell during the period of drug administration, but with no significa nt change in HIV-1 RNA. This was associated with increased plasma leve ls of macrophage inflammatory protein (MIP)-1 alpha and MIP-1 beta. De xtrin 2-sulphate accumulated in peritoneal macrophages and induced the release of MIP-1 alpha and MIP-1 beta from these cells in vitro. Thes e beta-chemokines could have augmented the cell surface-mediated anti- HIV-1 effect of dextrin 2-sulphate in vivo by binding to and blocking the CC-chemokine receptor-5. A second fall in infectious plasma viraem ia, cellular viraemia, p24 antigenaemia and HIV-1 RNA was seen at day 100 which was then sustained for several months. A clinical improvemen t in Kaposi's sarcoma was also seen. Conclusions: Our results suggest that the intraperitoneal administration of dextrin 2-sulphate can redu ce the replication of HIV-1 in patients with AIDS. With increasing dos es of dextrin 2-sulphate, the fall in viral load was seen during the p eriod of drug administration and again 2 months after completing treat ment. (C) 1998 Rapid Science Ltd.