Important note: Information in this article was accurate in 1998. The state of the art may have changed since the publication date.
Reduction of the viral load of HIV-1 after the intraperitoneal administration of dextrin 2-sulphate in patients with AIDS.
AIDS. 1998 Mar 5;12(4):399-409. Unique Identifier : AIDSLINE MED/98178992 Shaunak S; Thornton M; John S; Teo I; Peers E; Mason P; Krausz T; Davies DS; Department of Infectious Diseases, Imperial College School of; Medicine, Hammersmith Hospital, London, UK.
Abstract:
OBJECTIVE: To determine the safety and efficacy of the sulphated polysaccharide, dextrin 2-sulphate, when delivered to the lymphatic circulation by the peritoneal route. DESIGN: An open Phase I/II dose-escalation clinical study in which six patients with AIDS were treated with seven courses of dextrin 2-sulphate each lasting 1 month. METHODS: During each course of treatment, the drug was administered daily for 28 days using an intraperitoneal catheter. Viral load was measured at frequent intervals using a plasma tissue culture infectious dose (TCID) assay, a cellular TCID assay, p24 antigenaemia, HIV-1 RNA and HIV-1 DNA. Plasma beta-chemokine levels were also measured. RESULTS: Dose escalation was completed without toxicity. A total of 7 patient-months of treatment were completed. With increasing doses of dextrin 2-sulphate, the infectious plasma viraemia, cellular viraemia and p24 antigenaemia all fell during the period of drug administration, but with no significant change in HIV-1 RNA. This was associated with increased plasma levels of macrophage inflammatory protein (MIP)-1alpha and MIP-1beta. Dextrin 2-sulphate accumulated in peritoneal macrophages and induced the release of MIP-1alpha and MIP-1beta from these cells in vitro. These 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 viraemia, cellular viraemia, p24 antigenaemia and HIV-1 RNA was seen at day 100 which was then sustained for several months. A clinical improvement in Kaposi's sarcoma was also seen. CONCLUSIONS: Our results suggest that the intraperitoneal administration of dextrin 2-sulphate can reduce the replication of HIV-1 in patients with AIDS. With increasing doses of dextrin 2-sulphate, the fall in viral load was seen during the period of drug administration and again 2 months after completing treatment.
Keywords: *Acquired Immunodeficiency Syndrome/DRUG THERAPY *Acquired Immunodeficiency Syndrome/VIROLOGY *Anti-HIV Agents/ADMINISTRATION & DOSAGE *Dextrins/ADMINISTRATION & DOSAGE *HIV-1/DRUG EFFECTS
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Important note: Information in this article was accurate in 1998. The state of the art may have changed since the publication date.
