Anti-HIV activity of amphotericin B-cholesteryl sulfate colloidal dispersion in vitro

We examined whether the anti-HIV-l activity of the polyene antibiotic Ampho tericin B (AMB) is retained following incorporation into sterically stabili zed 'Stealth' liposomes (L-AMB) with prolonged circulation in vivo, or chol esteryl sulfate colloidal dispersions (CD-AMB). The effects of the differen t preparations on acute infection of H9 cells with HIV-1(IIIB), spreading o f the virus from chronically infected H9/HTLV-IIIB cells to SupT1 cells, an d HIV-l-induced syncytium formation were evaluated. Infection was monitored by p24 levels in culture supernatants. L-AMB did not affect HIV-I infectio n. When present only during initial infection, AMB (3-20 mu g/ml) reduced p 24 levels by 70-80% after 7 and 10 days post-infection, while CD-AMB inhibi ted p24 production by similar to 30-40% at day 7 and 50-60% at day 10. The inhibitory effect of CD-AMB and AMB was enhanced by continuous treatment of acutely infected cells. The reduction of p24 production during continuous treatment was not due to cytotoxicity. During spreading of infection from i nfected to uninfected cells, AMB almost completely inhibited virus producti on while CD-AMB reduced both p24 production and the cytopathic effect in a dose-dependent manner. HIV-I induced syncytium formation was slightly inhib ited by AMB but not by CD-AMB. Because CD-AMB is considerably less cytotoxi c than AMB, its ability to inhibit HIV infection in vivo needs to be evalua ted further. (C) 1999 Elsevier Science B.V. All rights reserved.