Anti-HIV activity of amphotericin B-cholesteryl sulfate colloidal dispersion in vitro.
We examined whether the anti-HIV-1 activity of the polyene antibiotic Amphotericin B (AMB) is retained following incorporation into sterically stabilized 'Stealth' liposomes (L-AMB) with prolonged circulation in vivo, or cholesteryl sulfate colloidal dispersions (CD-AMB). The effects of the different preparations on acute infection of H9 cells with HIV-1IIIB, spreading of the virus from chronically infected H9/HTLV-IIIB cells to SupT1 cells, and HIV-1-induced syncytium formation were evaluated. Infection was monitored by p24 levels in culture supernatants. L-AMB did not affect HIV-1 infection. When present only during initial infection, AMB (3-20 microg/ml) reduced p24 levels by 70-80% after 7 and 10 days post-infection, while CD-AMB inhibited p24 production by approximately 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 infected to uninfected cells, AMB almost completely inhibited virus production while CD-AMB reduced both p24 production and the cytopathic effect in a dose-dependent manner. HIV-1 induced syncytium formation was slightly inhibited by AMB but not by CD-AMB. Because CD-AMB is considerably less cytotoxic than AMB, its ability to inhibit HIV infection in vivo needs to be evaluated further.
Konopka
K
K
Department of Microbiology, University of the Pacific School of Dentistry, San Francisco, CA 94115, USA.
Guo
L S
LS
Düzgüneş
N
N
D000666:Amphotericin B / Q000494:pharmacology*; D019380:Anti-HIV Agents / Q000494:pharmacology*; D002788:Cholesterol Esters / Q000494:pharmacology*; D003102:Colloids / Q000494:pharmacology; D004337:Drug Carriers; D015726:Giant Cells; D015497:HIV-1 / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008081:Liposomes; D014407:Tumor Cells, Cultured
D019380:Anti-HIV Agents; D002788:Cholesterol Esters; D003102:Colloids; D004337:Drug Carriers; D008081:Liposomes; D000666:Amphotericin B; C007045:cholesteryl sulfate