Format

Send to

Choose Destination
AIDS Res Hum Retroviruses. 2008 Jul;24(7):925-9. doi: 10.1089/aid.2008.0043.

Enhancement of HIV infection by cellulose sulfate.

Author information

1
Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.

Abstract

Cellulose sulfate, a polyanionic compound derived from cotton, has been proposed as a topical microbicide to reduce the sexual transmission of HIV. However, a phase III clinical trial of a vaginal gel formulation of cellulose sulfate (Ushercell) had to be prematurely closed after early data indicated microbicide users had a higher rate of HIV infection than women using a placebo. The unexpected results of the cellulose sulfate trail prompted us to reexamine and attempt to replicate the available preclinical data for this compound and other polyanions. We show here that cellulose sulfate has a biphasic effect on HIV infection in vitro: at high concentrations it inhibits infection but at low concentrations it significantly and reproducibly increases HIV infection. This stimulatory effect is evident for the R5-tropic strains of virus responsible for sexual transmission, reflects the rate of infection rather than viral growth, and occurs at clinically relevant concentrations of the compound. An examination of published studies shows that the biphasic effect of cellulose sulfate was evident in previous research by independent laboratories and is also found for other polyanions such as dextrin sulfate and PRO2000. These data help in understanding the failure of the Ushercell clinical trial and indicate that cellulose sulfate is not safe for mucosal application in humans.

PMID:
18627218
PMCID:
PMC2927036
DOI:
10.1089/aid.2008.0043
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Atypon Icon for PubMed Central
Loading ...
Support Center