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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 925-929 |
| Number of pages | 5 |
| Journal | AIDS Research and Human Retroviruses |
| Volume | 24 |
| Issue number | 7 |
| DOIs | |
| State | Published - Jul 1 2008 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Immunology
- Infectious Diseases
- Virology
Cite this
Short communication : Enhancement of HIV infection by cellulose sulfate. / Wang, Tao; Richards, Chris; Hamer, Dean.
In: AIDS Research and Human Retroviruses, Vol. 24, No. 7, 01.07.2008, p. 925-929.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Short communication
T2 - Enhancement of HIV infection by cellulose sulfate
AU - Wang, Tao
AU - Richards, Chris
AU - Hamer, Dean
PY - 2008/7/1
Y1 - 2008/7/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=48749086467&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=48749086467&partnerID=8YFLogxK
U2 - 10.1089/aid.2008.0043
DO - 10.1089/aid.2008.0043
M3 - Article
C2 - 18627218
AN - SCOPUS:48749086467
VL - 24
SP - 925
EP - 929
JO - AIDS Research and Human Retroviruses
JF - AIDS Research and Human Retroviruses
SN - 0889-2229
IS - 7
ER -