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Date Posted: 20:18:47 07/24/02 Wed
Author: moonotter
Subject: New HIV Microbicide Candidates Show Promise in Preclinical Studies

New HIV Microbicide Candidates Show Promise in Preclinical Studies




By Deborah Mitchell
BARCELONA, Spain (Reuters Health) Jul 10 - Two new compounds are showing promise for use as topical vaginal and anal HIV microbicides, according to presentations delivered here on Wednesday at the XIV International AIDS Conference.

"Any HIV topical microbicide has to be safe--there is very, very little room for toxicity," Dr. Mary Klotman of Mount Sinai School of Medicine in New York told conference attendees.

One such potential compound is "SAMMA," a polymer derived from sulfuric acid treatment of mandelic acid. The agent is not a surfactant and it is not sulfated, making it less likely to damage the vaginal epithelium and flora. SAMMA is also colorless, odorless and inexpensive to produce, important features for a candidate microbicide, she said.

In in vitro experiments, Dr. Klotman and her colleagues evaluated the activity and toxicity of SAMMA combined with clinical isolates of HIV and primary cell culture systems including human cervical cells, macrophages and T cells. They also tested SAMMA with cells engineered to express single HIV coreceptors.

In dose ranges of 10 to 100 micrograms per milliliter, SAMMA blocked laboratory-adapted and primary isolates of HIV in primary cells. SAMMA also blocked infection with R5 and X4 HIV isolates.

In addition, SAMMA effectively blocked HIV binding to cells and glycoprotein gp120. Similar effects were observed with herpes simplex virus. No measurable toxicity was seen.

"SAMMA inhibits both laboratory-adapted and primary isolates of HIV," Dr. Klotman concluded. This compound shows little or no cytotoxicity, has an "excellent selectivity index" and merits further evaluation, she added.

In a second study, a topical microbicide containing the nonnucleoside reverse transcriptase inhibitor dapivirine (TMC120) was able to completely inhibit vaginal transmission of HIV in a mouse model.

This the first in vivo evidence that an NNRTI is feasible as a HIV microbicide, according to Dr. Simonetta Di Fabio of the Istituto Superiore di Sanita in Rome. Dr. Di Fabio presented her teams' data from a hu-SCID mouse model developed to simulate in vivo vaginal transmission of HIV.

After a single vaginal application with 25 mL of a gel containing dapivirine, 21 female mice were challenged with human peripheral blood lymphocytes infected with a laboratory strain of HIV.

Rates of protection were 70% to 80%, Dr. Di Fabio told conference participants. When the gel was adjusted to reduce its viscosity, the rates of protection reached 100%. Because of the marked improvement seen after the gel viscosity was reduced, "the findings suggest that distribution is an important factor," she added.



Related Links
Conference Coverage
XIV International AIDS Conference


External Links
News From the XIV International AIDS Conference


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Reuters Health Information 2002. © 2002 Reuters Ltd.
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