"Molecular Condom" Gel That Blocks HIV

Developed By Scientists
US scientists have developed an HIV-blocking gel made from a polymer that women
can use as a vaginal "molecular condom": the gel becomes semi-solid in the
presence of semen and traps the AIDS-causing virus in its microscopic mesh.
However it will be several years before the gel is available since clinical trials in
humans would have to be done first.

The new material was developed by scientists at the University of Utah in Salt Lake
City. A paper about how they tested the gel and how it traps HIV particles will be
published online later this week in the journal Advanced Functional Materials. Co-
authors include researchers from Northwestern University in Chicago who helped
track the movement of HIV in the gel.

The paper's senior author Dr Patrick Kiser, an associate professor of bioengineering

at the University of Utah's College of Engineering, told the press that:

"The first step in the complicated process of HIV (human immunodeficiency virus)
infection in a woman is the virus diffusing from semen to vaginal tissue."

We want to stop that first step. We have created the first vaginal gel designed to
prevent movement of the AIDS virus. This is unique. There's nothing like it," he
added.

Kiser explained that they wanted to develop technologies that enabled women to
protect themselves against HIV without having to persuade their partners to do it.
He said this was important in the under-resourced countries like sub-Sahara Africa
and south Asia where in some areas the rate of HIV infection among women is as
high as 60 per cent.

First author Julie Jay, who is working toward a doctorate in pharmaceutics and
pharmaceutical chemistry at the university said:

"Due to cultural and socioeconomic factors, women often are unable to negotiate
the use of protection with their partner."

She explained that she, Kiser, and the rest of the team developed a vaginal gel that
the woman would insert a few hours before sex. The gel detects the presence of
semen and acts as a barrier between HIV and vaginal tissue, effectively stopping
the virus from infecting vaginal cells.

"We wanted to build a gel that would stop HIV from interacting with vaginal tissue,"
said Kay.

The effort to develop a range of intravaginal gels, rings and films to prevent the
spread of AIDS is not new but it has reached an impasse: few have reached clinical
trials in Africa, and those have failed to stop virus transmission. This was either
because the anti-virals they were delivering were too weak or did not last long
enough, or because patients just didn't use them. Also, some of the gels increased
the risk of transmission, possibly because they irritated the lining of the vagina,
causing immune cells to concentrate in that area, which were then successfully
targeted by the virus.

Kiser and colleagues have been working to develop a "molecular condom" for some
years. In 2006 they published a paper on an earlier type of gel that was applied to
the vagina as a liquid that became a gel at body temperature, and then became
liquid again in the presence of semen, whereupon it released an anti-HIV drug.

But the problem with this earlier attempt was that in Africa, the high ambient
temperatures stopped the gel from becoming liquid again, which stopped it coating
the vaginal lining evenly. Also, there aren't many antivirals that bind and attack HIV
in the presence of semen.

So Kiser and colleagues went back to the drawing board. This time they came up
with a new gel that works in the opposite way to the old one. The new gel responds
to changes in pH (acidity or alkalinity) so that when it comes into contact with the
less acidic semen it becomes a semi-solid instead of more liquid, and also forms a
network of interlinked molecules like a mesh.

The gel is made of two polymers, PBA (phenylboronic acid) and SHA
(salicylhydroxamic acid). Polymers are repeating patterns of long chain-like
molecules, like chemical "spaghetti". In this case, imagine one type of spaghetti is
made of PBA and the other is made of SHA, that under the normal acidity inside the
vagina, where pH is around 4.8, the bonds between them are weak so the strands of
spaghetti slip and slide around each other easily: and the gel remains a gel.

But when the environment becomes less acidic, and becomes increasingly alkaline,
at around pH of 7.6, which is what the vaginal environment becomes in the
presence of semen, the spaghetti strands of PBA and SHA stick together much more
strongly, and the gel becomes semi-solid.

As Jay explained:

"It flows at a vaginal pH, and the flow becomes slower and slower as pH increases,
and it begins to act more solid at the pH of semen."
The scientists at Northwestern University in Chicago tracked the movement of the
HIV in the gel. They marked the virus with a fluorescent dye and followed it with a
sophisticated microscope and saw how its speed changed under different pH
conditions.

Also, HIV moves slowly in the gel, even when the pH is low (acid) and the spaghetti
strands of the two polymers are still slippery. However, the virus stops moving
completely when pH is higher.

This is because the size of the mesh, the holes in the net, formed by the polymers
as they bond to each other under higher pH is around 30 to 50 nanometers, while
the HIV particle is about 100 nanometres wide.

It's like catching pebbles with a tennis racket: the holes formed by the racket strings
(the mesh) are just small enough to stop the stones (the HIV) falling through. To
imagine how small this is, a human hair is 100,000 nanometers thick: in the tennis
racket analogy, that would be about the size of the tennis court.

Kiser said they think the gel should block other viruses and sperm: perhaps it could
be used as a contraceptive, or to stop infections by herpes viruses and HPV, the
human papillomavirus that causes cervical cancer.

Taking the concept further, if the gel stops the HIV getting into cells, then perhaps it
can also act as a barrier against immune cells getting near HIV. AIDS develops when
HIV hijacks immune system cells.

Kiser said another option would be to add anti-AIDS drugs like tenofovir to the gel.
Tenofovir is not like the antivirals they tested with the old gel, it protects immune
cells from infection.

"The virus would have two barriers to get through: the polymer barrier and then the
drug barrier," he explained.

After sex, any residual HIV particles would become inactive because the vagina
would return to normal acidity, which they don't like, and the remaining antiviral in
the gel would still work as a barrier to some extent.

The researchers hope that human trials will start in three to five years, and then the
gel will be available a few years after that. They want the gel to contain antivirals
that both block HIV and stop it replicating.

Sources: University of Utah.

Written by: Catharine Paddock, PhD
Copyright: Medical News Today

Website: http://www.medicalnewstoday.com/articles/160259.php

Huge challenges ahead in fight

against AIDS

Leading health experts called for repeal of outdated laws criminalizing

prostitution and homosexuality so that people suffering from HIV/AIDS or at
risk from the disease could get medical treatment.

"The main challenge is overcoming the whole issue of stigma and

discrimination, repealing of outdated laws and legislation that countries have
got," Prasada Rao, director of UNAIDS Asia Pacific regional support team,
said on the margins of an HIV/AIDS conference.

Rao and other experts, kicking off a four-day meeting, said that while
progress has been made in research and getting people treated for AIDS,
huge challenges lie ahead and much more needs to be done.

"All this progress is not meaningful if we don’t address the stigma and
discrimination in this region. Young children (whether infected themselves or
have family members who are infected) or are still being evicted from
schools," Rao told the conference.

"This must change. Without this, progress is not possible," he added.

After HIV/AIDS was first identified in the early 1980s it unleashed fear and a
strong wave of prejudice against high-risk groups such as gay and bisexual
men and prostitutes, but little appears to have changed after more than 20
years.
Everywhere around the world, criminalization of behavior involving illicit drug
use, sex work and sex between men is seriously hampering effective
prevention and support programs, according to experts working to help
these people.

"For gay men, we need to reach out to these people but if their behavior is
criminalized, they are not going to come to you and say hey I need help. This
is a classic case of a clash between public health and public security," said
Loretta Wong, who heads the Hong Kong-based help group AIDS Concern.

"If they don’t get access to services and treatment, their health cant be
monitored, they wont get tested. They will instead be driven underground
and there will be the risk of infections increasing," she added.

More treatment, money needed

The conference also heard strong calls for more access to treatment. Women
and children were particularly left out of the loop, experts said.

"We are supposed to be achieving universal access by 2010. We are not

going to make these goals particularly in treatment, said David Cooper,
professor of medicine and director at the National Centre in HIV
Epidemiology and Clinical Research in Sydney.

Although about three million people were receiving drugs to control HIV by
the end of 2007, or nearly 950,000 more compared with the end of 2006,
only 31% of people who were in need of drugs were getting them.

Cooper said children and pregnant women in low and middle-income

countries need better and adequate drugs.

"There is incontrovertible new evidence that treating women with

antiretroviral therapy in pregnancy and during their breastfeeding period will
almost eliminate HIV infection in their infants."

"But we are not getting access to these women and we are not treating them
with proper antiretroviral therapy. We are just giving them single-dose
drugs," Cooper said.

Published: 10:17PM Monday August 10, 2009

Source: Reuters
Website: http://tvnz.co.nz/health-news/huge-challenges-ahead-in-fight-against-aids-
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