KISS AND GEL
By Stacie Stukin
Sara and Paul
are like countless
married couples in the developing
world. While she raises children and
looks after livestock on a farm in rural
Zimbabwe, he works a subsistence-
wage job in a distant town.
They see each other, at best, once a
month. The last time Paul came
home, Sara noticed a vaginal discharge
just days after he left. A local
clinic confirmed her suspicion - Paul
had given her a sexually transmitted
infection. But when she tried to get
him to wear a condom, she recieved
a severe beating.
If 20 years of AIDS have taught
us anything, it's that men, straight
or gay, rich or poor, would sooner
chuck a condom than slip it on. In
sub-Saharan African countries, condom
use falls as low as 7 percent.
Nearly half of gay American men in
their 20s report that they recently
had unprotected anal sex. "I don't
think it's hard to ask someone to
wear a condom, but guys hate
them," says Dyanne Stempel, a
single white female living in Los
Angeles. "They don't say anything
and then they either can't perform
or they get uncomfortable."
But what if Sara and Dyanne had
a stealth method of protection?
Something called, let's say, Coochie
Cream or Booty Butter- an odorless
gel, lotion, foam or suppository that
could help protect them from STD's,
but that would also ensure the seamless
intimacy cherished in those passionate
moments? "It would be a
dream," Stempel says.
For 15 years, certain scientists,
gravely underfunded and mostly
dismissed by the AIDS research
mainstream, have toiled to make this
dream a reality. Now the fruit of
their labor is ripening, just as the
cause of women enters the vanguard
of AIDS conciousness. Their inventions
are called microbicides- and
while the unfortunate name sounds
like a fungus-eradication
product, if all goes well, these
woman controlled "chemical condoms"
could reach the over-thecounter
market in five years and
become the biggest reproductivehealth
innovation since the birth-control
pill.
"These
woman-controlled 'chemical condoms' could
reach the over-the-counter market in five years and
become the biggest reproductive-health
innovation since the birth-control pill."
No longer the
fantasy of
womanist policy wonks and heated
activists, microbicides have become a
cause celebre, splashed onto the
pages of publications like Vogue and
The Wall Street Journal. Their credibility
comes not only from the most
promising candidates' recent clinical
trial advances but also from the
stepped-up efforts of billionaire
philanthropists Bill and Melinda
Gates, who have donated a total of
$50 million to microbicide research.
In February, they made their most
recent contribution, $20 million to
fund a Phase III trial- the final, FDArequired
test of efficacy in humansof
a promising seaweed-based
product called Carraguard.
The need for such a revolutionary
product has become alarmingly
clear: Worldwide, 17.6 million
women have HIV. A single unprotected
sex act is eight times more
likely to infect a woman than a man.
Accross Africa and Asia, women in
ostensibly monogomous marriages
are at great risk of contracting HIV
and STD's. In Thailand, a study in
with their husbands. the Journal of
Acquired Immune Deficiency Syndromes
reported, 76 HIV positive
women said that their only sexual
contact was with their husbands.
"The issue of women has
come front and center in the AIDS
epidemic," says Helene Gayle, MD,
who championed women's prevention
programs as a top official at the
Centers for Disease Control and
Prevention and now oversees the
Gates Foundation's AIDS giving.
"The reality is, we're still many years
from having a vaccine, and that's
made people realize we need to
diversify research and development.
We can't just focus on treatments and
vaccines- we need to find intermediary
technologies."
Carraguard is just one of
nearly 60 microbicides in development
in the United States, India,
Brazil, Belgium and Britain. These
products come in a wide variety of
formulations. Some are contraceptive
as well as antimicrobial. Others
would allow for conception without
nixing HIV. Because of the prevalence
of anal sex, many researchers
insist that microbicides must work
rectally as well as vaginally. This has
the added bonus of making them
valuable to gay men as well as
straight women. But each prototype
aspires to a common goal: skin-toskin
contact, the ideal of intimacy
accross all cultures.
David Phillips, PhD, a senior
scientist at the Population Council,
wishes that he could say he's the
genius who discovered that a simple
red, seaweed-based product called
carrageenan prevents viral infections
such as HIV. But in fact, carrageenan,
a food thickener used in
Campbell's soups, ice cream and
baby food, has been known for its
antiviral properties since the '60s. In
the '80s, scientists began looking at
carrageenan's potential for herpes
prevention. That was when Phillips
began the research that led to the
formulation of Carraguard in the late
women alive
Spring '03 n Newsletter 9
'90s. "We've shown that
Carraguard is as effective against HIV
in the test tube and against several
sexually transmitted pathogens in animals,"
he says. "But there's still a lot
we don't know about how HIV gets
into the body. Now it's our job to prove
it will work with people."
Carraguard is one of five
microbicides set to enter advancedstage
clinical trials this year. With so
much riding on the results of the research,
scientists such as Zeda
Rosenberg, the interim executive director
of the International Partnership on
microbicides at Family Health International,
has a barrage of urgent questions
to answer. Overseeing the Phase
III tests of two other top contenders,
PRO 2000 and BufferGel, Rosenberg is
helping to design studies with upward
of 8,000 women. As far as the sheer
scale and ambition go, Rosenberg
maintains an upbeat attitude. "Every
challenge can be overcome with creative
design and lots of resources," she
says.
But the investigations are
starting with a financial straitjacket.
Carraguard, for instance, has only
about $20 million in its research coffer,
although conservative estimates put
the cost of a trial closer to $50 million.
Beyond the money, there are logistical
and ethical problems. Scientists can't
be in bed with participants when they
actually use the gel, so they must rely
on self-reporting rather than the datagathering
methods used in laboratorycontrolled
settings. Then there's the
moral dilemma that arises when Western
scientists give say, and African
woman-whose chances of contracting
HIV are 20 to 30 percent-a placebo gel
rather than the real thing. It's true that
the researchers will give all volunteers
condoms and encourage the use of
both latex and microbicide (or placebo
gel). But even the best intentions
could result in women being-or ultimately
feeling-exploited when their
risk of infection is frighteningly high.
Rosenberg acknowledges the ethical
implications but still defends the proceedings,
arguing that the women will
receive prevention and care at standards
comparable to those in the U.S.
"That means condom promotion and
counseling and treatment of STDs."
She says.
Rosenberg and her colleagues believe
that a microbicide will have demonstrated
efficacy if, over three years,
there are at least 30 percent fewer
infections among users than in the
control group. That may sound far
from ideal. But researchers at the London
School of Hygiene and Topical
Medicine estimate that a microbicide
with 60 percent effectiveness could
avert 2.5 million new HIV infections
over three years worldwide. On top
of the obvious human benefits, that
translates into a $2.7 billion savings in
health-care costs (not including HIV
meds) and $1 billion in productivity for
developing countries.
"This has been discussed by many
experts in the field, and there is some
consensus, at least for the first clinical
study, that 30 percent could potentially
lead to approval," says Debra
Birnkrant, MD, director of the FDA's
division of antiretroviral drugs, who
has reviewed every microbicide that
has entered trials. "This is being developed
globally-not just for the U.S.-
and if we could prevent 30 percent of
infections in Africa, that would be tremendous."
Still, she envisions the FDA
recommending the products for the
use with condoms. "The trials are being
conducted with them, and the labels
have to reflect that," she says.
Even with all the drum-rolling
about the promise of the "fab five"
microbicides, researchers have great
cause for caution. Two years ago,
four microbicide finalists had made it
to Phase III trials, but all ultimately
failed because they contained
Nonoxynol-9. In studies, the spermicide
was found to cause vaginal abrasions,
making women even more susceptible
to HIV.
The current crop works differently.
Carraguard's carrageenan belongs to
a family of compounds called sulfated
polymers, which are believed to coat
HIV and keep it from entering host
cells. BufferGel, made of a foaming
agent already used in many vaginal
products, mixes with the vagina's
natural acidity to create a pH level hostile
to HIV. Then there are
antiretroviral products like PMPA gel,
which work like current AIDS therapies
by blocking HIV replication. Since
the '80s, hundreds of compounds have
been screened in test tubes for their
ability to prevent pregnancy and kill
pathogens, says Henry L. Gabelnick,
PhD, the director of a microbicide research
consortium called CONRAD
that in 2000 received $25 million from
the Gates Foundation. After the devastating
failure of Nonosxynol-9, he
says, "people began looking for formulations
that were less irritating and
compounds that would bind the virus."
The finalists-mosts of which have
passed the small Phase II tests for
safety and initial indications of effectiveness-
all offer promising approaches.
The big problem now is
money. The Rockefeller Foundation
Microbicide Initiative, a working
group of consultants, researchers and
pharmaceutical analysts, estimates
that total product-development costs
for the first generation of microbicides
will run more than $750 million (by
contrast, the average drug, including
HIV medications, costs $500 million to
develop.) Sadly, the Initiative
"As
a society, we talk a lot more about therapy than prevention,"
says Kevin Whaley, PhD, who helped develop BufferGel.
"With microbicides, we're introducing a whole new
category, and that's just stunning to some people."
projects only
$230 million in public
funding for microbicide development
through the year 2005.
Once solution would be for deeppocketed
pharmaceutical giants to
partner with the current loose network
of academics, nonprofits and plucky,
indie biotechs such as ReProtect, the
Baltimore company that developed
BufferGel. But prevention has never
been Pharma's bread and butter. "As
a society, we talk a lot more about
therapy than prevention," says Kevin
Whaley, PhD, who helped develop
BufferGel. "With microbicides, were
introducing a whole new category, and
that's just stunning to some people."
To make matters worse, the female
condom and Today's Sponge, two
products seen as business-case precursors
to microbicides, were thought to
enjoy strong market potential but
turned out to be unmitigated flops.
Annual worldwide sales of the female
condom peaked at a miserable $6 million
(in comparison, "male" condom
sales have reached $295 million in the
U.S. alone), and the sponge raked in a
paltry $20 million-hardly the numbers
to justify microbicides' non-insignificant
development costs.
For the most part, pharmaceutical
giants are watching microbicide
testing from the sidelines and withholding
their wallets. Janet Skidmore,
a spokesperson for Merck, explains
that her company's HIV prevention
commitment lies, and will remain,
firmly in vaccine territory. "Given our
experience in the vaccine field, It's just
the more effective approach for us,"
she says. She denies that this decision
is based on economics or microbicides'
early clinical stumbles. "We feel
strongly that the best way to approach
this pandemic is with a vaccine."
But if Merck and its brethren were
in fact to consider the "return on investment"
numbers compiled by the
Rockefeller Foundation Microbicide
Initiative, they'd likely flee in horror.
While the group rates current
microbicides are as "promising" and
predicts that their global market size
could reach $900 million by 2011, it
places each candidate's statistical
chances of clinical approval and
market entry only at 25 percent. Even
worse, projections show that any corporate
backer of a first-generation microbicide
is likely to incur financial
losses in the tens of millions of dollars.
For a microbicide to be effective in the
developing world, it has to be cheap,
as little as 35 cents per dose-obliterating
profit margins.
Researchers and academics argue
that as long as the clinical trials are
publicly and philanthropically funded, a
pharmaceutical company
that owns or acquires a successful
microbicide does stand a chance to
make money. "It's not going to be a billion-
dollar blockbuster," Gabelnick
says. "But the market for spermicides
now is only $40 to $50 million, and that
hasn't kept personal-product companies
from selling them." He also envisions
a two-tier pricing system to balance
out the cheapness of microbicides
in poor countries. "People forget that
a cycle of oral contraceptives sells for
$30 in a pharmacy, but donor agencies
probably get them for 30 cents or less,"
he says, adding that in many developing
nations such as Brazil, India and
China, there's a sizeable, growing
middle class that can absorb a higher
price point.
That a viable, potentially lucrative
microbicide market exists in developed
coutries is something that UC/Berkeley
epidemiologist Bethany Young
Hold, PhD, is seeking to prove with a
soon-to-be-published study of young
American women. "Across the board,
women are uncomfortable talking to
their male partners about sex-whether
they're rich, poor, white or black," she
observes. Hold held focus groups to
gauge women's interest in
microbicides. Their responses were
encouraging and even produced sexy
packaging ideas, like a sleek gel (strawberry
flavored preferred) contained in
a lipstick-like case--the must-have
purse item of the coming decade.
For now, all eyes are on the holy
grail of FDA approval, which could
take another five years. But the war
chest for microbicide development remains
disturbingly light, with money
coming in piecemeal from the government,
academic grants, private foundations
and small biotech firms. According
to the Washington, DC-based
Global Campaign for Microbicides, an
Organization that raises public
Awareness and political and financial
support, only 1 percent of the federal AIDS research
budget, $35 million, is currently allocated
to microbicide research.
For veteran activists such as Anna
Forbes, the Global campaign's field
organizer, this is a frustrating state-ofaffairs.
"When we treat microbicides
like the ill-fated, red-haired stepchild,
we're just cutting off our nose to spite
our face," she says. "This could be
revolutionary."
If microbidides are going to take
hold, there needs to be a major public
education push. According to the Kaiser
Family Foundation, only 2 percent
of Americans have even heard of
microbicides.
A stronger show of political force
will also be necessary, which is why
people like policy officer Lara Stemple
are working on campaigns like the
California Microbicide Initiative
(CaMi) in Los Angeles. CaMI and
other groups have secured the sponsorship
of eight senators and 38 house
representatives for the Microbicide
Development Act, which would appropriate
money for a new microbicide
program at the National Institutes of
Health. Given the unpredictable AIDS
climate under the Bush administration-
with abstinence dominating the
federal HIV education agenda and a
paltry $200 million committed to the
UN global AIDS fund--even Forbes
concedes that the chance of passage is
slim. But just introducing the act
Only
1 percent of the federal AIDS research budget--$35 million--
is currently allocated to microbicide research
will generate
legislative awareness
and serve as a starting point for creative
funding strategies. "Global AIDS
is a hot issue on Capital Hill," she says,
"And if we can position microbicides
as part of the issue, then it has a much
better chance of making it."
With the profit sector playing possum
until the proof comes in, what's
urgently needed is funding from public
and philanthropic sources. "We're
looking for our Mrs. McCormick,"
Stemple says, invoking the wealthy
widow who, with reproductive- rights
activist Margeret Sanger, unsuccessfully
lobbied the pharmaceutical industry
to develop a safe, effective oral
contraceptive. In 1951, Katherine Dexter
McCormick put her International
Harvester money where her mouth
was, hiring the scientists to produce
the research that ultimately led to the
birth-control pill.
Before then, liberating women's
sexuality from pregnancy might have
seemed like speaking over wires, flying
through the air or rocketing to the
moon-once quixotic, even foolish, then
suddenly, perhaps accidentally, attainable.
When a microbicide liberates
women's-and gay men's-sexuality
from HIV, it could finally put the
brakes on history's worst-ever publichealth
catastrophe. But in the absence
of sufficient dollars and awareness, the
revolution in the sheets will require
what is sometimes equally hard to
come by: movement in the streets. "It's
clear microbicides are needed, and that
they're imperative," Forbes says.
"Since we're not able to attract corporate
support, we have to make it happen
ourselves."
