The good news is that the scientists
are finally seeing a light at the end of
the tunnel in the search for an actual cure for AIDS. The disease was first stabilized almost
fifteen years ago and as this report makes clear, that part of the battle is
now well managed and victims are recovering their immune systems.
What was missing was a clear
pathway to a final cure although protocols are been developed that would lead
to a persistent decline in the affected population. Long term, we are going to beat this monster.
Now the buzz is that it will be a
lot quicker.
Importantly, today no one needs
to die from AIDS in his prime.
Curiously a friend of mine became
a victim around fifteen years ago and has been on a death march with the
disease in one clinical shift after another yet is still alive today and is now
under less stress from the disease itself (if any) . He is seventy five years of age and had zero
expectation of ever living out his natural life for most of the past fifteen
years. I was well briefed on the advent
of the cocktail and its many variations and modifications that make it so
useful.
This article is a pretty complete
update on AIDS and is worth the effort.
The End of AIDS
Beyond the drug cocktail. Beyond a vaccine. Scientists are talking
about total cure.
by Jill Neimark
From the October
2011 issue; published online November 8, 2011
Scanning electron micrograph of HIV-1 budding (in green) from cultured
lymphocyte.
This image has been colored to highlight important features.
This image has been colored to highlight important features.
Centers for Disease Control and Prevention's Public Health Image Library
One June afternoon in 1992, a dancer named Matthew Sharp died eight
times. A siren shrilled as he repeatedly dropped to the street and let
strangers draw a chalk outline around his body. Then he stood up, took the
chalk, and each time wrote the name of his partner, Johnny Franklin, inside the
empty space—just like a cop at a crime scene.
After Franklin ’s
death, Sharp nearly became another victim when he came down with extrapulmonary
tuberculosis. “I felt I was knocking on death’s door,” he says. “So I quit my
ballet company, took the life insurance money Johnny left me, and moved to San
Francisco, which was ground zero for HIV,” the AIDS virus. “For the next 20
years I stayed alive by participating in clinical trials of new drugs before
they were released. I was aggressive about preventing opportunistic infections.
When I began to die of wasting syndrome, I joined a trial for human growth
hormone. I got an experimental thymus transplant. Combination therapy in 2008
finally brought my viral load down to undetectable.”
Still, there was the problem of Sharp’s T cells—the white blood cells,
or lymphocytes, that unleash a powerful immune response against pathogens like
HIV. For AIDS, the most critical of the T cells is CD4, which would normally
coordinate the body’s attack against the disease. But by a quirk of biology,
CD4 cells end up sequestering the virus, which ultimately decimates them. With
Sharp’s CD4 cells hovering at around 250 per cubic millimeter of blood—a normal
count is 500 to 1,500—he was prone to a host of opportunistic infections and
qualified for a diagnosis of full-blown AIDS. “I was always in the danger zone,
and every year I would come down with pneumonia,” Sharp says.
Then came an invitation to participate in a novel form of gene therapy,
one that could mark a first step toward a true cure for AIDS. The trial was run
by Jay Lalezari, director of Quest
Clinical Research in San
Francisco . Sharp agreed to join. His blood was drawn
and his CD4 cells were filtered out, frozen, and transported to a laboratory
where they were genetically altered to resist invasion by HIV. This was done by
deleting a receptor on the surface of the CD4 cell that HIV uses to get inside.
The reengineered CD4 cells were allowed to multiply in the lab and then
returned to Lalezari.
In September 2010 Sharp received a single infusion of 20 billion of his
genetically engineered immune cells. Within weeks his CD4 count doubled. “They
test me every month and my CD4 count hasn’t fallen below 400. I haven’t had the
usual bout of pneumonia since this treatment. I’d love to get a second
infusion,” Sharp says. “I’m 55 years old and feeling better than ever, and now
there’s a possibility I’ll actually see a full cure of HIV in my lifetime.”
“We can’t be complacent. It’s an active, untreated epidemic in other
parts of the world. It could change and come back to haunt us in a new form.”
Curing AIDS? Wiping out a pandemic that currently affects 33 million
adults and 2.5 million children worldwide and infects
7,000 new people every day? In the 30 years since scientists identified HIV
as the cause of AIDS, the virus has proved unbeatable—hiding in the very immune
cells that would kill it; reflexively and rapidly mutating; mysteriously
persisting in the gut, kidneys, liver, and brain; subverting every vaccine (the
best one so far has given only 30 percent protection); and roaring back to life
almost the moment drugs are stopped. It has been years since anyone dared
whisper the word cure at all.
But they are daring again with growing confidence, buoyed by new
insights and technologies to fight a foe that Jay Levy, codiscoverer of HIV,
compares to a “biological Trojan horse” and Jay Lalezari calls “a cellular
bioterrorist that kills your first responders first.” Tapping into medical
advances from gene therapy to stem cells, researchers are launching powerful
counterstrikes against the virus. The National
Institutes of Health (NIH) will invest $70 million over the next five
years to support three multi-institution research efforts aimed at finding a
cure. And the independent International
AIDS Society, known for its conferences, has assembled a working group of
world experts to spearhead a global strategy for the cure.
The latest turn seems as remarkable as the one patients celebrated in
1996, when David Ho of Rockefeller University in New York presented his
research on a combination
drug therapy, a treatment cocktail that rendered the virus undetectable in
blood. That work turned AIDS from a certain killer into a chronic disease
almost overnight. “I remember witnessing a miracle,” recalls Steven Deeks,
an expert in the pathogenesis of HIV at the University
of California , San Francisco (UCSF). “Literally within
weeks, people went from a death sentence to a promise of years of health.
People in hospices were sent home. And now there is a possibility we’ll have
another dramatic shift.” He cautions, however, that it took “15 years to
get from that first antiviral to truly effective, well-tolerated combination
therapy. I think in terms of a total cure, we’re just now starting another
15-year journey.”
Renewed hope that we can defeat HIV is especially remarkable because of
all we know about this outrageously complex and wily retrovirus—so called
because it replicates by reversing the molecular process that most other
viruses use. In most cases, viruses start with DNA as their primary genetic
material and make RNA templates of themselves. Retroviruses, on the other
hand, start with RNA and make DNA templates, using an enzyme called reverse
transcriptase; the resulting DNA then exploits human cellular machinery to
create more copies of the virus. HIV’s favorite target is the CD4 T cell, which
orchestrates our entire immune response against the disease. The virus worms
its way into the CD4 cell via several receptors—or molecular doorways—on the
cell’s surface, including a crucial one called CCR5. Then it plunders
that cell’s supply of reverse transcriptase.
If the CD4 cell is quiescent, the HIV rests too. But if the CD4 cell
is
activated by anything, from stress to the common cold, the HIV inside becomes
active as well, generating DNA templates that integrate into the human genome
within the CD4 cell. Instead of killing HIV, as it would do with other viruses,
the CD4 cell makes more copies of HIV, which then leave to invade
other CD4 cells, ad infinitum, until an irreversible, lethal cascade has been
unleashed.
The CD4 cycle alone would be enough to kill a person, but HIV also
enters other cells, integrating into their genomes as well. The latent virus
lurks, seemingly dormant but actually awaiting its cue: Anything that stirs the
immune system—stress at work, food poisoning, grief—can jolt HIV combatants to
action too. Some scientists suspect that this latent reservoir causes the
long-term inflammation often experienced by people living with HIV, even when
they are on the drug cocktail that otherwise controls the disease. Over the
years, latent HIV might wreak silent havoc, making the need for a true cure all
the more pressing as time goes on.
Recent studies clarify the limitations of Ho’s combination drug
approach. A multicountry study published
in The Lancet in 2008 found that someone starting HIV
treatment at age 20 could expect to live to 49, a reduction of 27 years
compared with those without the disease. Then there is what doctors call neuroAIDS.
Even with antiretroviral treatment, between 40 and 60 percent of HIV-infected
individuals develop mild neurological dysfunction; 1 to 5 percent develop
dementia. A recent study suggests this syndrome results from the way HIV
injures astrocytes, the most common type of cell in the brain. In people
with AIDS, about 5 percent of astrocytes are infected; some scientists
speculate that these cells, in turn, spew out toxins that ultimately kill
uninfected astrocytes nearby.
Furthermore, today’s drug therapies are aimed specifically
at the
current strains of HIV, but the virus will probably mutate, as every virus
eventually does. “We can’t be complacent,” says Jay Levy, now director of the
Laboratory for Tumor and AIDS Virus Research at UCSF. “It’s an active,
untreated epidemic in other parts of the world. It could change and come back
to haunt us in a new form.”
In the accelerating search for a cure for AIDS, medical researchers are
actively pursuing three broad approaches. The first approach is gene
therapy, in which a patient’s cells are genetically engineered to be
invulnerable to HIV; this naturally
occurring resistance already exists in 1 percent of Caucasians worldwide. The
second approach involves latency activators, molecules that lure the virus out
of its hiding places and into the open, where the body’s immune cells and
targeted drugs are able to find and destroy it once and for all. Finally,
scientists are intensely studying the immune systems of a unique group of
people known as elite suppressors, who remain healthy after HIV infection,
controlling the virus for decades on end.
Impressive advances in the lab and in patient trials make all three
strategies look promising, but in the end there might not be a single cure. As
with today’s drug cocktail, the best solution might be a combination of two or
perhaps all three. And even the concept of “cure” may need adjusting. Since it
would be staggeringly difficult to test every single cell in the body for the
presence of HIV, a patient will be considered cured if there is no evidence of
the disease for a certain length of time after the completion of treatment. For
millions of patients, that would be a life-transforming and life-affirming
event.
“It sounds like science fiction, I know, as if I just told you people
landed here from Mars,” Tebas says. “That’s how far the technology has
evolved.”
Anyone lucky enough to resist infection with HIV altogether likely
lacks the CCR5 receptor on the surface of his CD4 cells. The existence of this
natural protective mutation was first
reported inNature in 1996. When Gero Hütter, today a specialist in
blood cancers at the Institute of Transfusion Medicine and Immunology in Mannheim , Germany ,
read about it, he was transfixed. “I thought, wow, this could be a way to treat
HIV.”
But conferring resistance on someone not born that way is a tall order.
It requires redrawing the immune system by knocking out the existing cells and
administering HIV-
resistant stem cells that can establish a new immune system.
Given the effectiveness of the drug cocktail, Hütter would not have considered
such a risky procedure for AIDS alone. But if he were performing a stem cell
transplant for a cancer patient who also happened to have AIDS, he reasoned,
then why not use stem cells with the CCR5 deletion? “And then I forgot about
it,” he says, “because I never saw a patient I could try it on—until Timothy
Ray Brown showed up.”
Brown is the only person alive today who has been cured of HIV. He is,
in the words of Gerhard Bauer, a stem cell researcher at the University of California ,
Davis , “the
world’s first natural gene therapy experiment for HIV.” He came to Hütter—who
was then at the Charité, a university hospital in Berlin —in 2006 with leukemia and an HIV
infection that was well controlled with combination antiretroviral therapy.
After cancer chemotherapy failed, Brown needed a stem cell transplant for his
leukemia. The doctors’ plan was to kill off Brown’s cancer-producing bone
marrow cells with intensive chemotherapy and replace them with stem cells from
the bone marrow of a healthy donor. Hütter looked through multiple donor
registries and tested the blood of more than 200 candidates for someone born
with the CCR5 mutation. Luck was on Brown’s side: A matching donor had the
deletion. Brown underwent his stem cell transplant and stopped taking his
antiretroviral drugs. For 60 days afterward, there were still signs of viral
DNA in his genome, but then it seemed to vanish. “The clearance of the HIV
reservoir was quite rapid,” Hütter says, sounding as astonished in 2011 as he
was back in 2007.
One year later Brown’s cancer returned, and he was given another stem
cell transplant from the same donor. Today he is free
of both cancer and HIV. Hütter speculates that Brown was helped to a total
cure by what is known as the host-
versus-graft reaction: New stem cells and
all their progeny see the old immune cells as “other” and kill them off. When
that happens, all the latent reservoirs of HIV that are permanently integrated
into the genomes of those cells can be eliminated as well. Brown is now being
studied in San Francisco
by Jay Levy and his colleagues. “The fact that you can find a person who had
AIDS and who now seems to have eradicated the virus is remarkable,” Levy says.
The treatment that cured Brown of his HIV and cancer has some
devastating potential downsides, however. For one, transplanted donor cells can
be rejected just like a donor heart, putting the patient at risk of disease and
often requiring powerful immune suppressants, with all the attendant side
effects and risks. With the current AIDS drug cocktail so effective, such dangers
would be unacceptable unless, as with Brown, the patient needs bone marrow
therapy anyway.
Building on Brown’s amazing recovery but hoping to avoid the
pitfalls, AIDS researchers are devising treatments based on the patient’s own
tissue, which would not be subject to rejection like donor cells. One of the
most promising approaches uses a new type of genetic scissors known as zinc finger nucleases,
developed by California-based Sangamo Biosciences. These finger-shaped
proteins form when specific amino acids (protein building blocks) bind to a
charged zinc atom. They can be engineered to go into cells and snip any gene a
researcher wishes to target (including the gene for the T-cell receptor CCR5).
The damaged cells automatically set about repairing the cut, yet 25 percent of
the time that effort fails, and the deleted gene is never restored. Such cells
can be separated out, creating a pool of HIV-resistant cells lacking CCR5.
These lab-engineered cells can then be amplified and grown out a hundredfold or
more before being infused back in. They are safer than cells transplanted from
a donor because risk of rejection is gone.
The first human trials testing genetically engineered cells missing the
CCR5 receptor, begun in 2009, have been small but impressive. At Quest Clinical
Research, Lalezari enrolled nine men on the cocktail with persistently low CD4
counts who were HIV positive for 20 years or more. The genetically engineered
cells survived after infusion, and CD4 counts went up in five of six patients
he has reported on, including Matt Sharp. “The ratio of two types of immune
cells, CD4 and CD8, which are often abnormally reversed in HIV, normalized, and
the HIV-resistant cells even migrated to the gut mucosa, an important site for
the virus,” Lalezari says. “The results were as good as I could possibly have
hoped for.” Though his approach is distinctly different from a donor stem cell
transplant like Timothy Brown’s—in which the entire immune system is
replaced—it is a promising start, with potentially significant clinical benefit
and far less risk.
A similar
trial launched in 2009 by pathologist Carl June and internist Pablo
Tebas at the University
of Pennsylvania has shown
equal promise. Here, six patients suspended combination antiretroviral therapy
for 12 weeks after infusion with altered CD4 cells, so scientists could monitor
viral load and the power of the altered immune cells to survive and thrive in
the presence of active HIV. At present, two of the patients have been fully
studied. In one patient, the virus took 10 weeks to rebound instead of
the
usual two to four weeks. In the other patient, the virus was still undetectable
12 weeks out. The next step is to increase the percentage of genetically
engineered cells, either by increasing the amount of cells in the infusion, by
giving more than one infusion, or by administering chemotherapy to lower the
number of untreated CD4 cells in the body before infusion begins. Other
researchers plan to try this approach on patients who recently received a
diagnosis of HIV and are not yet on antiretroviral therapy. “It sounds like
science fiction, I know, as if I just told you people landed here from Mars,”
Tebas says. “That’s how far the technology has evolved.”
The most viable form of this treatment might be to target progenitor
cells giving rise to CD4 cells and the rest of the immune system—stem cells
themselves. If some of those cells could be removed from a person with AIDS,
genetically engineered to be resistant, and then returned to the patient, they
might spawn an immune system that is completely resistant to the disease. The
virus could actually help, since it would continue infecting and killing
unchanged, vulnerable cells—decimating its own resources in the process.
A stem cell
transplant like this has already been accomplished in mice by
virologist Paula Cannon of
the University of
Southern California .
Cannon used a special strain of mouse that lacks a functioning immune system
and so can be given human immune cells without rejecting them. Mice were
infused with human stem cells, half of them genetically engineered so that the
CCR5 receptor was gone. After 8 to 12 weeks, the modified cells had increased
in number, effectively resisting infection with—and controlling replication
of—HIV.
“These mice are a real breakthrough for HIV research,” Cannon says.
“But now we need to find the sweet spot, the Goldilocks spot, where we can
alter enough stem cells to allow someone to live with HIV.
For the ultimate cure, we might have to purge HIV infection from its
silent
reservoirs, routing it out so it can never
recrudesce and cause damage
again.
Ultimately an anti-AIDS stem cell transplant might look like this: You
would have your stem cells withdrawn and genetically altered to resist HIV.
Simultaneously, you would get a mild form of chemotherapy to wipe out some of
your remaining vulnerable stem cells. Then you would get an injection of the
new stem cells. They would proliferate rapidly and create a resistant immune
system. This immune system, especially the CD4 T cells, would have an advantage
because HIV could never invade or kill them, and over time, they would become
dominant.
Some researchers are optimistic that stem cell therapies might be able
to deliver what researchers call a functional cure: Patients would achieve a
state of remission in which the viral load was less than 50 copies of HIV per
milliliter of blood, undetectable on standard tests, and they would no longer
require medication. “This therapy isn’t about eliminating every last HIV from
the body. It’s about giving the body the tools to stay well when the reservoir
wakes up,” Cannon states. “If people can have this treatment, not have to take
HIV drugs, not have detectable levels of the virus, and have a fully
functioning, happy immune system, isn’t that good enough?”
Not for David Margolis,
an AIDS researcher at the University
of North Carolina at Chapel
Hill . When the virus lurks in latent reservoirs in the body, he
says, there are consequences for patients’ health. “You’re not going to cure
HIV this way. It’s a giant technological problem as difficult as inventing a
warp drive to travel to other stars. Unless you go in and kill all the stem
cells that make CCR5, there will always be cells that the virus can grow in.
You may lower the load, you may even prevent disease progression and eliminate
need for antiretrovirals, but you will still have chronic immune activation and
the problems caused by that.”
For the ultimate cure, doctors might have to purge HIV from its silent
reservoirs, routing it out so it can never recrudesce and cause damage again.
Margolis and collaborators hope to do just that through a “sterilizing cure”
that spurs HIV to start replicating within its hiding spots; when the virus is
actively dividing, antiretrovirals can get in and do their job.
Initial attempts to lure HIV out of hiding did not fare well. An early
trial conducted in the mid-1990s in the Netherlands used inflammatory
antibodies to fire up patients’ immune systems in hopes of activating the
dormant CD4 cells where HIV was stowed away. The antibodies did in fact
activate the CD4 cells but eventually killed them as well, depleting the body’s
best weapon against HIV. “The early studies failed miserably and had toxic side
effects,” says virologist Warner Greene of
UCSF. “Ultimately we need to find molecules that activate the virus without
activating the T cells or other viruses, and it’s not a trivial task.”
Some molecules are already showing promise. For example, an enzyme
called histone
deactylase (HDAC) keeps HIV turned off, a crucial part of the virus’s
strategy of hiding in the T cells to avoid the body’s defenses. But in 2000,
Margolis and his group discovered that they could use HDAC inhibitors—drugs
already approved for stabilizing mood and preventing seizures—to reverse the
effect and draw out the virus. First, the team tried a common and relatively
weak HDAC inhibitor called valproic acid to bring latent HIV to life. “It was
not the best drug, not the most specific or potent, but it was already in
clinical use, and people were taking it every day,” says Margolis, who
published his initial results in The Lancet in 2005. It worked to a
degree, reducing latent HIV load without activating T cells in about half the
patients, though even in that group the effect plateaued or weakened over time.
He is now focusing on a far more potent HDAC inhibitor, a relatively untested
drug called vorinostat that is currently used to treat a few rare types of
cancer. Finally, an immune molecule called interleukin-7 seems to flush out
viruses from CD4 cells. Studies have shown it is well tolerated in HIV-positive
patients on antiretroviral therapy, and several clinical trials are under way.
The hitch: Perfecting this kind of treatment could require a
complicated and possibly dangerous new drug cocktail. HDAC inhibitors may
activate viruses other than HIV, unleashing a plague from within.
AlteRNAtively, they could increase the risk of cancer by changing the way in
which cells transmit genetic instructions from DNA to cellular proteins.
“Whether these approaches will work alone or require additional combination
therapies is a question that we hope to be able to answer in the next few
years,” Margolis says. “This is not going to be a single-shot, zero-sum game.”
The puzzle pieces should come together once we understand a special
group of patients called elite suppressors, the one-in-300 HIV-positive adults
with turbocharged immune systems capable of hunting and killing HIV. Timothy
Ray Brown and others missing the CCR5 receptor beat HIV because their cells do
not allow the virus to get in. Elite suppressors stay healthy because they
pummel the virus and hold it at bay.
In June 1992 Loreen
Willenberg, then a 38-year-old landscape designer, dreamed that she had
been infected with HIV. “I suspected my former fiancé of risky behavior, so I
went to get tested,” she explains. That test was equivocal; with the dream
still haunting her, she got tested again two weeks later. “This time I was
positive,” she says.
That September Willenberg saw an HIV specialist and her CD4 count came
back astoundingly high—over 1,800. “My doctor said, ‘Look, this is very
extraordinary, let’s just keep tabs on you.’ After three years of undetectable
viral load and a high CD4 count, he said, ‘Loreen, I think you’re a member of a
special group that’s being studied at the NIH now. They get infected and stay
infected, but they don’t get sick.’ ” Twenty years after getting diagnosed,
Willenberg is still healthy and has participated in several long-term studies
aimed at decoding why her body has been able to prevail over AIDS.
“I came out about a year before the first AIDS cases were recorded. I had
one brief, glorious moment before the world came crashing down. Now we’re
talking about a cure.”
At first scientists speculated that patients like Willenberg were
infected with a weaker version of HIV. Joel Blankson of the Johns Hopkins
School of Medicine found otherwise.
“They have a fully pathogenic virus,” he says, citing his study of a monogamous
married couple infected with the same strain of HIV. The husband, a former drug
user, contracted the virus 20 years ago. Seven years later, the wife was
diagnosed. “He’s on triple antiretroviral therapy, and she is an elite
suppressor who never got sick.”
Only now are scientists beginning to understand the biochemistry that
makes this possible. One factor: differences in surveillance proteins
called human
leukocyte antigens (HLAs) embedded in our cells. These molecules
function by shuttling broken-down proteins called peptides from inside the cell
to the surface, where other immune cells inspect them to see whether they are
invaders. HLAs come in hundreds of forms, but elite suppressors tend to have
two specific types, HLA-B*27 and HLA-B*57. A study published last year by the
Ragon Institute (formed to facilitate collaboration among vaccine researchers
at Massachusetts General
Hospital , Harvard, and
MIT) suggests that those antigens may help educate CD8 immune cells to make
them more potent against HIV, as well as hepatitis C. All CD8 immune cells—like
the CD4 cells that harbor HIV—mature in the thymus (an organ devoted to the
production of T cells) before taking up active duty in the body; while there,
HLAs expose the CD8 cells to a variety of peptides, both human and foreign.
Some HLAs—particularly HLA-B*57—tend to bind to a much higher proportion of
foreign particles; more HLA-B*57 means that the CD8 cells will be exposed to a
broader range of foreign peptides, improving their ability to identify and
terminate invaders, including, presumably, HIV.
Yet the unique HLA pattern doesn’t explain it all, according to Bruce
Walker, one of the study’s authors. Walker ’s
colleagues tested the genes of 1,110 elite suppressors and 620 HIV-infected
controls. They found that while elite suppressors often have the rare set of
genes that code for HLA-B, those genes are “neither necessary nor sufficient”
for controlling the virus. In other words, some elite suppressors lack the
HLA-B genes and some non-suppressors have them. So the search goes on.
Recently, for instance, the team found a group of elite suppressors with
elevated levels of p21, a cancer-fighting protein that disrupts key aspects of
the HIV life cycle in the lab.
While it’s too early to grasp all the factors involved, elite suppressors
should help us finesse the cure and eradicate AIDS for good. Two decades ago,
researchers imagined that a vaccine would end AIDS. Their approach proved
unfeasible, but the goal is now in reach. “This has been an amazing year,” says
Jeff Sheehy, communications director at the UCSF AIDS Research Institute and a
board member of the AIDS Policy Project, also positive for HIV. “I came out
about a year before the first AIDS cases were recorded. I had one brief,
glorious moment before the world came crashing down, and this has defined my
whole life. Now we’re talking about a cure.”
WHY SOME PEOPLE ARE IMPERVIOUS TO AIDS
AXS Studio INC.
Approximately 1 percent of Caucasians lack a protein called CCR5 on
their CD4 T cells—the white blood cells that normally kill invaders but that
harbor HIV. CCR5 is a molecular doorway that lets the virus in. Since HIV
depends on CCR5 to slip inside the CD4 cells, people with the receptor are
prone to develop AIDS. Those without the CCR5 portal generally do not take HIV
into their CD4 cells and have natural resistance to AIDS. Gene therapy could
impart this kind of resistance to others.
DRUGS FOR THE HIV-FREE
University of North Carolina immunologist Myron
Cohen was amazed to hear thunderous cheers from the audience of
scientists and clinicians at the sixth International AIDS Society Conference on
HIV in Rome last July. He had just
presented results of a landmark trial of 1,763 heterosexual couples from nine
countries in which one partner was infected with HIV and the other was
virus-free. Early use of antiretroviral therapy for HIV, Cohen found, slashed
the risk of transmitting the virus by 96 percent. In other words, drugs now
used to treat AIDS could also prevent its transmission, winding down the
epidemic if enough people begin therapy early.
The study randomly assigned couples to one of two groups. In one, the
infected partner began drug therapy immediately. In the other, infected
partners deferred treatment until their CD4 T cells (the immune cells the virus
targets) fell to a perilous count below 250, or until they suffered an
AIDS-related illness. Couples in both groups received HIV primary care,
counseling, and condoms. After announcing their preliminary findings, Cohen and
his colleagues offered treatment to all of the study participants and will
continue to monitor them to see how the effect holds up over time. They are
also planning a second study on men who have sex with men.
In a related study conducted in Kenya
and Uganda , University of Washington scientists reported a
profound reduction of transmission when a noninfected partner was treated
instead of the infected partner. Uninfected partners
who took a drug called
tenofovir had a 62 percent drop in HIV infection; those who took a combination
of tenofovir and another drug, Truvada, saw a 73 percent decline. With the
Centers for Disease Control developing guidelines that would
allow an
uninfected person to take Truvada, the era of AIDS prophylaxis is about to
begin.
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