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October / November 2010
From Mice Into Men
by Regan Hofmann with Tim Horn
The gap between groundbreaking scientific discoveries and a game-changing cure has never been greater. And yet, researchers say we could be closer to a cure than many have dared believe. To close that gap, and increase the chances we’ll see the end of AIDS in our lifetimes, we need more advocacy, a lot more money and the courage to get as many viable options out of mice and into humans. You in?
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Cure. It’s a word few have been willing to pair with AIDS since we thought we had the virus kicked in ’96. For nearly 15 years, talk of a cure has been verboten. Those who have dared utter it (including on the pages of this magazine) were dismissed as dreamers. Since the late 1990s, research, advocacy and funding around HIV/AIDS have focused almost exclusively on prevention and treatment. And yet, it has become clear that we can neither treat nor prevent our way out of the pandemic. The ethical, logistical, sociological and financial barriers to trying to end AIDS with pills and awareness campaigns are proving too great.
The cost of providing antiretrovirals (ARVs) indefinitely to all people globally who will need drugs to survive is staggering; it’s estimated to be in the tens of trillions of dollars, not accounting for inflation, an ever-growing caseload and future drug prices. Not even the combined coffers of all the global health funds, the biggest health care foundations and the richest nations and individuals around the world are prepared to foot that bill. (The price tag also poses the question: Even if we could raise the tens of trillions of dollars, why would we spend that much money on treating HIV when it could take far less to find a cure?)
The biggest, pinkest elephant in the room is that since no one, especially in this global economy, is likely to spend the money required to keep the 33.4 million people UNAIDS estimates to be living with HIV today alive—tens of millions of men, women and children are going to die of AIDS in the near future. Unless we find the cure.
So where is the bloody thing? There has been talk of conspiracy. Woefully inadequate funding for cure research. Risk-adverse venture capital investors. Abandoned biotech babies. And precious little advocacy. While the HIV community was focusing on everything from improving treatment options to funding lifesaving programs like the Ryan White CARE Act and the AIDS Drug Assistance Program and developing a National HIV/AIDS Strategy, it seems we forgot to demand the one solution that could eliminate the need for all the rest: the Big C.
But though the subject of an AIDS cure has long been unmentionable, that doesn’t mean it isn’t possible, or even probable. In fact, surprisingly, given the lack of adequate funding, AIDS cure research has produced some really exciting breakthroughs. In an interview with POZ at the XVIII International AIDS Conference (IAC) this past July in Vienna, Kevin Frost, the CEO of the Foundation for AIDS Research (amfAR), said, “The research around a cure has been going very well. It’s one of the great, untold stories of AIDS today. Much of [AIDS cure] research is headed in a very positive direction, and there’s genuine enthusiasm in the scientific community about the possibilities of how we get there. We’re not going to get there tomorrow or next week, but there’s a growing sense of excitement about our progress that, for the first time, shines a light on the pathway to [the cure].”
Optimism for a cure within the scientific community is at an all-time high. The challenge is getting the myriad possible options beyond a laboratory setting—and into human trials. In today’s medical research there is an gap (known as “the valley of death”) between exciting new scientific discoveries and the dollars, leadership and advocacy needed to turn those ideas into medicine we can use. Within the world of AIDS research, a prime example is the case of Paula Cannon, PhD, who works at the University of Southern California. She is using zinc-finger nucleases (ZFNs)—synthetic DNA-binding proteins developed by Sangamo BioSciences—to genetically alter stem cells capable of producing CD4 cells that don’t have CCR5 receptors. The big deal? HIV can’t bond with, and infect, CD4 cells that don’t have these receptors. The procedure worked well in mice that were specially bred to be born without immune systems so that they could receive transplants with ZFN-modified stem cells and then be exposed to HIV. Cannon, Sangamo and John Zaia, MD, are ready to conduct a similar experiment in HIV-positive patients with lymphoma who undergo chemotherapy. People living with HIV are willing to be subjects in Cannon’s trial. Cannon and her colleagues have been given an initial grant of $14.5 million from the State of California. But the rest of the money needed to turn her theory into practice is not looming on the horizon. For now, her hope for a cure remains trapped in the bodies of her mice.
In 1996, scientists thought they’d hit the cure jackpot with the debut of a new class of drugs called protease inhibitors (PIs) that made it possible to construct potent combinations of drugs equipped to attack HIV at multiple stages of its lifecycle. Protease-based combination therapy profoundly reduced the amount of HIV in the body. Many researchers believed PIs could permanently snuff out the virus after just a few short years of treatment. The hype increased when David Ho, MD, famously suggested, as did a December 1996 cover of Newsweek, that combination therapy could prove to be the cure. But the bubble of hope burst with the discovery that even people with undetectable viral loads harbor a small population of immune system cells that are literally “sleeping with the enemy.” These cells, a group of 1 million or so “resting” memory CD4 cells—semi-retired holdouts from earlier immune system battles with microorganisms—are infected with HIV and go largely untreated by today’s crop of antiretroviral drugs. (ARVs only protect uninfected cells or keep active CD4 cells from producing new HIV.) Thanks to these cells, when most people stopped taking their multi-drug cocktails, the virus bounced back with a vengeance. Because it can take decades for the infected memory cells to either wake from their slumber (and allow HIV meds to do what they do best) or die a natural death, eradication via ARVs alone would require more than 60 years of uninterrupted therapy. The fact that HIV was capable of hiding in this manner—“latency” in medical terminology—dashed the hope that combination therapy could eradicate HIV from the body.
When protease-based combination therapy proved not to be the cure, scientists and funders turned primarily to the development of a vaccine, the refinement of new treatment options and improved prevention tools. These areas offered greater hope for glory—and greenbacks. As a result, today we have many highly effective and better-tolerated ARVs. We have made important discoveries on the preventive and therapeutic vaccine fronts. And we are closer than before to developing effective microbicides (drug-infused gels that can be applied vaginally and/or anally and serve as a barrier to HIV infection). Meanwhile, we have spent relatively precious little money and effort on cure research.
The National Institutes of Health (NIH) reports that it has spent $45 billion on all forms of AIDS research in the past 28 years. (In 2009 alone, the United States spent $20 billion on AIDS prevention and treatment for people stateside and abroad.) According to a report released recently by The AIDS Policy Project (APP), the NIH spent a mere 3 percent of overall AIDS spending (or $41 million of $1.5 billion) on AIDS cure
research in 2009. The APP is calling the NIH to increase AIDS cure research funding five-fold—to $240 million—in 2011 and to $600 million a year within five years. Currently, the NIH spends nine times as much looking for a vaccine as it does looking for a cure. But the APP does not suggest the NIH “borrow from Paul to pay Peter” but rather that it ups the ante across the board; the APP suggests Congress should increase NIH funding (as President Obama promised during his campaign) by 20 percent, effective next year.
A vaccine that is therapeutic (meaning it could help people’s immune systems keep HIV undetectable without ARVs) could constitute a “functional cure.” But there is a strong case to be made that recent knowledge on other research fronts begs as much devotion as our search for a viable vaccine. For too long, too many people have given up on the cure. The APP’s report claims that few outside the research community are aware of what’s going on with AIDS cure research, “not members of the general public, nor most health reporters. Nor the United States Congress, which decides how much to fund the National Institutes of Health. Not even most AIDS activists, who assume the cure is decades out of reach. And, most importantly, not people with AIDS themselves, millions of whose lives are at stake.”
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comments 1 - 11 (of 11 total)
Mark, Toronto, 2012-03-10 12:43:47
After 22 years I have yet to see any evidence that Pharma's could block a cure even if they wanted to. The fact remains HIV is complex and wily, and our science is just not quite there yet. But its easier to blame the invisible man behind the curtain.
Berry, Amsterdam, 2011-05-09 06:40:42
I loved this articale. I am some one who has probably been infected with HIV(have to wait 2 more months on the outcome) Now I know there realy is hope of finding a cure
vc, , 2011-03-21 15:43:49
I'm sure as hell in times of wikileaks the big pharmas couldn't hide a cure, but i can't answer in terms of pharmas slowing down the process. i'm also sure about that pharmas will have an occupation.
papilword, atlanta, 2011-03-11 16:10:57
such an interesting article. but should the next article/poz cover be about conspiracy theories and if they're true or not? for every person who gives positive information about a cure, there is another who says pharmacies are in control. is this true? should we believe this when so many are suffering. it scares me to think that a cure would be witheld because of pharma or gov. is making money. can anyone help me with these questions?
ethanwilson, Nashville, 2011-03-02 01:02:20
I am a fan of Ms. Hofmann's writing. And it made my heart sing, to read this brilliant article.Are we going to stand up and fight for a cure, when we are so close? The answer is yes! But we need to do it now,when the berlin patient has shown us the way. More and more, i hear the commom conspiracy theories...i ask...what good is this doing for those who are positive and who are sick? No. We need to direct our energy and commom sense toward the cure now. Please let's take a stand.
James, Winnipeg, 2011-02-22 13:29:22
I truly agree with Harsha. I believe after 20 years of intense research we know enough about HIV. We know plenty. I think a cure could be developed quickly, but these meds are a great safety net for many drug companies. I think it's a crime we don't have a cure yet. We need to stand up and start to stir the porriage.
kenny, Fort Collins, 2010-12-08 14:16:15
The Fact of the matter is that many people will loose their jobs if thier is a cure and that would hurt a lot of people and their neg families Do they really care about the impact on positive people and their families. I think not If they could live the life that people like myself who is raising two children and taking all the meds just to stay healthy they might chage thier minds.But That woin't happen and if their is a cure i would bet my life they would only give it to people who could pay.
Harsha, , 2010-10-27 15:50:26
VEry true, Who knows what the hell s happening on the name of RESEARCH AND CURE OF HIV AND AIDS, I am sure there is cure but the multinational companies wont let it out as they want to earn by selling their meds.... thats all,, or else is there not 1 genius in this world who can find cure to this desease....
Karen W, Sanford, Florida, 2010-10-12 13:01:45
You GO Waldon A.!!! We need patients like you to stand up and show what you want - not bitch about what you do or do not do, have or do not have. I want allof my patients to know they still have LIFE and make something of it. My clinic can;t even get consumer advisory boards to activate. We need people like you - God Bless. Karen W Florida
scott sproat, pacheco, california, 2010-10-09 18:18:07
our government has had a cure for AIDS but they want to weed out gay people first. gay men would have never got infected had it not been for heterosexuals who actually started this epidemic. still today-most heteros NEVER use a damn condom. they continue to blame us gay men for all of it. its a bunch of BS.
Waldon, dc, 2010-10-08 06:06:32
comments 1 - 11 (of 11 total)
Being a rapid progresser, currently having a spat of good health, I love it when people start talking cure. Most of diseases have walks for the cure. You almost never hear that word when it comes to AIDS. I just won the courage award in the dc aidswalk this year, and am willing to do anything I can to promote funding for a cure!!!! I plan to run a marathon every year, when I can afford it, until there is a cure. My name is Waldon ADAMS,and I have a AIDS diagnosis!! I run for AIDS cures!!