The Push for a Cure
The Search for an HIV Cure Is Ramping Up. So, Just How Close Are We?
Ten years ago, it wasn't getting funded. Sure, there was lots of basic research into HIV -- how it mutates, where it hides, why it is so damn elusive and tricky. But funding aimed specifically at finding a cure -- a way to clear HIV completely from the body? It just wasn't happening.
Yet we know how badly a cure is needed. Most of the millions of people in the world who are living with the virus aren't getting treatment. And those who are on treatment know the downsides: a lifetime of drug-taking, side effects, the risk of long-term negative health consequences, not to mention the stigma still attached to being HIV positive.
The good news is that there's a relatively new concerted global push to search for a cure. For example, the International AIDS Society (IAS) convened a global scientific conference in 2013 to focus more attention and energy on cure research. "Towards an HIV cure: people focused, science driven" was the slogan for the IAS effort.
Late last year, Canada joined the international effort. Two Canadian teams were awarded $10.7 million from the Canadian Institutes for Health Research (CIHR) and the Canadian Foundation for AIDS Research (CANFAR). This will fund research over five years in key areas related to a basic understanding of the human immune system, how the virus persists and what might be done to stop it.
One of the teams, led by Montreal microbiologist Eric Cohen, will research a particular group of immune system cells, their role as reservoirs for HIV and (it is hoped) strategies to eliminate the virus from these reservoirs. The other team, led by fellow Montreal microbiologist Hugo Soudeyns, will be examining the medical profiles of Canadian children now on HIV treatment for clues about how these children might live well without lifelong treatment.
"This research is not about stabilizing HIV at a low level through treatment," emphasizes Marc Ouellette, scientific director of the CIHR's Institute of Infection and Immunity. "It is about getting rid of the virus completely, or at least controlling it without the need for daily treatment."
Community advocates -- people who are HIV positive and belong to the communities that will be directly impacted by the research -- sit alongside Ouellette as members of the CIHR HIV/AIDS Research Advisory Committee. The research underway will involve translating the knowledge into clinical and/or commercial applications, the committee decreed. Both research teams hope to hold community forums to share their findings.
Why all this excitement about a cure for HIV now? What's changed is that a body of scientific knowledge has accumulated that makes it possible to organize research for a cure, says Robert Reinhard, the community representative on the steering committee for Cohen's research team.
That body of knowledge includes the examples of very unusual experiences that a few HIV-positive people have had before and after stopping antiretroviral therapy (ART) and at least two documented cases of individuals who no longer take ART being effectively "cured" of HIV. One, known as "the Berlin patient," has had HIV eradicated from his body. And the other, often referred to as "the Mississippi baby," no longer requires treatment and has experienced no viral rebound so far, though very small amounts of HIV can still be detected in her body (this is known as a "functional cure").
These events are, in everyday language, game-changers. In scientific lingo, they're known as "proof of concept" that a cure is possible.
Visconti and Gene Therapy
In 2012, hopes for the development of a cure for HIV were raised by the implications of the Visconti Study. By searching several databases, a group of French researchers, led by Christine Rouzious, was able to find 14 individuals who had started ART very soon after contracting HIV (during primary infection) and then years later, for unknown reasons, stopped treatment. Despite stopping treatment, they had very low levels of HIV -- and the virus did not rebound. This raised the hope that a functional cure may be possible.
There have also been small-scale gene therapy trials. These studies usually involve modifying CD4 cells to knock out a co-receptor needed by HIV to infect these cells. After this modification, the cells are multiplied and then injected into people. So far the results from this mode of intervention have been modest. This therapy needs to be further refined and additional studies are required to demonstrate the safety and efficacy of such a strategy.
But the two most often-cited events that have given rise to this new hope are the cures of the two individuals.
Berlin and Mississippi
When the so-called "Berlin Patient," Timothy Brown, went for HIV monitoring tests in 2009, his doctors found no evidence of HIV. Brown had been HIV positive for several years when he developed leukemia. After two bone marrow transplants from a person with a rare form of genetic resistance to HIV, and after chemotherapy and radiation as well as treatment for graft-versus-host disease (when the grafted cells attack the tissues and organs of the graft recipient), the virus was no longer found in Brown's blood. Nor was it found in any of the reservoirs where HIV usually sits dormant, ready to rebound when treatment is ceased. In addition to being cured of his leukemia, Brown became the first person in the world to have HIV eradicated from his body.
Then, in late 2013, it was announced that "the Mississippi baby" may have been "functionally cured" when HIV did not rebound after her treatment stopped. This baby girl was born HIV positive to an HIV-positive mother. Treatment of the infant with ART began 30 hours after birth. About 18 months later, for unknown reasons, the mother stopped her child's HIV treatment. And the child has had no signs of HIV since then. (Her health and HIV status need to be followed closely for any resurgence of HIV.)
More recently, the case of another child who appears to be free of HIV was announced at this year's Conference on Retroviruses and Opportunistic Infections (CROI 2014), though this child is still taking ART. The HIV-positive mother had not taken drugs to prevent transmission, and DNA and RNA of HIV were detected in her infant's blood. Four hours after birth, the infant was treated with potent triple drug therapy, and nine months later no virus can be detected, researchers have reported.
But very clearly, none of these can be considered a recipe for curing HIV. Replicating Brown's medical treatment -- which was costly both financially and in terms of the huge toll it took on his health and well-being, not to mention being life-threatening -- is by no means a blueprint for the cure of millions of people already infected. And any move to deliberately withdraw treatment from children for the purposes of research would require extremely careful ethical scrutiny and medical attention. Nevertheless, the findings are hopeful.
CROI 2014: Mississippi Baby Update, and Other Possible Cases of Patients Functionally Cured of HIV (Video)
This article was provided by Canadian AIDS Treatment Information Exchange. It is a part of the publication The Positive Side. Visit CATIE's Web site to find out more about their activities, publications and services.
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