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Opinion Pieces

Jul24

The push for a cure

Thursday, 24 July 2014 Written by // CATIE - HIV and Hep C Info Resource Categories // Research, Health, Living with HIV, Opinion Pieces, CATIE - HIV and Hep C Info Resource

From CATIE’s The Positive Side “The search for an HIV cure is ramping up. So, just how close are we? Ann Silversides reports.”

The push for a cure

This article previously appeared in The Positive Side, a publication of CATIE, here 

Une version française est disponible ici. 

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.Cure graphic

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 now?

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.

A note of caution

Sean Hosein, CATIE’s science and medicine editor, warns that “it’s still early days—these are small steps being taken toward a cure.” Scientific research does not always proceed in a straightforward manner. For example, until the advent of effective ART in ’96, hopes for effective treatment were regularly raised and dashed. These days, premature news about HIV cure research risks creating a similar emotional rollercoaster for people living with HIV. Overhyping an HIV cure also risks diverting attention away from efforts to make those treatment and prevention strategies that we already have and we know work readily available.

“It’s a very big deal” that two Canadian teams have been funded to pursue this type of HIV research, says Robert Reinhard. He warns that a cure is not on the immediate horizon and that continued research into other important areas—such as new treatments, hepatitis co-infections, vaccine research—are no less important than cure research.

As encouraging as these examples are, “nobody knows why Timothy Brown or the baby were cured,” Reinhard stresses. “We have educated guesses and suspected answers, but nobody knows. We know a couple of things about what are not the reasons, because of the Boston patients.”

He’s referring to an attempt to replicate much of Brown’s treatment—bone marrow transplant and chemotherapy—in two people with HIV in Boston who had also developed lymphomas, cancers of the immune system. But the treatment did not have the same results: After HIV therapy was withdrawn, the virus rebounded in both individuals.

The Canadian niche

Canada has a distinguished history of HIV research, beginning with the development of the antiretroviral drug 3TC and later on with early attempts at cure research. Back in 2005, researchers across Canada attempted to cure HIV infection by adding the anti-seizure drug valproic acid to the regimens of some people who were taking ART. Unfortunately, that attempt did not result in a cure.

Because many studies are investigating the role of CD4 cells as viral reservoirs, Eric Cohen’s team is going in another direction—looking at myeloid cells, another type of immune system cell infected by HIV. These cells are found in many tissues, including the testes, brain and guts, where antiretroviral drugs do not penetrate well, explains Cohen, who has conducted research into HIV since 1986. Myeloid cells are more resistant to HIV after they are infected—the virus does not kill them as rapidly as it kills CD4 cells—so they also play a role in HIV reservoirs.

Cohen’s team brings together scientists and clinicians from six universities and research centres across the county. The team aims to identify and characterize the properties of these cells in animals and humans; determine the mechanics that govern HIV latency (when HIV-infected cells are “hiding” and not actively reproducing HIV but can be reactivated); develop strategies to eliminate HIV reservoirs; and, eventually, conduct clinical trials to test the effectiveness of strategies.

Soudeyns’ team, comprising researchers and doctors who care for HIV-positive children, will be studying the 243 Canadian infants and children who were born with HIV and are on ART. The effort, called the Canada Child Cohort study, was inspired in large part by the Mississippi baby reports. The team aims to discover if starting ART early can lead to a functional cure, a discovery that would mean “the standard practice for treating children can be changed,” Soudeyns notes.

Like Cohen’s team, these researchers will use several different tests to detect and measure HIV that may sit dormant in reservoirs. If no virus is detected, treatment interruption would be discussed—and any decision would be subject to rigorous ethical and informed consent guidelines.

Of the Canadian children being followed, only a handful started ART early—in the case of all these children, therapy was initiated within 72 hours of birth. Most of these children are now school aged.

In Canada few infants are born with HIV—since 2005, fewer than 10 a year, and in 2012, none. These cases are typically the result of the mother not knowing she was HIV positive and not having appropriate prenatal care. The risk of transmitting HIV to an infant is very low—less than 1 percent provided specific steps are taken. (During pregnancy, the mother takes ART to lower her viral load to less than 50 copies/ml and goes for regular checkups. After birth, the baby is given ART for a few weeks and is fed formula rather than breast milk. Once the infant is older, it is important that the mother not pre-chew the child’s food.)

The discovery of a functional cure for infants would affect a relatively small proportion of people living with HIV in Canada, but it could have a significant impact internationally, as more than 90 percent of HIV-positive children live in Africa and only a minority have access to ART.

Light at the end of the tunnel

It’s been more than 30 years since HIV was isolated by scientists, and at least 35 years since people around the world began dying of a mysterious wasting disease.

The past three decades have been punctuated with news of promising approaches to a cure—most of which have not borne fruit. But knowledge about the virus has been accumulating and scientists who have spent their lives studying HIV are excited about the present state of research.

Although it might not be right around the corner, a cure for HIV seems more and more possible. In fact, what will be needed is likely not a single cure but instead multiple cures. As Reinhard points out, an approach that might work for long-time survivors—people who have been living with HIV and taking treatment for many years—would likely differ significantly from a cure for newborns with HIV or a cure for recently infected adults.

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Peggy Frank

Do you think we’ll find a cure for HIV in your lifetime? 

It seems like we’re close. And I’m going to live another 40 years, so I do think we’ll find a cure in my lifetime.

The worst thing that could happen would be if we in North America become complacent because we can treat and control the virus so well that we forget how important a cure would be for people in those parts of the world where it is still hard to access treatment.

Once we have a cure, we will have millions of people to thank—those who did the research, those who tracked down the dollars, those who acted as guinea pigs...

If we do find a cure, how would it impact your life?

 If I was no longer HIV positive, I imagine that I would have more energy to tackle the global issues I’m passionate about. I would love to return to Africa, to work with people whose hope swells seeing others survive AIDS. I would love to set a few new life goals and get out there and break ground. I would take a moment each day to be grateful for what HIV has taught me.

[See Peggy Frank’s 7-foot martini glass.]

Robert Reinhard

Do you think we’ll find a cure for HIV in your lifetime?

Just as we couldn’t foresee that it would take so many years to find an effective vaccine, we can’t predict the success of cure research. But we now know a lot about the biological obstacles to eliminating HIV and have strong agendas to attack them. I’m more hopeful than ever before.

If we do find a cure, how would it impact your life?

 More than 35 million people worldwide have HIV. While each person would be able to enjoy their right to health and to a good life, the social impacts would be enormous and collective. To quote the poet John Donne: “Every man is a piece of the continent, a part of the main.”

Yvette Perreault

Do you think we’ll find a cure for HIV in your lifetime?

 From an existential perspective, I believe we will. I have to hope. Otherwise it’s too difficult for my activist heart to make sense of these past 30 years.

If we do find a cure, how would it impact your life?

Well, it won’t bring my dead friends back. And would a cure prevent my dear friends who are very sick right now from dying? It is a certainty that everyone will face death sooner or later (those of us who are HIV-negative too), but a cure would at least level the playing field somewhat.

Once a cure has been found, I imagine it will be like when a war ends: We will be able to count our dead, complete our mourning and wonder why some of us made the cut and others didn’t. I think I will finally exhale deeply and deal with whatever waves of deep sadness and rage surface. I will step back and pay careful attention to the memories of the past 30 years, which demand that I stop, reflect, make meaning and find ways to share stories with others who lived through this time. I’ll be looking for the legion hall-equivalent for weary AIDS activists!

[See Yvette Perreault’s Ask the Experts about grief.]

About the author: Ann Silversides is the author of AIDS Activist: Michael Lynch and the Politics of Community. She writes regularly about health policy issues and her article “First Do No Harm” in Maisonneuve magazine, about a Brockville, Ontario, coroner’s inquest into prescription painkiller related deaths, won the Canadian Medical Association award for excellence in in-depth feature reporting.

Illustration by Aaron McComony

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