The Quest for the HIV Cure

Is there hope for a cure? Read about the Canadian HIV Cure Enterprise and the global effort to conquer HIV

July 17, 2015

A lot has happened since HIV, the virus that causes AIDS, was discovered in 1984. By that time, thousands of people had already died from AIDS-related illnesses and new cases were being reported all over the world. Discovery of the virus – by researchers in the United States and in France, working separately – was a cause for celebration. If the virus could be pinpointed, surely it could be stopped.

Unfortunately, stopping the virus has proven to be difficult.

HIV attacks the immune system and ultimately leaves the body vulnerable to infections and diseases that it would normally be able to fight off. The virus is a troublesome target because it basically turns an infected cell into its own factory, tricking it into making more and more copies of the virus until the cell dies. Those copies of the virus can then infect other healthy cells, so the cycle continues. Stopping that cycle is critical, and this understanding led to the development of antiretroviral therapy (ART). The first ART drug was approved for use in 1987, but the real breakthrough happened in 1996 when combination ART – or highly active antiretroviral therapy (HAART) – was introduced. These new, powerful drugs dramatically increased the lifespan of people living with HIV and can control the virus quite well by attacking infected cells that are busy making virus copies, but ART isn’t a cure. The virus hides out in what scientists call “reservoirs”, where cells are infected but are not actively producing HIV. These “latent” cells are not targeted by ART drugs – even the improved ones that we have today – so they can become HIV factories again if an individual stops treatment.

Photo: Dr. Éric A. Cohen

“ART is a lifelong therapy, which creates a lot of challenges,” explains Dr. Éric A. Cohen, who leads the Canadian HIV Cure Enterprise (CanCURE) and is a CIHR-funded researcher at the Institut de recherches cliniques de Montréal. These challenges include the side effects of long-term treatment, such as accelerated aging and cardiovascular, bone and kidney disease. “There are also economic and logistical considerations,” he continues, “as 35 million people are living with HIV and only half have access to treatment.”

In the quest for a cure, however, ART still plays an important role. Starting ART early can reduce the size and complexity of those virus reservoirs, and the hope is that smaller reservoirs will be easier to tackle with a so-called “kick and kill” approach that involves activating the hiding virus and boosting the immune system to recognize and destroy infected cells. If this approach is successful, it would lead to what is called a “functional cure” – or a state of sustained HIV remission – in which ART could be discontinued without any risk of having the virus rebound. In other words, even without eradicating the virus completely, a functional cure would offer lifelong control of HIV without lifelong drug therapy.

The challenge lies in finding all of those reservoirs in order to target the latent virus. Unlike cancer cells, which behave differently from healthy cells, the reservoir cells don’t stand out. Although researchers have identified many of the anatomical reservoirs (including the brain, the gut, and the genital tract), they are still working to identify all of the tissues and cell types involved.

With funding from the Canadian Initiative for HIV Cure Research – a partnership between the Canadian Institutes of Health Research (CIHR), the Canadian Foundation for AIDS Research and the International AIDS Society – CanCURE is contributing to the global understanding of these reservoirs and how the virus remains latent within them. The team brings together biomedical researchers and clinicians from 10 universities across Canada, as well as a community liaison to contribute the perspective of people living with HIV.

“This is not the type of project that one person can do in a lab and come up with a cure,” Dr. Cohen explains, noting that CanCURE also works with international scientists, community organizations, biotech companies, and other Canadian research teams working on different aspects of the virus. “Only with a very concerted effort and a multidisciplinary, systematic approach can we conquer HIV in the not-so-distant future.”

Since 2012, thanks in large part to the work of the International AIDS Society, there has been a global push to coordinate efforts to find a cure for HIV. Research teams around the world are working on specific lines of inquiry, and CanCURE is no exception. The Canadian team is studying macrophages, which are cells in the immune system known for gobbling up pathogens, because HIV targets those cells and may be able to stay latent in them.

“Our focus is complementary to others, but it doesn’t overlap,” Dr. Cohen notes. “So, this is a unique and important contribution from Canada.”

Although he cautions against raising expectations, Dr. Cohen remains optimistic. “We have proofs of principle that a cure is possible,” he says, “and growing availability of new and emerging technologies. All of this makes me believe that now is the time to mount an all-out effort to find a cure and finally bring the global AIDS epidemic to an end.”

For more information about CanCURE, visit their website.

For more information about HIV in Canada, visit the Healthy Canadians website. A timeline highlighting the history of HIV in Canada is also available from the Canadian AIDS Treatment Information Exchange (CATIE).

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