Canada is falling behind when it comes to HIV research

Despite past success in keeping HIV (human immunodeficiency virus) in check, a recent rise in cases is creating new cause for concern. According to the Canadian Foundation for AIDS Research, Canada reported a 25 per cent increase in HIV diagnoses between 2021 and 2022 – the most significant rise in over a decade.

The European Union reported a similar trend, with a more than a 30 per cent increase over the same interval. That means thousands of people have been newly diagnosed with HIV – and these are just the cases caught by testing. Roughly one in 10 people who have HIV in Canada are unaware of their diagnosis.

A reduction in screening services may be one reason behind this decline. Other reasons HIV awareness may have been set back include the COVID-19 pandemic and a lapse in sex education among younger generations. New HIV cases are most commonly found in Canadians aged 30-39.

“The majority of the population thinks of HIV like it’s any other virus,” says Nicolas Chomont, HIV specialist and professor in the department of microbiology, infectology, and immunology at Université de Montréal. “This normalization contributes to a decline in prevention.”

These perceptions may result from a lack of public health campaigns about HIV. “No longer are people with HIV dying en masse,” says Sean Hosein, science and medicine editor for CATIE, an organization that houses HIV and hepatitis C information. “People can now live with the virus – and not transmit it.”

The development of the first anti-retroviral drugs in 1996 marked a turning point in HIV treatment. Highly active antiretroviral therapy (HAART), in which three or more anti-retroviral medications work together, controls the infection and helps people with HIV to live almost normal lives.

Today, HIV treatment is remarkably effective. People living with HIV can receive injections that are effective for up to two months. That’s all it takes – just the occasional jab.

“Treatment adherence is critical for people living with HIV,” says Mr. Hosein. “And many people have a hard time swallowing pills on a daily basis.” PrEP (pre-exposure prophylaxis) – that is, medication taken to prevent the HIV infection – has also undergone considerable advancement.

But anti-retroviral treatments must be taken for life. Just a few weeks off and the viral load proliferates in what’s called a viral rebound. What’s more, after several decades, this regimen has an inevitable effect on the body.

“Even if the viral load is controlled, people who have been receiving HIV treatment for some time are prone to comorbidities, such as heightened risk of cardiovascular disease,” says Éric Cohen, who held the Canada Research Chair in human retrovirology until 2015 as well as the director of the human retrovirology unit at the Institut de recherches cliniques de Montréal (IRCM). He has studied HIV for more than 30 years.

These health consequences pose a considerable burden to people with HIV. In 2011, the Canadian AIDS Society estimated the net value of economic loss at $1.3 million per person living with HIV. This assessment takes factors like loss of productivity and lower quality of life into account, among others. Adjusted for inflation, that estimate balloons to $1.7 million in today’s dollars.

An elusive foe

A complete cure is still the Holy Grail of HIV research. And that path is full of twists and turns. The virus is notoriously difficult to expel from the body, as it finds ample places to hide.

“HAART reduces the viral load by 99.99 per cent,” said Dr. Chomont. “The remaining 0.01 per cent of infected cells sink into the deep tissues of the spleen and lymph nodes – even the brain.” These reservoir cells keep the body in viral latency, even during treatment.

Dr. Chomont’s lab strives to identify where in the body the virus likes to hide. He and his team have discovered that infected cells can move to other organs, rendering extractive surgery moot. Analysing tissue samples donated by Canadians with HIV, they published their findings in the academic journal Cell Reports in 2023.

The goal of these studies is to eliminate viral reservoirs, but so far, results have been mixed. A new therapeutic approach in the last few years has investigated whether “waking up” viral reservoirs helps with attacking and removing them. Experts say this approach has had disappointing results.

“Attempts to eradicate HIV have resulted in, at best, a small reduction in reservoirs,” says Dr. Chomont. “From a clinical point of view, these results aren’t very productive. Whether someone has 100,000 reservoir cells or a million changes nothing about the fundamental problem.” Ideally, every reservoir would be eradicated.

Strategies for an HIV cure will likely have to rely on multiple approaches. For example, suppression of viral reservoirs could be coupled with immune modulator therapies. Because untreated HIV targets the immune system and weakens it over time, bolstering immune response may be key to successfully eradicating HIV.

Recent findings have drawn significantly on cancer research in surprising ways. Both diseases function similarly: groups of undesirable cells proliferate at advanced rates.

Certain cancer treatments, such as immunotherapy, have become the focus of many HIV research studies. Some biological therapies use monoclonal antibodies, which boost cancer patients’ immune systems so the body can rid itself of cancer. It follows that these synthetic cells could someday serve the same purpose in people living with HIV.

Another avenue being explored involves mRNA vaccines – the same ones developed during the COVID-19 pandemic. The U.S. biotechnology company Moderna launched a clinical trial in 2021 to put mRNA technology to the test against HIV. Phase 1 is still in progress.

“The COVID-19 health crisis has facilitated great strides in our understanding of vaccines,” says Dr. Cohen, “especially their structure and the complex role antibodies play. That said, COVID-19 is an acute infection that can be spontaneously cured – unlike HIV.”

There have been no reported cases of spontaneous recovery among people infected with HIV. However, three people in Berlin, London, and Düsseldorf were cured as a result of bone marrow transplants from a donor with a rare genetic mutation that bolstered HIV resistance.

Unfortunately, the mortality rate for this operation is between 20 and 30 per cent, making it a last resort option. The three patients also developed a treatment-resistant leukemia as a result of the transplant.

This is why HIV research moves at a snail’s pace: the risks of new treatments are huge compared with relatively well-tolerated anti-retroviral treatments. “We are, in respects, victims of our own success,” says Dr. Cohen. He nevertheless predicts major strides in the coming years.

“Emergent interventions will have gradual effects, working toward the eventual goal of putting the virus into remission,” he says. “Remission won’t be instantaneous, but may come after many years spent tracking viral loads in stabilized patients whose treatments have been conclusively terminated.”

Canada no longer in the lead

Significant investment in new scientific advancement is necessary if we want to build on this promising research. Canada, however, lags far behind other nations especially the U.S., which dedicates US$3 billion each year to HIV research.

Dr. Cohen is a front-row witness to this trend. He directs the Canadian HIV Cure Enterprise (CanCURE), a pan-Canadian research team that studies HIV persistence and the development of therapeutic strategies. He’s watched the Canadian Institutes of Health Research dissolve funding for HIV in recent years.

“At launch in 2014, CanCURE received up to $1.8 million in annual funding,” he says. “By 2019, that amount was reduced to $1.2 million. New granting parameters [for September 2024] say that we can only request an annual maximum of $750,000.” Meanwhile, he estimates that similarly sized U.S. teams are playing with “five times the funding” to address the same questions.

Funding wasn’t always so imbalanced. After HIV emerged in the 1980’s, it was Montreal-based researchers who developed one of the first effective treatments: 3TC. Also called lamivudine, this anti-retroviral drug – approved in the 1990’s – is one of the cornerstones of HAART today.

Initiatives such as the Réseau SIDA-Maladies infectieuses were also launched during this industrious era. For 25 years, this group of Quebec-based researchers developed a considerable bank of biological specimens, particularly those taken from people living with HIV. The bank enabled a number of research projects to be realized. The Réseau has since recently lost its funding from the Fonds de recherche du Québec.

However, Canadian researchers are still doing their part. “We’re focusing on areas less covered by research, on blind spots,” says Dr. Cohen. “Instead of chasing after low-hanging fruit, we’ve decided to be unique.” Others, including Dr. Chomont, rely on the National Institutes of Health in the U.S. to fund their HIV research.

The Government of Canada’s recent reinvestment in research and innovation has given researchers new hope. Even if no amount is specifically set aside for HIV research in the 2024 federal budget, improved funding at the master’s, PhD, and postdoctorate levels may facilitate student recruitment into HIV research labs.

Whether this is enough to enable new research, however, is not yet clear. “As you know,” says Dr. Cohen, “HIV has been relegated to second-rate status in favour of other fields of research, like artificial intelligence and neuroscience. This shift in focus makes it much more difficult to convince young researchers to work in HIV research than it was 30 years ago.” Past success is hard to replicate.

A few statistics:

 

1981: The year the first alarm was sounded on what would eventually be known as the biggest health crisis of all time, according to the World Health Organization (WHO).

39 million: the number of people worldwide living with HIV in 2022. (Source: UNAIDS)

62,790: the number of Canadians living with HIV at the end of 2020. (Source: Public Health Agency of Canada)

6,472: Number of Indigenous persons living with HIV in Canada in 2020. Though only five per cent of the Canadian population is Indigenous, Indigenous people make up 10.3 per cent of Canada’s HIV-positive population. (Sources: Public Health Agency of Canada; Statistics Canada)

19 in 100,000: Rate of HIV diagnosis in Saskatchewan in 2022. This rate is significantly higher than the national average of 4.7 in 100,000. (Source: CANFAR)