Want to receive publications straight to your inbox?

CATIE
  • Reports have suggested that HIV may be progressing more rapidly in Saskatchewan.
  • Researchers analyzed the genetic sequences of HIV among people in the province.
  • They discovered strains of HIV that have adapted to some people’s immune defences.

The immune system consists of a network of cells, tissues and organs, all organized to help defend the body from harmful germs and tumours. However, for the vast majority of people who become infected with HIV, this virus is quickly able to subvert the immune system’s defenses. Furthermore, HIV changes, or mutates, relatively quickly. This high rate of change makes it more difficult for the immune system to mount a successful response against HIV. As a result, if HIV infection is left undiagnosed and untreated, the immune system becomes relentlessly weakened and about 10 to 12 years after initial infection life-threatening infections and cancers occur—the hallmark of AIDS—in adults. The period between initial infection and the development of AIDS in untreated HIV infection can vary somewhat depending on a person’s genes, the strength (or virulence) of HIV and the presence of co-infections such as hepatitis C virus, among other factors.

HIV in Saskatchewan

In the province of Saskatchewan, a concentrated HIV epidemic has emerged. The average rate of new infections in Saskatchewan is about twice as high as in the rest of Canada and among the highest in North America. According to researchers, about 60% of new HIV infections in Saskatchewan are spread by sharing equipment for injecting street drugs. About 80% of people living with HIV in this province self-identify as Indigenous.

Reports from Saskatchewan suggest that HIV-related injury to the immune system is accelerated among some people in that province. Also, a report from the Saskatchewan Ministry of Health estimated that about 50% of people who were newly diagnosed with AIDS between 2007 and 2016 had died.

Taken together, this suggests the possibility that strains of HIV circulating in Saskatchewan may be more virulent in some people. To investigate this possibility, researchers in Saskatchewan and British Columbia collaborated on a study to better understand HIV and its impact in Saskatchewan. Researchers analysed changes in a gene of HIV collected between 2000 and 2016 in Saskatchewan, B.C. and other parts of Canada and in the United States. The data analysed could not be linked to individuals and consisted only of the HIV genetic sequence and the date that the HIV sequence was collected.

Their research suggested that strains of HIV in Saskatchewan have adapted to variants of the genes that help control the immune system’s response to this virus.  Moreover, it appeared that HIV strains in Saskatchewan had specifically adapted to immune system responses that are most common among people who have HIV and many who subsequently became HIV positive. The relationship between a person’s genes and the immune response to HIV is explained later in this bulletin.

Key findings

Strains of HIV in Saskatchewan have been adapting to the population in that province. Over time, HIV appears to have increasingly developed the ability to evade the immune defences in many people in this province. This ability of HIV to evade the immune response has likely led to a faster rate of immunological injury. This means that people who become HIV positive in Saskatchewan are more likely to become ill faster than people with HIV in other parts of Canada or the U.S, if they don't take and stay on HIV treatment (ART).

The adaptation by HIV to a person’s immune response depends on the presence of certain genes in that person. In the present study, HIV appears to have adapted to certain genes most commonly, but not exclusively, found among Indigenous people in Saskatchewan.

Implications

The study’s lead researchers, Jeffrey Joy, PhD, at the BC Centre for Excellence in HIV/AIDS and the University of British Columbia, and Zabrina Brumme, PhD, at Simon Fraser University, said that the findings suggest at least the following:

  • People who engage in condomless sex and/or inject street drugs should undergo regular HIV testing.
  • People who test positive for HIV should be swiftly linked to care where they can receive an offer of treatment. 
  • People who test negative for HIV should receive culturally competent counselling about ways to reduce their risk for infection with HIV, including harm reduction services, opioid substitution and access to PrEP (HIV pre-exposure prophylaxis).

According to Drs. Joy and Brumme, the good news is that HIV-positive people in Saskatchewan who are infected with these strains of HIV will respond well to HIV treatment and can experience long, healthy lives similar to that seen in many other HIV-positive people on ART and in care in Canada.

Dr. Joy noted that while the immune response and genes that HIV has adapted to are most commonly found in Indigenous people, they are also found in non-Indigenous people.

The findings from the present study will hopefully energize efforts to help more people in Saskatchewan stay healthy and reduce the spread of HIV.

Why did HIV adapt in Saskatchewan?

A group of immune system cells called T-cells help fight HIV in the body. Furthermore, the ability of HIV to evade the effects of T-cells is highly linked to certain genes associated with the immune system. In individuals not taking ART, HIV mutates relatively rapidly and the chance of it developing a way to evade the immune response is almost inevitable. That is why for the vast majority of people with HIV, ART is essential to keeping them alive and in good health; their immune system cannot be solely relied upon to contain HIV.

To get an idea of which immune gene variants are expressed in Saskatchewan First Nations residents, Drs. Brumme and Joy drew upon previously published studies. Upon comparing how common these gene variants are in Saskatchewan to those defined in other populations elsewhere in North America and globally, it was apparent that the diversity of genes that affect the immune response among Saskatchewan residents at greatest risk of HIV is relatively restricted. This lack of genetic diversity is likely a result of the effects of colonialism on Indigenous people that began around 500 years ago.

According to other scientists who study genes, history and societies in North America, “both archaeological and historical records indicate that European contact and colonialism initiated a significant reduction in the Indigenous population size through warfare, enslavement, societal disruption, and especially widespread epidemic disease.” This caused a dramatic reduction of Indigenous people, particularly women. Such a massive reduction in the population would have resulted in diminished genetic diversity.

As a result of the relatively reduced genetic diversity concerning genes associated with the immune response, it has been easier for HIV to adapt and overcome immune responses in people in Saskatchewan. Furthermore, according to researchers in B.C. and Saskatchewan, it appears that strains of HIV that are highly adapted to genes associated with the immune response “are being more widely and frequently transmitted than those [strains of HIV] with lower levels of adaptation [in Saskatchewan].”

Acknowledgment

We thank Drs. Jeffrey Joy and Zabrina Brumme for helpful discussion, research assistance and expert review.

Resources

Original research article

HIV Prevention and Control Report for 2016 – Saskatchewan Ministry of Health Population Health Branch

Canadian Aboriginal AIDS Network (CAAN)

Reports from the National Centre for Truth and Reconciliation

The epidemiology of HIV in Canada – CATIE fact sheet

Canada makes some progress on HIV but much work lies aheadCATIE News

Canadian study finds increased risk of death among HIV-positive Indigenous peopleCATIE News

Exploring viral suppression rates among some Indigenous people who started ARTCATIE News

—Sean R. Hosein

REFERENCES:

  1. Kinloch NN, Sanche S, Wong A, et al. High levels of adaptation to host cellular immunity in a concentrated North American HIV epidemic. In: Program and abstracts of the 22nd International Conference on AIDS, 23-27 July 2018, Amsterdam, Netherlands. Abstract THAA0102.
  2. Brumme ZL, Kinloch NN, Sanche S, et al. Extensive host immune adaptation in a concentrated North American HIV epidemic. AIDS. 2018 Sep 10;32(14):1927-38. Available from: https://journals.lww.com/aidsonline/Fulltext/2018/09100/Extensive_host_immune_adaptation_in_a_concentrated.3.aspx
  3. Mónaco DC, Dilernia DA, Fiore-Gartland A, et al. Balance between transmitted HLA preadapted and nonassociated polymorphisms is a major determinant of HIV-1 disease progression. Journal of Experimental Medicine. 2016 Sep 19;213(10):2049-63.
  4. Carlson JM, Du VY, Pfeifer N, et al. Impact of pre-adapted HIV transmission. Nature Medicine. 2016 Jun;22(6):606-13.
  5. Carlson JM, Le AQ, Shahid A, et al. HIV-1 adaptation to HLA: a window into virus-host immune interactions. Trends in Microbiology. 2015 Apr;23(4):212-24.
  6. Kløverpris HN, Leslie A, Goulder P. Role of HLA adaptation in HIV evolution. Frontiers in Immunology. 2016 Jan 18;6:665.
  7. Katoh J, Kawana-Tachikawa A, Shimizu A, et al. Rapid HIV-1 disease progression in individuals infected with a virus adapted to its host population. PLoS One. 2016 Mar 8;11(3):e0150397.
  8. Bryce PH. The story of a national crime: An appeal to justice for the Indians of Canada. Report. 1922. Available at: https://nctr.ca/reports.php
  9. O’Fallon BD, Fehren-Schmitz L. Native Americans experienced a strong population bottleneck coincident with European contact. Proceedings of the National Academy of Sciences USA. 2011 Dec 20;108(51):20444-8.
  10. Pepperell CS, Granka JM, Alexander DC, et al. Dispersal of Mycobacterium tuberculosis via the Canadian fur trade. Proceedings of the National Academy of Sciences USA. 2011 Apr 19;108(16):6526-31.
  11. Rutherford GW, Lifson AR, Hessol NA, et al. Course of HIV-I infection in a cohort of homosexual and bisexual men: an 11-year follow-up study. BMJ. 1990 Nov 24;301(6762):1183-8.
  12. Feinberg MB. Changing the natural history of HIV disease. Lancet. 1996 Jul 27;348(9022):239-46.