Expert explainer: Why is a cure for HIV so elusive?
Schulich researchers share progress and challenges in ending the HIV epidemic
By Cynthia Fazio, November 29, 2024
Globally, an estimated 39 million people live with the virus, UNAIDS set a goal of ending HIV transmissions by 2030. (Anna Shvets/Pexels)
Schulich School of Medicine & Dentistry researchers are on the cutting-edge of the study of HIV, working toward treatments and a better understanding of how the virus works.
Finding a cure is no easy feat. But there is progress.
The theme for this year’s World AIDS Day on Dec. 1 is “Take the rights path: My health, my right!” In 2021, the Joint United Nations Programme on HIV/AIDS adopted a goal of ending human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) as public health concerns by 2030. To help achieve this goal, UNAIDS created the 95-95-95 targets, aiming for 95 per cent of people living with the virus to know their HIV status, 95 per cent of people who know their status to be receiving HIV treatment and 95 per cent of people on treatment to be virally suppressed.
Schulich Medicine & Dentistry professor Jessica Prodger studies ways to prevent HIV transmission to address the epidemic in sub-Saharan Africa and why certain individuals are more susceptible to the virus. Schulich Medicine & Dentistry professor Jimmy Dikeakos and postdoctoral researcher Mitchell Mumby study various parts of the HIV virus and how viral proteins control the immune response within infected individuals. They spoke with Western News about the progress towards meeting the UNAIDS goals and why a cure for HIV remains so elusive.
Western News: What is HIV?
Jimmy Dikeakos (JD): HIV is a fairly small and simple structural virus but it’s also a very complicated virus. When expressed within infected cells, it can trick the immune system into not knowing it’s there. HIV is within the retroviruses family and hides in latent reservoirs, which makes it difficult to treat. If left untreated, it can lead to AIDS.
Jessica Prodger (JP): This virus infects the cells that provide us with immunologic memory – these are some of the same cells that contribute to lifelong protection elicited by childhood vaccination.
What makes HIV so difficult to cure?
JP: HIV is difficult to cure because one part of the virus’ life cycle is to integrate its own DNA into the human DNA of the cell it is infecting. These cells are very long-lived and can lie dormant for long periods of time. As a result, the HIV DNA inside them also lies dormant. If these cells become active again, the HIV DNA inside them can make a new virus that is released from the cell and can infect new cells or be transmitted to another person. However, while the cell is dormant, our immune system cannot detect the HIV DNA hidden inside the latent reservoir.
Currently, the medications we have available to treat HIV only stop new infections from occurring, but they do nothing against the HIV DNA hidden inside the human DNA. Additionally, our bodies have many safeguards against damage or mutations to our DNA, and we have no natural system to hunt out and excise non-human DNA.
Removing or permanently silencing this HIV DNA, or the cells that harbour it, is the challenge of HIV cure research.
What are the current treatments to help people living with HIV?
JD: A group of drugs called antiretroviral therapies (ARTs) inhibit the steps of the virus’ life cycle. They block the ability of an enzyme called reverse transcriptase or integrase to function. This treatment can halt replication of most of the virus and helps individuals lead a much healthier life.
Mitchell Mumby (MM): In recent years, ARTs have shown remarkable promise as a preventative measure through pre-exposure prophylaxis (PrEP). Those at risk of acquiring HIV can take PrEP, and when adherence is maintained, HIV transmission becomes exceedingly rare. However, traditional PrEP formulations require a daily pill, which presents challenges for long-term adherence and increases the chances of HIV transmission.
A recent study trialed a twice-yearly injection of a new treatment called Lenacapavir among young women in South African and Uganda, resulted in zero cases of HIV transmission. This innovation could greatly increase adherence to PrEP and reduce transmission rates.
The pressing challenges lie in ensuring access to this revolutionary PrEP regimen in regions of the world and communities where HIV transmission remains prevalent.
How much progress has been made towards ending HIV and AIDS as a public health concern?
JD: Globally, we have made huge strides in the last decades. There are now more than 25 ARTs that people living with HIV can have access to. There have been major education initiatives to encourage individuals to get tested. Unfortunately, in certain parts of the world and even in Canada, there is still a lot of stigma associated with HIV, which means not everyone will want to get tested to have access to these treatment strategies. There is still a long way to go in terms of education for everyone to understand people living with HIV who are receiving treatment can live an improved life.
What needs to be done to achieve the 95-95-95 targets by 2030?
MM: Achieving these targets is less a virologic challenge and more so a socio-cultural and economic one. To achieve the 95-95-95 targets by 2030, significant and sustained investments in testing and access to ARTs are essential, both for treating HIV-positive individuals and as a preventative measure through PrEP.
HIV disproportionally affects key populations around the world, including men who have sex with men, intravenous drug users, sex workers, adolescent girls and young women. At-risk groups sometimes avoid seeking care due to fear of discrimination or even imprisonment in places with strict laws against homosexuality, sex work or drug use. Because ART is required for life, the cumulative lifetime cost is significant for both individuals and at the population level, making programs that ensure ART access essential, especially in low- and middle-income countries.
Achieving the 95-95-95 targets will require widespread educational and testing programs and integrating HIV care into existing health infrastructure.
JD: Some of the biggest hurdles will be to enhance and develop the curative strategies, but also to really make sure everyone who’s infected knows they’re infected. We need to remain hopeful and optimistic. It’s important to strive towards these targets and the goal of ending the epidemic.
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Source: Western News
https://news.westernu.ca/2024/11/expert-explainer-why-is-a-cure-for-hiv-so-elusive/
"Reproduced with permission - Western University "
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