Rupert Kaul is a clinician scientist whose research focuses on mucosal immunity and HIV transmission and a world leader in HIV research and medicine

December 3, 2024

By Sunitha Chari

December 1, 2024, marked World AIDS Day, and forty years since the discovery of the human immunodeficiency virus (HIV) and its causal link to acquired immunodeficiency syndrome (AIDS). With current treatment, AIDS is no longer the public health emergency that it once was and tremendous strides in HIV research over the last forty years have given us antiretroviral (ARV) therapies that enable people with HIV to have a normal life span and live normal lives.

In addition, ARV medications can be used effectively to prevent HIV transmission.

At the recent AIDS 2024 Conference and HIV Research for Prevention Conference, results from phase 3 clinical trials demonstrated that a long-acting injection of an HIV-targeting drug called lenacapavir given every six months to people at risk of HIV infection was nearly 100% effective in preventing infections. However, lenacapavir is not the first drug to be used for preventing HIV infections.

To help us learn about new ARV drugs, their potential and the challenges that remain, we spoke to Rupert Kaul, a member of the Emerging and Pandemic Infections Consortium and an expert in infectious diseases and HIV medicine. Kaul is a clinician scientist at the Toronto General Hospital Research Institute, the former head of the division of infectious disease at UHN,  and a professor in the departments of medicine and immunology at the University of Toronto’s Temerty Faculty of Medicine. His research group focuses on understanding the interactions between genital and rectal microbiomes, immune responses and HIV transmission.

EPIC: What are the current treatments available for someone living with HIV?

RK: ARV therapies for someone living with HIV generally combine two to three drugs that target different aspects of the virus life cycle. The standard treatments available in Canada combine these two to three medications into a single tablet that can be taken once a day. We also have an injectable regimen, which is a combination of two injections (cabotegravir and rilpivirine) given every two months.

EPIC: From treatment to prevention, how is the standard of care changing?

RK:  We have known for many years that ARV drugs can be used not only for the treatment of HIV infections but also as pre-exposure prophylaxis (PrEP) to prevent infections in people at risk for acquiring HIV. Truvada is a tablet that contains two ARV medications (tenofovir and FTC) and is widely used around the world as PrEP. When taken properly Truvada reduces risk by 90 to 95%, and there is no doubt that many infections have been prevented with proper usage.

Recently the medication cabotegravir, administered as a single injection every two months, was shown to be more effective than Truvada in preventing HIV infections. While there are many reasons for this, an important one is that it can be hard to remember to take the Truvada tablets, and this is much less of an issue with an injection every two months. However, while cabotegravir injections are approved in Canada for PrEP, insurance does not cover it which means that this very effective medicine is underused here.

EPIC: What about the newest studies with long-acting injection, lenacapavir?

RK: Lenacapavir is a new type of ARV medication known as a capsid inhibitor that is given as an injection once every six months. It is the only long-acting injectable so far shown to prevent HIV infections. It works by interfering with HIV’s protein shell at multiple points throughout the viral life cycle. In very recently completed phase 3 clinical trials, lenacapavir was shown to be more potent than Truvada, preventing nearly 100% of HIV infections in heterosexual women, cisgender gay and bisexual men, and transgender men and women.

EPIC: What are some of the challenges in making these long-acting injections widely available for HIV prevention?

RK: The task of scaling up access to this new drug is a formidable one and includes regulatory approval and permits for generic manufacture in under-resourced global regions where HIV is endemic. Expansion of manufacturing capacity is needed, as is the public health infrastructure to identify people who will benefit from receiving the injection and to get it to them. The skill sets needed to design the drug, test it and scale up access are very different, so teamwork across multiple disciplines and geographical boundaries is absolutely crucial.

EPIC: What about the public reaction to PrEP?

RK: Acceptability and uptake of Truvada PrEP are quite high in Canada, particularly among men who have sex with other men. However, sustained uptake among other at-risk populations has been low for a number of reasons, both here in Canada and globally. One important barrier is the pervasive stigma against HIV that prevents people from seeing themselves as being at risk, or from accessing these medications even if they do realize they are at risk.

EPIC: What are some strategies to reduce stigma and encourage people to use PrEP?

RK: After 40 years of medical and scientific advances, HIV stigma continues to be a tremendous barrier that prevents people from seeking the treatment and care they need. However, when people learn that with current treatments a person living with HIV will have a healthy life and lifespan, cannot transmit the virus to their partners, and can have a family and a career just the same as anybody else, this knowledge definitely reduces stigma. Therefore, while we develop these fantastic new treatments and prevention technologies, we need to make sure that everybody knows about them – not only people living with and at risk for HIV, but also society at large.