poslink Issue 96, Spring 2021

Scaling up to a cure-for-all

by Jared Stern

Advancements in therapeutics have already cured three people living with HIV and given longer, healthier lives to millions more. But just how close is medical science to finding a cure for all? And what would this mean for ending the epidemic?

This year’s World AIDS Day is marked by the 40th anniversary since the first cases of AIDS-defining illnesses were clinically described in the United States of America. However, we know that many people were living with HIV prior to this. Retrospective analyses of samples from Robert Rayford, a 15-year old African American who died of pneumonia in 1969, indicate he had HIV and that his death was due to AIDS-related illnesses. Phylogenetic analyses of historical samples estimate that the pandemic strain of HIV crossed over from chimpanzees in Kinshasa as early as the 1920s.

It is crucial for us to remember these names and lives of people affected by HIV/AIDS long before we knew of its existence. People of colour have been centred in this epidemic since its origin and remain so today.

Modern antiretroviral therapies (ART) mean that people living with HIV have similar life expectancies to those not living with HIV, particularly if treatment is started early. We now know with certainty that people with undetectable viral loads will not pass on HIV to their sexual partners. These antiretroviral drugs have also been repurposed as PrEP to prevent HIV-negative people from acquiring HIV.

In an ideal world, if everyone living with HIV was taking ART and everyone at risk of acquiring HIV had access to prevention, we could completely eliminate all future transmissions – yet we know this is not the case. 37.7 million people will still be living with HIV and we cannot be forgotten. So, what to do? The clear answer, and a topic of much research including my own, is that of a cure for HIV and there are currently some incredibly innovative approaches in this area.

The aims of a cure generally fall into two camps: sterilising or functional. A sterilising cure completely removes all traces of HIV from the body, essentially meaning someone will be HIV-negative once again. A functional cure aims for ‘remission,’ preventing the virus from rebounding when someone stops taking medications.

Numerous people have had a sterilising cure already. Timothy Ray Brown (the “Berlin Patient”), Adam Castillejo (the “London Patient”), and the “Dusseldorf Patient” all received stem cell transplants from people with a delta32-CCR5 mutation – a natural mutation that renders people resistant to acquiring HIV. All three individuals stopped taking ART without viral rebound or any detectable HIV throughout the body.

Additionally, some people living with HIV can naturally control the virus without progression. Some can even maintain undetectable viral loads. These individuals are referred to as long-term non-progressors and elite controllers, respectively, and demonstrate what could be considered a functional cure. Taking these cases into account, the question shifts to whether a scalable cure for HIV is achievable.

One scalable cure approach takes precedence from the geographically-named cure cases by genetically editing a person’s own cells to be resistant. This is more scalable than transplantation which has a very high mortality rate, is very expensive, and requires people to take immunosuppressive drugs to prevent their bodies rejecting the transplant. We can also genetically edit the virus itself, mutating it so much that it is no longer infectious.

ART is lifelong because HIV can hide dormant in infected cells – a term we call latency. If our immune system can’t recognise these cells as being infected, it can’t eliminate them. The ‘shock and kill’ cure approach aims to reactivate hiding virus so that the immune system can recognise infected cells and kill them off. This would be done when someone is still on treatment so that awakened virus can’t go on to infect new cells. Other approaches aim to reinvigorate and retrain exhausted immune systems through medications, vaccination or genetic editing.

In contrast is the ‘lock and block’ approach. This strategy aims to make hiding virus even more deeply latent so that it never wakes up. Here, we may see a blurring between treatment and cure as longer lasting ART emerges. This is also an important area to research as current drugs do not actually prevent an infected cell from producing viruses but rather act to prevent new cells from being infected. Better HIV-suppressing drugs may help to lessen those comorbidities and increased ageing seen in people living with HIV.

Much research and refinement of these strategies is now underway to assess their viability. While the cases of sterilising cures show this is possible, ART-free remission which upholds the ethos of U=U is likely more achievable at scale, for now. Unfortunately, we cannot predict when a game-changing breakthrough will occur.

Other considerations remain, particularly around utility and palatability. For example, would we want a sterilising cure that didn’t render someone resistant to reacquiring HIV (like sofosbuvir for Hepatitis C)? This may mean maintaining adherence to ART (as PrEP) or other prevention technologies. We also do not know if a cure will prevent comorbidities and early ageing associated with low-level viraemia in people living with HIV.

Stigma and discrimination certainly factor into our motivation for a cure. Would we want a functional cure if people were still labelled as HIV-positive? Is such a cure desirable if discriminatory employment and immigration policies remain around the world? Alternatively, were someone to receive a sterilising cure and become ‘HIV negative,’ are we sure that this would end HIV stigma? And what effect would this have on our identity and connection to the HIV positive community?

In any case, factors impacting on quality of life for our communities such mental wellbeing, comorbidities and age-related conditions, financial insecurity, and social connection and relationships would still need to be addressed.

All in all, these considerations return us to the larger question of equity in the global HIV response brought to light by names such as Robert Rayford and the uneven burden of HIV-related morbidity and mortality across the world. The HIV cure space is an excitingly progressive field. It is important for people living with HIV, their clinicians, researchers and the broader community to have open and ongoing discourse to be best prepared for when a scalable cure is available.

The history of Futures: the changing story of HIV in Australia

by Jennifer Power, ARCSHS, La Trobe University and John Rule, NAPWHA

HIV Futures is the longest-running and largest survey of people living with HIV in the country. Through it, we can see how the story of living with HIV has evolved over the past twenty years. It is a unique and important, still unfolding, Australian story.

HIV Futures was established in 1997. This was a hugely significant time for people living with HIV. Highly Active Antiretroviral Therapy (HAART) had recently become available in Australia. People who had been acutely (often terminally) unwell were regaining health and many were looking to return to work and rebuild their lives. Although the way forward was not always clear, the HIV sector needed to shift focus toward supporting people to live well with HIV.

How has ‘health’ been understood?

In 1997, when the first HIV Futures survey was undertaken, the average age of HIV Futures participants was 39 years and the average length of time people had been living with HIV was 7.4 years. Just over 70% rated their general health as good or excellent.

However, health is a relative concept. In the same survey, 70% reported that their CD4 count was less than 500 copies/ml, meaning they had likely experienced some degree of immune system damage and resulting illness; and 19% percent had been diagnosed with an AIDS-defining illness.

This self-assessment of health is where we see the most dramatic change over 20 years. In 2019, the average age of participants was 50 and the average length of time people had been living with HIV was 15 years. Fewer than 3% had been diagnosed with advanced HIV disease (or an AIDS-defining) illness within the past 12-months. Despite this, around 70% rated their health as good or excellent – the same as in 1997.

Unlike the late ‘90s, where a subjective assessment of ‘good health’ was measured against the tragic health consequences of HIV in the pre-HAART era, in 2019 health was measured against concerns about mental wellbeing, stigma and the complexity of ageing-related conditions. This is good and bad news. Unquestionably, living into older age is a good thing, especially by the expectations people held for life and health in 1997. However, living long-term with HIV brings other stressors and challenges.

Work, income and poverty

Early in the epidemic, HIV had a devastating impact on many people’s capacity to work. This was evident in 1997, where more than half of HIV Futures participants were not in paid employment due to ill-health. The impact of this time was still evident 20 years later. In 2019, many people who had been living with HIV for up to three decades continued to experience financial hardship. High levels of poverty and housing insecurity have been a defining feature of all HIV Futures surveys. While this has begun to change, and in 2019 the majority of people aged under 50 were financially secure, poverty is still a major concern for many people living with HIV in Australia.

Relationships and stigma

In 1997, the word ‘stigma’ was not even used in the HIV Futures survey, although concerns about stigma were implicit in almost everything – from management and concealment of pill regimens to use of medical services. What really stands out in HIV Futures from 1997 through to 2019, is the impact that HIV-related stigma had on people’s relationships.

In 1997, just over half of HIV Futures participants indicated that they feared rejection by a potential partner or lover when disclosing their HIV status. Twenty years on, this percentage had not reduced. While such fears effect people in different ways at different points in their life, HIV Futures findings show that many people living with HIV have always held concerns about the possible ways that stigma can undermine their relationships with colleagues, family members, friends and lovers.

Now and the future – focussing on quality of life for all

Today there is a major focus in the HIV sector on supporting quality of life. What is evident in the findings from HIV Futures across the past 20 years is the reality that living with HIV intersects with core aspects of life: health, financial security, relationships and culture. Understanding quality of life is about understanding the complex ways that these intersections can change in responses to medical advances, investment in social support and care and challenging stigma.

In recent years, the importance of understanding the ways in which experiences of living of HIV intersect with cultural diversity and migration have become increasingly important. We know that the sector needs to expand its focus to ensure the HIV response meets the needs of people who are often excluded from, or invisible within, the HIV response – this includes migrants and refugees, people from culturally and linguistically diverse communities and Aboriginal and Torres Strait Islander people. To move in this direction, findings from the HIV Futures 10 survey will be augmented with a series of qualitative interviews with people living with HIV who have migrated to Australia. These peer-based interviews are being undertaken in partnership with NAPWHA and findings will be presented alongside HIV Futures 10 survey findings.

The aim of HIV Futures has always been to document and understand the contemporary experience of living with HIV. Now that ‘having life’ and living longer with HIV have been achieved, information from the next HIV Futures 10 will help us understand what it looks like to live with HIV today and into the future.