A functional cure and the wider use of statins

Just as protease inhibitors were the groundbreaking science presented at AIDS1996, a ‘functional cure’ for HIV in the form of long-acting injectable antiretroviral therapy (ART) paired with broadly neutralizing antibodies (bnABs) may be long remembered as the big news from July’s IAS HIV Science Conference in Brisbane.

Statins as prevention for cardiovascular disease; and breastfeeding moving closer to U=U were other exciting announcements.

IAS2023 was attended by over 5000 delegates. The conference brought together the world’s leading scientists, researchers, clinicians, community advocates, government policy makers and pharmaceutical companies in the HIV response. 

Heather Ellis presented the welcome from community speech at the HIV Cure & Immunotherapy Forum, which was a pre-meeting at IAS2023

Heather Ellis presented the welcome from community speech at the HIV Cure & Immunotherapy Forum, which was a pre-meeting at IAS2023

A functional cure

Long-term injectable ART paired with bnABs was touted by some of the more optimistic HIV scientists at IAS2023 as a ‘functional cure’ for HIV.

Broadly neutralising antibodies bind to immune cells to neutralise the ability of HIV to embed itself and are made naturally in the bodies of some people after years of HIV infection. Over the last decade, scientists have figured out how to make these bnABs from proteins in the lab. They have made them even more potent, longer-lasting and effective on the many different strains of HIV in circulation. These lab-produced bnABs are non-toxic, have the potential to be produced in low-income countries, and may be self-administered. However, they are eventually washed out of the body and repeated infusions are needed.

Researchers see people with HIV receiving an infusion of bnABs paired with long-term injectable ART once or twice a year for a few years until the person’s own immune system learns how to stop HIV rebound as it emerges from the HIV reservoir, which would ultimately be cleared.

Research presented touted that this combo was highly possible as a functional cure, with the promise of finding a pathway to a cure and a vaccine in future years. But there was also hesitation. This is partly, because bnABs don’t work for everyone, especially those with well-established HIV reservoirs. More research is needed to have the therapy individualised. For those people diagnosed very close to HIV transmission, using bnAB infusions with long-term injectables, prior to the HIV reservoir being established was discussed as a promising strategy. 

This groundbreaking science is still very much experimental with major clinical trials continuing globally, including in Melbourne. If you are interested in being part of a trial visit the Victorian HIV Cure Database . For the latest on HIV cure science visit HIV Cure.

The future of HIV treatment

This combo of long-acting injectable ART paired with an infusion of bnABs had many scientists excited about it as the future of HIV treatment. Researchers presented findings from recent clinical trials that show HIV suppression can last 12 months on average, and up to 18 months in a few cases. And for the lucky few, viral rebound did not occur. However, these people referred to as post-treatment controllers (PTC), may have achieved their PTC status regardless. The reported rates of PTC ranged from 10 to 30 per cent from those who took part in clinical trials. The next step for researchers is to look deeper into the mechanisms behind PTCs and their innate ability to clear the HIV reservoir including how they produce their own highly effective bnABs.

This combo of bnABs and ART injectables, as the future of HIV treatment, will be life changing for people with HIV, especially for those who fear disclosure as they no longer need to hide pills. For others, who may struggle to remember to take daily pills, there would be  no more adherence worries. Adherence leading to drug resistance is a growing problem in many low-income countries – a fact that was often mentioned by researchers in their presentations on long-acting injectables. For those people with HIV who travel regularly or for months at a time, it will mean no more carrying bottles of pills and hiding medications from border authorities. However, while the long-term injectables paired with bNABs breakthrough is very promising, it is still only available in clinical trials which are continuing globally, including in Australia Talk to your HIV doctor if you are interested in being involved in a clinical trial of long-acting medication.

In Australia, people with HIV have access to injectable ART in the form of cabrotegravir paired with rilpivirine, which is a two monthly injection. It is only suitable for those people without drug resistant HIV—often those diagnosed in recent years. However, the long-acting injectable ART, lenacapavir, administered twice-yearly, suppresses HIV even for those with multi-drug resistant HIV, and is scheduled to be available in Australia in early 2024.

Insights into the HIV reservoir

There were many presentations on research that dived deep into the immune cells where latent HIV persists as the HIV reservoir. Findings presented showed just how smart HIV was at hiding inside the DNA of immune cells to avoid detection. While the outlook is decidedly pessimistic, scientists have gained a deeper understanding of the mechanisms used by HIV. Some researchers also presented findings on lessons learned from the science behind medicines and therapies used to treat other diseases and how this science can be applied to HIV. The blood cancer medication venetoclax and the use of liposomes as an immunotherapy to reduce inflammation in rheumatoid arthritis, which is still in experimental stages, were presented by researchers.

Statins to protect cardiovascular health

Another breakthrough at IAS2023 was the findings from the global seven-year REPRIEVE trial on the use of statins as prevention of cardiovascular disease for people with HIV at low to moderate risk. Not only do statins reduce cholesterol, but also low-level inflammation which occurs even when viral load is undetectable.

This research is a huge break-through for people with HIV, especially as we age as it is well known we have a higher risk of cardiovascular disease as a result of this inflammation. And this is especially true for women with HIV and the additional inflammation that comes with menopause. Women made up 35 per cent of the REPRIEVE trial, which enrolled 7769 people with HIV aged 40 years to 75 years. Findings presented showed the important benefit of statins for women and men with HIV. The trial, which closed early as there were no safety issues and the benefits outweighed any risk of prescribing statins, used pitavastatin, which is a moderate intensity statin and is suitable to use with ART. Some of the side effects of statin use is muscle-related aches and weakness, but in the study these side effects were mostly mild and only one per cent of participants withdrew due to these side effects. While pitavastatin is not yet available in Australia (release is due in early 2024), other statins that can be used with ART and give the same cardiovascular protection are available. Talk to your HIV doctor about whether or not statins should be part of your HIV treatment. Scientists at IAS2023 also presented emerging research that showed the potential of statins to help support ART in controlling HIV. But this science is still emerging.

Breastfeeding moves closer to U=U

Breastfeeding also moved a step closer to U=U (undetectable equals untransmissible) with the presentation of the updated WHO policy brief, which is key to supporting those countries where mothers with HIV are not supported to breastfeed and their only infant feeding option is formula. Formula is often expensive with supply issues in many low-income as well as high income countries. The term used in this presentation was ‘negligible’ risk of HIV transmission when the mother is on ART with a sustained undetectable viral load and is supported by healthcare providers.

However, in many low-income countries, viral load testing is not widely available as it is in countries like Australia so there are limitations in knowing if the mother has an undetectable viral load.  Researchers, clinicians and community all called for this lack of viral load testing to be urgently addressed not only for breastfeeding mothers and their babies but all people living with HIV to identify viral load rebound from drug resistance, which is often related to adherence issues. WHO researchers also presented findings that showed limited mixed feeding did not present any increased transmission risk. However, scientists called for more research into the impact of ART consumed by the baby via breastmilk over six months and 12 months of exposure.

Based on strong evidence from trials, researchers also announced that when a mother has an undetectable viral load and is on ART then PEP for newborns may not provide any additional benefit and is likely to be no longer necessary. They called for present guidelines globally to be changed. WHO are now updating their guidelines on breastfeeding for mothers with HIV, which are due to be released in early 2024. Talk to your HIV specialist who can advise you on these new findings with regards to PEP for newborns and the safety of breastfeeding.

HIV Community Collaborations:

A key theme in many of the sessions presented at IAS2023 was the importance of collaboration between community, scientists, clinicians, business and government in HIV science research design and implementation to end the HIV epidemic and eliminate AIDS by 2030.

A number of pre-conference sessions highlighted these community collaborations with several key events held:

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