Mihiri Weerasuria
Is a cure for HIV on the horizon?
A breakdown of the Research priorities for an HIV cure: International AIDS Society Global Scientific Strategy 2021
The landscape of HIV care has dramatically shifted over the past few decades. What was once a terminal disease has been transformed by the immense efforts of people with HIV (PWHIV), community groups, researchers, and clinicians into a chronic illness not unlike diabetes or asthma. With proper monitoring and medication HIV is controllable and even untransmittable. But curable? Not yet.
Finding a HIV cure remains a high priority for PWHIV and care providers. Even though HIV is now manageable with medication, treatment must be taken for life. Around the world, many people have difficulty accessing HIV medication or still face intolerable side effects. The International AIDS Society (IAS) published their second consensus on the priorities in HIV cure research in late 2021. The priorities underscore some of the remaining challenges researchers face in the search for a cure. The document reflects on over 170 scientific studies and provides a roadmap to an HIV cure. It details where we’ve travelled so far, but also the obstacles ahead. By understanding what we’re up against, PWHIV, providers, and researchers from around the world can work together to progress towards an HIV cure.
Why is finding an HIV cure so hard?
A major challenge in curing HIV outlined in the IAS report is what is known as the ‘HIV reservoir’. After infection, HIV circulates in the bloodstream. A certain amount, however, hides away, hibernating in other cells and organs in the body. This is the HIV reservoir.
At the moment, HIV treatments can suppress HIV in the blood. Treatments can suppress blood virus to the point where it is undetectable and a person cannot transmit further. Unfortunately though, they cannot target the virus hibernating in the reservoir. This hibernating HIV can wake up at any time and replicate, leading to rebound infection if HIV medication is stopped. Therefore, a big piece of the puzzle in finding a HIV cure is understanding the HIV reservoir. We now know that the HIV reservoir begins to form within weeks of infection and that it constantly changes over time. Many factors impact on the HIV reservoir, including when a person started HIV treatment and their biological sex.
Four strategies to clear the HIV reservoir
If we can find a way to clear out, neutralise or change the reservoir, we might be able to cure HIV infection. So that’s exactly what researchers around the world are trying to do. The IAS report outlines four main strategies to achieve this.
The first strategy is colloquially known as ‘shock and kill’. ‘Shock and kill’ aims to clear out the HIV reservoir by waking up dormant virus (the ‘shock’). This allows HIV medications to find and eradicate it (the ‘kill’). The second strategy is ‘block and lock’. This strategy aims to stop the dormant cells in the HIV reservoir from ever waking up. A third strategy is ‘reduce and control’. This aims to make the HIV reservoir smaller and train the immune system with vaccines or antibodies to control HIV without life-long medication. The fourth strategy is to use gene therapy to remove HIV from infected cells in the reservoir. To complicate matters, scientists must ensure that any treatments target only the HIV reservoir, leaving healthy immune cells alone.
The case for hope and the road ahead
While this all may sound like science fiction, there are some recent major advances in HIV cure research. To date, four people have achieved sustained HIV cures using stem cell transplants. This is a very difficult and risky procedure, which unfortunately is not something that would be feasible for all PWHIV. There are also more and more examples of ‘elite’ and ‘exceptional’ controllers. These are people who, for some reason, keep HIV suppressed without medication. While these cases are uncommon, they are hugely intriguing! Scientists are closely examining what makes these people distinct in the hope of making a breakthrough in cure research.
The IAS recognise that finding a cure requires close collaboration with PWHIV and HIV-led community groups. To put it simply, cure research depends on the generous and selfless contributions of PWHIV who participate in scientific studies. The IAS report highlights how PWHIV must be empowered to guide how cure research is conducted at every step. Any research must be ethical, safe, and broadly represent all PWHIV. By doing this, we ensure that all PWHIV can benefit from cure research.
Over the next decade, researchers hope to learn more about the HIV reservoir. This will help to devise new ways to target and remove it to cure HIV. There is sure to be further research into emerging cure strategies such as immunotherapy and gene therapy. These strategies, which have absolutely revolutionised cancer therapy, have potential to do the same for HIV medicine.
Overall, we need more robust, large scale HIV cure-focussed clinical trials designed and conducted in partnership with PWHIV. We also need more funding and infrastructure for HIV cure research in the countries where the bulk of HIV infections occur. In future, we hope to see more cases of people who have achieved a sustained cure whilst off HIV medication. However, the ultimate goal is a HIV cure that is widely accessible, acceptable, and affordable for all. For now, the search for a HIV cure continues. While many challenges remain, together, we are on our way.
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