By Dr Rachel Pascoe and Dr Maya Schou
Overall summary
People living with HIV (PLWH) need to take medication (also known as antiretroviral therapy (ART) every day to stop HIV from replicating and causing disease progression. However, some rare people can keep the virus suppressed without medication and they are known as HIV controllers. For many controllers, their protection seems to come from their very effective immune responses against HIV. Therefore, one of the strategies proposed for curing HIV is to boost the immune cells of PLWH so they can control HIV in the absence of ART, just like the controllers.
In a recent study, researchers at the University of Melbourne used the immune-enhancing drug, pomalidomide, to boost immunity against HIV. The researchers used cells donated by people with HIV and showed that pomalidomide strengthened key immune cells and improved the killing of HIV-infected cells in the lab. Based on these promising results a clinical trial, named PEACH, is now underway to test whether pomalidomide can help people living with HIV maintain control of the virus without needing daily ART treatment.
What is pomalidomide?
Pomalidomide is a drug that improves immune responses and is approved for the treatment of bone marrow cancer and a rare type of cancer called Kaposi sarcoma. Pomalidomide increases the production of interleukin-2 (IL-2), a molecule that supports the stimulation, expansion, and longevity of immune cells. The drug is a capsule that is taken through the mouth once a day and is generally well tolerated, with minimal side effects.
What did the researchers find in the lab?
The researchers found that pomalidomide strengthened both key branches of the immune system:
- Innate immunity, by improving the function and killing capacity of Natural Killer (NK) cells—the body’s first line of defence.
- Adaptive immunity, by stimulating the expansion of HIV-specific Killer T-cells, which directly target and destroy HIV-infected cells.
In short, pomalidomide increased the number of immune “soldiers” and made them better fighters against HIV.
What does this mean for an HIV cure?
Many people living with HIV experience immune dysfunction (a state where immune cells are overstimulated and exhausted), even with suppressed viral levels in blood. Dysfunctional immune systems increase the risk of other illnesses, including infections and certain cancers. Pomalidomide both reduced immune dysfunction and boosted immune responses towards HIV. Pomalidomide therefore can support better control of HIV as well as help restore overall immune health. Pomalidomide is just one agent being explored as an immune-enhancing agent as part of efforts to find a safe, scalable, and accessible cure for HIV.
Testing pomalidomide in people – the PEACH Study
PEACH (Pomalidomide as an immune-Enhancing Agent for the Control of HIV) is a clinical trial that investigates the use of pomalidomide in healthy people living with HIV. Specifically, this study will explore if pomalidomide can strengthen the body’s own immune system to fight HIV.
The study consists of two phases. Participants will be randomly allocated to receive pomalidomide or a placebo (a capsule with no active drug in it).
Phase 1 – Participants will receive a capsule of pomalidomide or a placebo once daily for one treatment course of 21 days. All participants remain on their usual ART regimen. Blood samples will be collected to see how the immune cells react to pomalidomide while HIV is controlled under ART.
Phase 2 – Participants will be asked to pause their ART, and receive pomalidomide or placebo for two treatment rounds, each consisting of 21 days. This is to understand what happens to the immune responses and control of the virus when pomalidomide is given in the absence of antiretroviral medication. Blood samples will be collected to closely monitor virus levels, and participants will be called in for weekly or fortnightly safety visits with a doctor.
This study will inform us about the use of pomalidomide in people living with HIV and whether the treatment can strengthen the immune system’s response to HIV and help keep the virus under control for longer when HIV medication is paused.
The clinical trial started enrolling participants this year in Aarhus, Denmark and will be running at Royal Melbourne Hospital and Monash Medical Centre in Melbourne, Australia.
Read the recently published study.
Read more about the PEACH study.
If you would like to take part in PEACH, or find out more about it, please email HIV-trials@unimelb.edu.au.
