Illustration by Kiho Tanaka
By Laura Rikard-Bell
When we talk about HIV, we often focus on the cells it most easily infects— those in the blood. But the virus is incredibly versatile—it can also infect and live in cells that are in other parts of the body including in tissues and hide there. One of these hiding places is in a type of immune cell called macrophages.
What are macrophages?
Macrophages—whose name comes from Greek for “big eaters”—act like the body’s patrol dogs, constantly scanning their surroundings for anything unusual. Much like a curious, hungry dog that sniffs and chews on whatever it finds, they ingest and break down bacteria, debris, and dying cells, helping to fight infections and repair tissues.
They are long-lived and highly resilient, making them essential for our health. But these same qualities can also make them an ideal hiding place for HIV.
HIV hides and survives in macrophages
Like other immune cells, macrophages can carry virus that remains hidden from both the immune system and treatment— a state known as latency.
This matters because if antiretroviral therapy (ART) is stopped, the virus wakes up and can go on to infect other cells. Some studies even suggest that macrophages alone are the source of ongoing infection under certain conditions. This tells us that macrophages are not just passive bystanders—they may play an active role in keeping HIV in the body.
Macrophages are built to last
Macrophages are incredibly diverse. Depending on where they are in the body, they can behave very differently. This means strategies designed for one type of macrophage may not work as effectively in other macrophages. In other words, there is no “one‑size‑fits‑all” solution when it comes to eliminating HIV.
They are also built to survive. Because their job is to eat potentially harmful material, they can tolerate stresses that would kill other cells (they have strong stomachs!). Once infected with HIV, they can avoid detection by the immune system and resist being cleared, allowing them to persist for long periods.
On top of this, many types of macrophages live in hard‑to‑reach areas like the brain or lungs, where some drugs cannot get to. This means that cure strategies may need specialised delivery approaches to reach these hidden cells.
Hope for clearing hidden HIV in macrophages
Excitingly, new approaches to study macrophages are emerging. One uses lab-grown 3D models called organoids to better model macrophages in tissues without needing to take samples from people. These systems can help researchers identify subtle differences between infected and healthy cells, helping to design strategies that target only the macrophages carrying HIV.
Another major advance is in drug delivery. Technologies such as lipid nanoparticles (tiny fat-like particles that can carry drugs around the body), are being designed to deliver treatments directly to hard-to-reach tissues where macrophages live.
Importantly, most researchers now agree that achieving an HIV cure will likely require combination approaches that target multiple cell types and viral hiding places at once.
Together, these advances are helping to build a more complete picture of how HIV persists in the body. Macrophages are an important part of this picture. By understanding how the virus hides in these cells, we can design more targeted and effective strategies to better control, or hopefully eliminate, HIV.
Laura Rikard-Bell is a PhD student at the Burnet Institute in the Infection, Inflammation and Innate Immunity group, led by Dr Anna Hearps.
