Illustration by Dr Maya Dyveke Schou. Created with BioRender.com
A humorous interview to increase awareness about HIV.
Maya Dyveke Schou is a medical doctor at the Department of Clinical Medicine, Aarhus University and Department of Infectious Diseases, Aarhus University Hospital, Denmark. She is doing her PhD in HIV cure with a focus on immunotherapy as a strategy to control HIV.
Interviewer (INT): Welcome to you both. You are with us in the studio today as contestants in the world’s longest running hide and seek championship. Please introduce yourselves to our audience.
Immune cell (CELL): Sure, I’m just one humble immune cell, but I’m representing the whole immune system, today. I’m very happy to be here and get this discussion started!
HIV reservoir (HIV): Yes, it is about time that we get to voice our opinions. Today, I’m representing HIV within cells, also called the HIV reservoir. I’m calling in from a secure landline as I’m currently in hiding.
INT: HIV, you have been hiding for decades now. Where do you see yourself in five to 10 years?
HIV: Nice try. I am obviously not going to disclose my whereabouts. My plan is to just continue roaming in disguise.
INT: Immune cell, do you have any comments on that?
CELL: We are confident that we are going to find all the cells that contribute to the HIV reservoir, although it might take us some time. When we do find them, they will have it coming for them.
INT: What motivated you to enter the contest?
HIV: I saw it as an opportunity to travel! In the early days I could hide in plain sight because no one knew about me, but after they introduced antiretroviral therapy (ART), I had to go undercover. Nowadays, whenever I try to slip into a new hiding place, I am at risk of getting discovered.
CELL: HIV was disrupting the neighborhood and we had to enter the contest to get the situation under control. We are more confident with the situation now that ART is available because it prevents HIV from travelling around.
INT: Why continue seeking out HIV if it commonly stays in one place?
CELL: We realised that our favorite humans (e.g. hosts) must do a lot of work to maintain the situation. Humans must take ART every day to keep HIV under control and although this usually means they don’t spread it to others, people can still get a bit awkward around them. In addition, we sometimes see that long-term treatment can impact their bodily functions over time.
Also, this is a global contest, and some places don’t have reliable access to ART or are facing problems because HIV developed a way to outsmart the medication and became resistant. Finally, we are an ambitious group that is determined to win by either eradicating HIV completely or by locking it away for life so our humans don’t need to take daily medication anymore.
INT: Which hideouts are being investigated right now?
CELL: For years we have been thinking that HIV was mainly hiding inside specific immune cells called CD4+ T cells in either blood or lymph nodes, but we recently busted HIV hiding inside these other immune cells called macrophages and inside astrocytes, which are cells located in the nervous system. We are obviously excited about that discovery, but keeping our eyes peeled.
HIV: Yes, you are getting warmer.
INT: What would you say has been your biggest weakness throughout the contest?
HIV: Well, it is increasingly difficult to keep hiding, when so many people are trying to find you all the time. I never relax. I’m always on the run. Always looking for new ways to hide.
CELL: Honestly, our team members sometimes get exhausted and therefore become inefficient and lose their impact. The other day one of my mates got so tired and confused that he forgot what we were looking for. Can you believe that? After we have literally been searching for HIV’s hideouts for years.
INT: Do you have any bold additions to your hide and seek strategies?
HIV: This is going to be off script, but I have been working on a few strategies to avoid being discovered. I have fooled some of the immune cells to express proteins called immune checkpoints on their surface. These proteins make them exhausted and then it’s harder for them to find and fight me. Another strategy is securing my hideouts. The cell I’m currently hiding in is trying to get rid of me by self-destructing. I am stopping this by blocking the “self-destruct” signals, also called proapoptotic pathways. An easy escape.
CELL: Maybe not so easy. We have tried out so many cool strategies lately. We have been offered a bunch of tools that can roughly be divided into two main toolkits. One kit is filled with tools that make us better at finding HIV by boosting the fitness and orientation skills of individual members and increasing the number of members.
The other kit targets the HIV reservoir directly. This can force HIV out of hiding or make the HIV-occupied cells more prone to self-destruction. Although our tools are currently placed in one of the toolkits, some of them have actions that overlap both.
HIV: ……………..
INT: Thank you for sharing with us, this is all very exciting. In the meantime, it appears that we mysteriously lost the connection with HIV after you explained your search strategies. Do you have any last comments?
CELL: Ready or not, here I come!
Disclaimer: The humorous take on HIV in this article is purely meant for increasing awareness about HIV which remains a major global public health issue with ongoing transmission in all countries globally. According to the WHO, 39 million people were living with HIV at the end of 2022, with some countries reporting increasing trends in new infections when previously on the decline. There is still no cure for HIV. However, access to effective prevention, diagnosis and treatment enables people living with HIV to lead long and healthy lives. This article is an appetizer for the more thorough and undeniably drier article named HIV clinical trials aimed at HIV cure or remission: New pathways and lessons learned. We hope you enjoy reading it.
