Dr Jessica Robinson-Papp: Autonomic Neuropathy in People With HIV Needs More Attention

Autonomic neuropathy in people with HIV needs more study and attention, said Jessica Robinson-Papp, MD, MS, professor of neurology at Icahn School of Medicine at Mount Sinai.

The American Journal of Managed Care® interviewed her while at the American Academy of Neurology 2023 conference about a study she co-authored about this condition as a predictor for morbidity and mortality.

This transcript has been lightly edited for clarity.

Transcript

You were recently part of a study that linked HIV-associated autonomic neuropathy to hypertension, higher viral load, and more abnormal liver function. Can you talk about this study and the implications of these findings a bit more?

About 10 years ago, we conducted a study. I've always been interested in peripheral neuropathies because I'm a neurologist, and my fellowship training is in peripheral neuropathy. One form of peripheral neuropathy, the one that people are most aware of, is referred to as distal sensory polyneuropathy (DSP), which is characterized by numbness, pain, tingling in the feet. But there are also nerves that innervate all of our internal organs, and those are called autonomic nerves. When people have autonomic neuropathy, which they often do when they have this DSP in the feet, they can have a whole bunch of a variety of odd symptoms that are hard to pin down to any one organ system, and that's because all those nerves go to lots of different organ systems.

They may have dizziness when they stand up, their blood pressure may be volatile, they could have gastrointestinal symptoms, heat intolerance; lots of different things that you wouldn't necessarily think was neurologic. So, we became interested back then in simply documenting the presence of autonomic neuropathy: how many patients with HIV have it? Is it common, or not? That's where we started. That study did show indeed that it was quite common and was associated with the DSP in the feet. So, if you had the DSP in the feet, then you are more likely to have the autonomic neuropathy as well.

Time went by, and we were very curious to see after 10 years had gone by, what happened to our patients who were diagnosed with autonomic neuropathy. The reason we were curious about this was because in other conditions that have a lot of autonomic neuropathy, particularly diabetes, that autonomic neuropathy is associated with poor outcomes over time. The main reason for that is cardiovascular outcomes. The heart has a lot of autonomic innervation and if that's not working properly, you can get arrhythmias. But also, there's a very interesting area that we're particularly focused on, which is innervation of the immune system. So, there's another idea that, if the autonomic nerves are not working properly, then your immune function may also not work properly, which is particularly relevant to people living with HIV.

This was a chart-based study. Most of our patients stay in care in our system over long periods of time. We have a very large health care system. So, we were able to manually follow these patients from the time of their first study visit, forward in time until the present date. We stopped right before [the] COVID-19 [pandemic] because we figured at that point, probably outcomes would be very muddy, with the COVID pandemic, so we did it to the very beginning of 2020.

We just simply saw and looked for, first of all, did anybody die? Were there cardiovascular morbid events? And then other major organ systems like liver and kidney. What we found was that the patients who had autonomic neuropathy at baseline had an increased hazards ratio of having one of these bad outcomes and that ratio was was 3.8. So, [it] pretty significantly increased. Even when we controlled for their baseline medical status, for example, if you were sicker at baseline, you'd have a greater likelihood of having a bad outcome, even when controlling for those things, and the patients with autonomic neuropathy still had more of those outcomes.

So, what we can do about that is not clear yet, because there's no particular treatment for the autonomic neuropathy that we could make it go away in the beginning and avoid those outcomes. The way I took it is that it is supportive of the idea that this is an important thing to study and to learn more about.

How can cardiac, renal, and hepatic surveillance be improved for patients with HIV-associated autonomic neuropathy, in a way that works for the patient and will help them adhere to this surveillance?

I do not know, that's very tough. Before you even before you even get to surveillance, there's a lack of mechanistic understanding of how the autonomic neuropathy might even lead to those other organ complications. In the heart, that's a little better understood, at least in the context of diabetes. But for the kidneys, and especially the liver, we don't really know what that mechanism is. So to understand how you would develop a surveillance program, I think you'd have to know what you would be looking for first. I think the short answer there, is that more work is needed to understand mechanism before taking that into the clinic.

Reference

Kwon PM, Lawrence S, Figueroa A, Robinson-Papp J. Autonomic neuropathy as a predictor of morbidity and mortality in people living with HIV: a retrospective, longitudinal cohort study. Neurol Clin Pract. Published onlibe March 27, 2023. doi:10.1212/CPJ.0000000000200141