HIV-1 infection alters energy metabolism in the brain:contributions to HIV-associated neurocognitive disorders, 2019, Cotto et al

Paywall, https://www.sciencedirect.com/science/article/pii/S0301008218302168
Sci hub, https://sci-hub.se/10.1016/j.pneurobio.2019.101616

 

Well that was depressing reading for someone living with HIV.

Save this: "...implementation of a ketogenic diet [88, 212, 213], intranasal insulin treatment [214], or exercise [215] coupled with use of anti-inflammatory drugs may provide therapeutic benefits to PLWH."

 

The good news is that both factors contributing to HIV-associated Neurocognitive Disorder (HAND) can be mitigated by a careful choice of antiretroviral medication.

There are many of these such papers that make it sound like HAND is an inevitable consequence of HIV infection. It is not. I have read many of these papers, and they conflate quite different antiretroviral regimens and do not discriminate between PLWH who had HIV for many years before the advent of HAART and those who received HAART soon after seroconversion.

The two main factors that contribute to HAND are 1) the inability of an antiretroviral drug to penetrate the blood-brain barrier and 2) a negative impact of the antiretroviral drug on mitochondria. The ideal antiretroviral regimen will include at least 2 drugs that penetrate the blood brain barrier well, and no drugs with a significant negative impact on mitochondria.

Unfortunately, the widely disseminated treatment guidelines do not take these factors into account. Firstly, the treatment guidelines were based entirely on which antiretroviral drugs best reduce virus in the blood, with absolutely no consideration given to whether or not the drugs cross the blood-brain barrier. Secondly, the determination of which drugs negatively affect mitochondria were based on limited assays that only tested the drugs against the few mitochondrial proteins that were impacted by earlier generations of antiretroviral drugs. (AZT, ddI, d4t)

As a result of this short-sighted thinking, we still do not have sufficient research about which antiretroviral drugs cross the blood-brain barrier well, with conflicting results for even the most popular antiretrovirals. And we have misconceptions about the potential mitochondrial toxicity of some antiretrovirals. For example, Abacavir is widely held to be one of the safest antiretrovirals for mitochondria, since it showed virtually no inhibition of the mitochondrial proteins that were inhibited by earlier generations of antiretrovirals. Subsequent research that tested Abacavir against whole mitochondria, however, found significant toxicity.

 

Very interesting @Pyrrhus - I did not know there was such lack of clarity about ARVs and BBB and mitochondria, thanks for the info - makes me question my own regimen.

Segue slightly: I know lots of pwHIV yet do not know any with ME diagnosis (post-HIV). Are you aware of any, come across any research indicating such?

 

I don’t know of any pwHIV who developed ME post-HIV. I vaguely remember Dr. Chia mentioning that of the thousands of ME patients he had seen, about 4-5 of them had HIV.

But it’s important to remember that many of the ME diagnostic criteria consider HIV to be an exclusionary criterion. This means that doctors were prohibited from diagnosing ME by these diagnostic criteria if the patient tested positive for HIV.

 

I did not realize that. Presumably HIV is not the only exclusionary illness from getting a ME diagnosis.

I wonder how many people with an 'exclusionary' illness and ME symptoms, and do not get the ME diagnosis?

 

The point about exclusionary illnesses is that the illness would be expected to cover everything. It does not mean that if you have one you can't get the other. For instance if you have MS then feeling very fatigued is covered by the MS diagnosis you do not need to have CFS as well.

However if you develop PEM say then you may have ME as well as MS.

The problem is the diagnostic confusion that exists with ME and CFS and the lack of clear diagnostic tests. If you have had ME for 20 years then test positive for HIV you could have both but it would be harder to say you have acquired ME after having had HIV for 20 years.

Things are made worse by CFS being used to describe the symptom of fatigue nowadays.