Question

How does HIV and HIV meds affect the brain?

17 April 2012. Related: All topics, Living with HIV long-term, Opportunistic infections.

Answer

Answer: Simon Collins

The best way to answer this complicated question is to look at HIV and HIV drugs separately in terms of the brain.

HIV and the brain

HIV gets into the brain within the first few weeks of infection. However,  most people luckily do not seem to experience any direct symptoms from this. Most people are able to continue with day to day life so long as their CD4 count stays high.

If your CD4 count drops below 200, the risk increases for infections that can affect how you feel and think. If the CD4 count drops to below 100 and especially below 50, this includes HIV-related dementia.

If ARV treatment is when the CD4 count is above 350, these problems are very unlikely. Even if started late, HIV drugs can often reverse problems related to brain function.

So for people on effective and stable treatment, HIV does not seem to progress to damage the brain or cause symptoms. Most people continue to be able to lead a normal life.

Ongoing research is now looking at long term complications of HIV. Some researchers think that there may be small changes that we haven;t know about before. Just as getting older increases the risk of symptoms like memory loss, this risk may be higher if you are HIV positive, or it might occur at an earlier age.

The medical name for changes in brain function is neuro-cognitive impairment (NCI for short).

HIV meds and the brain

How HIV drugs affect the brain is difficult to study but it is the focus of a lot of research.

The brain is physically difficult to research because it is encased in the skull and surrounded by a fluid that is also difficult to test. This fluid is called cerebral spinal fluid – or CSF for short. There is a filter between the blood and the CSF called the blood-brain barrier (BBB).

In practice, the BBB only lets the smallest HIV drug molecules get in to the CSF and the larger compounds are blocked. One group of researchers has summarised which drugs are likely to cross the BBB using CSF penetrating effectiveness (CPE) score.

Table 1: Estimated CSF penetration of individual HIV meds (CPE score)

4=good CSF penetration; 1=little or no CSF penetration

This table is based on limited data though and sometimes the position of individual drugs changes as new research develops.

Some drugs can find another route into the brain and CSF that gets around the BBB, so this may not be the full story.

How important is it to use drugs that get into the CSF?

The answer to this question is not known. People using drugs that have low CSF penetration do not seem to be at higher risk of HIV brain-related illnesses compared to people using drigs that we think do get to the brain. However, in someone with NCI symptoms, guidelines recommended adding or switching to drugs that are more likely to get into the CSF.

Two other aspects of this research are important.

One is that drug levels in the CSF are only an indirect measure of whether drugs reach brain tissue. Measuring CSF is difficult enough. It involves a lumbar puncture (spinal tap) but is used because we cannot biopsy brain tissue directly. Really we need to know about whether drugs get into brain tissue (cells).

Another is that a few studies have suggested that drugs getting into the CSF also has the potential to cause side effects. There is even less data on whether this might be a long term concern. So far, again luckily, the balance of risk vs benefit seems to support getting in mat be better than not getting in, especially in someone with NCI symptoms.

Assessment and monitoring

Part of the difficulties about anything related to the brain is that changes in brian function can be difficult to measure and monitor. Extensive tests that take several hours or use difficult and expensive scanning techniques that are not practical for testing everyone in a clinic.

How you think and feel, including memory, can be affected by other things in your life. Brain function also changes over time in most people as we age.

The following three areas are used in the European EACS guidelines for assessing whether further testing might be needed.

Your doctor should also ask about these aspects of your health as part of routine monitoring, especially in older patients or in people with a low CD4 count.

Further reading

CHARTER study for details of 2010 CPE penetration score. 17th CROI, abstract 430.

http://www.retroconference.org/2010/Abstracts/39373.htm

PDF link

http://www.retroconference.org/2010/PDFs/430.pdf