The Slow Decline: An Update on Neurological Complications Among People With HIV

I interviewed Bruce Brew, M.D., who spoke on neuropathogenesis at the Workshop for New Investigators and Trainees as the 18th Conference on Retroviruses and Opportunistic Infections opened in Boston, Mass., on Feb. 27. The video of the interview, which was produced by the International Foundation for Alternative Research in AIDS, is below (video by Jim Thompson):

In the interview, Brew recapped three key points that he made in his presentation:

• The need for biomarkers that can identify people who are stable on successful antiretroviral therapy, but who perhaps have slight, yet stable, neurocognitive impairment.
• The need to understand why some patients with controlled virus have cognitive deficits that may be evolving.
• The need to understand the overlap among various HIV-related complications that may have an effect on the brain, such as drug toxicities and cardiovascular disease, so that physicians might intervene earlier and make use of therapies from other disease entities.

We spoke about some of the key issues in neuropathogenesis. Brew discussed the utility of CD4+ cell counts, concluding that although they have some limited utility, they are very imprecise as indicators of neurocognitive impairment. In general, higher is better, but there appear to be some virologically controlled patients with central nervous system (CNS) symptoms -- symptoms that can sometimes worsen.

Nadir CD4+ cell count might be important for people off, or prior to, treatment, Brew said. However, he acknowledged that the target level keeps shifting. Is it 200 cells/mm³? 350? 500? We don't know.

We discussed the issue of CNS penetration of antiretrovirals and its importance, which is still under debate. Some of the best-penetrating medications are also the most toxic to the brain, for example zidovudine (AZT, Retrovir). Evidence is slim, but accumulating, that better CNS penetration may lead to better clinical outcomes.

Brew mentioned the need to be aware of therapies in related fields, such as multiple sclerosis, and to be ready to apply any learnings where possible.

Finally, he said that after a period in which there was almost no interest in research into CNS issues -- it was assumed that potent antiretrovirals would eliminate the CNS problems -- there is now growing interest in this area of scientific exploration.

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