Symposium on HIV Infection, Inflammation, and Premature Aging

[Guest guest]

CFAR Symposium on HIV Infection,

Inflammation, and Premature Aging

I attended this symposium in San Francisco on

Tuesday, May 18. There was an impressive lineup of speakers. You can see the

program agenda at http://cfar.ucsf.edu/cfar?page=symposia-10-home. 

The speakers were top rate, and guest speakers (from outside UCSF) included

Victor Appay from Paris, Judith Campisi from the Buck Institute for Age

Research, and , University of Vermont.

The audience included many UCSF AIDS

researchers, which made for interesting questions to the speakers.

The entire symposium will be posted as a

webcast within the next few weeks.

Thanks to Goldman and Matt Sharp for

their review and comments on my notes.

There were many take-away points for me:

·

Senescence

is amazingly complicated at the cellular level and involves the accumulation of

cells that are in many ways non-functional. Senescence is thought to increase

our susceptibility to autoimmune disorders and cancers.

·

Inflammation

is a complex and poorly defined process.

·

Cancer

is a hyperproliferative process, in some ways the opposite of immune decline;

both occur in aging. Aging is distinct from disease. It makes people

susceptible to disease and degrades quality of life. Cancers appear to be a

separate process; some are related to habits or genetic factors; others are the

result of mutations accumulated through cellular division.

·

Environmental

factors can “shift the curve” of onset of age-related disease. The

use of antiretroviral therapies, particularly the nucleoside analogs, may be an

important “environmental” factor.

·

Carl

Grunfeld was, as usual, provocative. His main point was that HIV does not

“accelerate” aging. He argued that we need to identify the specific

disease processes. Maybe hepatitis co-infection accelerates aging when it

occurs together with HIV; maybe CMV infection does; maybe metabolic syndrome

does. To lump all of these together as “HIV-accelerated aging”

might cut off needed research into specific disease processes.

·

The

cancers with a viral cause (Kaposi’s Sarcoma and non-Hodgkins Lymphoma)

appear to occur earlier in people with HIV. But Hodgkin’s Lymphoma

appears later. How can we explain this?

·

Geriatric

medicine is not as far advanced as I had thought. Additional research on HIV

and associated illnesses could help advance our general knowledge of aging.

Atherosclerosis is considered a model for aging. A parallel process may occur

with all other organ systems.

·

We

need to develop measurements for the manifestations of aging. These include

comorbidities and functional problems, which constitute frailty. There is a

scale in common use but it does not include a component on clarity of thought

or memory.

·

We

need better markers of immune function. I strongly agree with this! The CD4

count is too blunt a tool, and at higher levels, more CD4s do not correlate

with improved immune responses.

·

With

highly refined viral load measurements, virus can be found in up to 80% of people

with HIV. We don’t know if this residual viremia is the result of new

production of virus or the release of virus from infected cells. This residual

viremia may be a cause of ongoing inflammation.

·

There

was also discussion of “leaky gut” and microbial translocation.

This topic is getting more and more attention and is clearly a source of

generalized immune and inflammatory responses throughout the body. My original

naïve understanding of this was an almost “physical” leakage from

the gut rather than bad bugs that should be killed by an effective immune

system in the gut (the Peyer’s patches, which are wiped out by HIV very

early in infection.)

·

Re

osteoporosis: vitamin D is currently seen as affecting a huge range of body

processes, and deficiency causes problems. Vitamin D deficiency is not an HIV

phenomenon, but is prevalent in the general population. Unfortunately, there is

no agreement on what levels of supplementation to use, and as yet, no evidence

that supplementation leads to any clinical improvements in any population.

·

Bone

remodeling is a very slow, continuous process; increases due to calcium

supplementation or other therapies take a long time to show up as increased

bone mineral density. However, studies of bisphosphonates such as fosamax have

shown very rapid decreases in fracture rates even in the absence of increases

in bone mineral density.

Thanks to the Gladstone Institute and CFAR

for offering this symposium with no registration fee, and thanks to Matt Sharp

for publicizing it.

[Guest guest]

" Carl Grunfeld was, as usual, provocative. His main point was thatHIV does not “accelerate” aging. He argued that we need to identify thespecific disease processes. Maybe hepatitis co-infection accelerates agingwhen it occurs together with HIV; maybe CMV infection does; maybe metabolicsyndrome does. To lump all of these together as “HIV-accelerated aging”might cut off needed research into specific disease processes."This is very important. The simple concept of "accelerated aging" is easy to market and sell, but it over-simplifies a very complex reality.JB