HIV infection, inflammation and premature ageing

Webcasts from a symposium on this topic, held on 18 May 2010 by the Center for AIDS Research at the University of California at San Francisco, are available online.

Five talks addressing the intersection of HIV and aging have been posted, with more presentations from the afternoon session coming soon.

Meeting summary notes

Bob Munk, New Mexico AIDS Infonet

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 made a provocative main point 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 (Kaposis Sarcoma and non-Hodgkins Lymphoma) appear to occur earlier in people with HIV. But Hodgkins Lymphoma appears later. How can we explain this?

Geriatric medicine is not far advanced. 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 dont 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 naive 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 Peyers patches, which are wiped out by HIV very early in infection.)

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 alendronate (Fosamax) have shown very rapid decreases in fracture rates even in the absence of increases in bone mineral density.