Immunology and Inflammation: An Update From the 1st International Workshop on HIV & Aging

This is part of a series of articles summarizing presentations from the 1st International Workshop on HIV & Aging, which took place in Baltimore, Md., from Oct. 4 to Oct. 5, 2010. Jump to the table of contents to see the other articles in this series.

Alan Landay, Ph.D., from Rush University Medical Center in Chicago, Ill., reviewed data on what happens to the immune system as people age. Memory CD28 negative immune cells decrease, which hurts the immune system's ability to fight pathogens based on prior, archived experience that it had built up through our lives. However, Landay explained that the number of memory CD4 cells in the average 50-year-old person with HIV is similar to the number of such cells in 70-year-old HIV-negative people.

Landay also brought up an interesting term: "inflammaging." Immune activation occurs with aging and seems to be higher in people with HIV, even if their HIV viral load is suppressed. This activation creates inflammatory responses and decreases the ability for the immune system to fight pathogens, causing "aging" of the immune system, which is also called immune system "senescence." This immune activation also decreases the elasticity of arterial walls, which may increase a person's risk for cardiovascular disease.

De-accelerating this early aging process in HIV-infected individuals could reduce the risk of age-associated problems that result from inflammation and immune activation. Successful HIV treatment is presently is the most effective immune deactivator, since it helps restore a person's natural (or "naive") T-cell population. However, naive T-cell recovery during antiretroviral therapy is suboptimal, and long-term treatment often fails to return levels of immune activation and inflammation to normal. Therefore, antiretroviral therapy may not be the best candidate to reverse senescence.

Another approach being investigated is to decrease inflammatory cytokines by using TNF inhibitors like pentoxifylline. Another mechanism could be controlling the way toxic LPS proteins get into the bloodstream from the intestines, which as I mentioned earlier is a process that may be involved in immune insult and activation.

Yet another strategy may involve using antibiotics to balance the intestinal flora. A U.S. AIDS Clinical Trials Group study is evaluating rifaximin, an antibiotic (approved for the treatment of travelers' diarrhea) that does not absorb easily into the bloodstream. Other options might be products that modify the intestinal flora, such as prebiotics or probiotics.

Russell P. Tracy, Ph.D., reviewed how the presence of HIV infection increases inflammation. However, he noted that increased HIV viral load has not been correlated with increased inflammation. In the SMART study, inflammatory markers such as D-dimer increased in the absence of HIV medications. (Cardiovascular events were 49 times more likely to occur in people with higher-than-normal D-dimer. Other cytokines, such as IL- 6 and C-reactive protein, also increased cardiovascular risk, but to a lesser degree.)