HIV-positive people who have elevated levels of two blood inflammatory proteins, fibrinogen and high sensitivity C-reactive protein (hsCRP), have a higher risk for premature death than people with lower levels of the two proteins, according to a study published in the November 1 issue of the Journal of Acquired Immune Deficiency Syndromes. These data add further weight to the theory that chronic inflammation is a significant factor in illness and death in people with HIV.

Inflammation is a normal process that occurs in the body in response to infection and to damaged or defective cells. In fact, the symptoms of the flu or common cold—fever, achiness, swollen glands—are all related to inflammation. When inflammation becomes chronic, however, vital organ systems, such as the blood vessels, heart, kidneys and liver, can become damaged, which ultimately increases the risk of serious health problems and death.

Researchers are finding growing evidence that chronic inflammation is common in people with HIV, and that HIV itself may be driving chronic inflammation. To shed further light on this topic, Phyllis Tien, MD, from the University of California at San Francisco, and her colleagues examined stored blood samples from the Fat Redistribution and Metabolic Change in HIV Infection (FRAM) study. The FRAM study ran from 2000 to 2002 and was designed to study lipodystrophy in 1,183 HIV-positive people.

In the current study, Tien’s team tested the blood samples for levels of fibrinogen and hsCRP and studied whether increased levels of these inflammatory markers predicted early mortality. To accomplish this, the team segmented the study participants based on both their fibrinogen levels and their hsCRP levels: in each case, those with the highest levels were grouped together, as were those with the lowest levels and those with moderate levels.

Tien and her colleagues found that both inflammatory proteins were highly significant as independent predictors of premature death—over and above other cardiovascular and HIV disease risk factors. People with the highest fibrinogen levels were more than three times as likely to die prematurely as those with the lowest levels. People with the highest hsCRP levels were nearly four times as likely to die early. Researchers also noted a trend suggesting that people with high levels of both proteins had poorer survival than people with high levels of only one protein, but the difference was small enough that it could have occurred by chance.

Tien and her team also segmented the results based on CD4 count. They did find that people with lower CD4s were more likely to have high fibrinogen levels and to die than people with high CD4s. The authors also found, however, that high fibrinogen levels were tied to an increased premature death risk even in people with CD4 counts over 500.

The authors caution that it is too early to suggest using either of these inflammatory markers as a means to predict which HIV-positive people might be most at risk for illness and death. They state, however, that these results do support the notion that inflammation is a driving force in illness and death in people with HIV.

Ongoing studies are testing whether common medications, such as aspirin and cholesterol-lowering statins, can lower inflammation in people with HIV. To that end, the authors conclude: “Investigation is needed to determine whether interventions to reduce fibrinogen and CRP levels might decrease mortality risk in HIV-infected individuals.”