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November 7, 2011

Low Levels of HIV in the Blood Aren’t Connected to Inflammation or Death

Low-level viremia—HIV in the bloodstream in amounts below the level measured by standard tests—is not associated with inflammation or death, according to a November 2 study on PLoS One. The researchers, based at the San Francisco VA Medical Center and the University of California at San Francisco, found that the increased immune activation and coagulation (blood thickening) experienced by people living with HIV and taking antiretroviral medications (ARVs) are not caused by such viremia. This finding, senior investigator Phyllis Tien, MD, said in an accompanying announcement, “means that we need to focus on other possible mechanisms by which HIV increases inflammation and coagulation.”

Previous research has shown that HIV-positive people whose virus is suppressed by ARVs still experience increased immune activation and inflammation, which can elevate the risk of cardiovascular disease (CVD), clotting and stroke. The cause has remained unclear, leading some to assume that it results from the low-level viremia documented in people whose HIV registers undetectable (50 to 75 viral copies per milliliter of blood, depending on which test is used).

In the current study, the researchers write, they expected to find an association between low-level viremia and certain biomarkers known to indicate increased risk of CVD and mortality. Instead, they found no correlation between such low-level viremia and the three biomarkers—elevated interleukin (IL-6, a protein related to inflammation), fibrinogen (a protein involved in clotting) and C-reactive protein (CRP also related to inflammation). They did, however, find that higher levels of HIV in the blood (above 10,000 copies per milliliter, substantially above the level of undetectable) were associated with increases in two biomarkers: IL-6 and fibrinogen.

The research was conducted on blood samples from 1,116 HIV-positive people in the Study of Fat Redistribution and Metabolic Changes in HIV Infection (FRAM), a long-term study of people living with HIV in the United States. The samples were scrutinized using a newly approved test from Roche Molecular Diagnostics, capable of detecting HIV levels below 20 copies per milliliter. In addition to the findings regarding IL-6, CRP and fibrinogen, the tests found no association between low-level viremia and increased risk of death.

The researchers caution that their study has limitations, including that it was observational, that the blood plasma samples available for testing were small (possibly calling into question the readings of less than 20 copies per milliliter), that biomarkers were measured at only two points in time, and that information on cause of death was lacking.

Their findings, they write, suggest the need for further research to determine the specific ways that HIV promotes inflammation and increased risk of mortality. The research also suggests the need to reinvestigate some assumptions. For one thing, they write, the fact that they found no association between CRP and HIV levels could call into question the significance of C-reactive protein as a reliable marker of HIV inflammation.

Search: San Francisco VA Medical Center, University of California at San Francisco, viremia, coagulation, blood thickening, cardiovascular disease, clotting, stroke, blood

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