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and Hepatitis.com Coverage of the
17th Conference on Retroviruses and
Opportunistic Infections (CROI 2010)
February 16 - 19, San Franciso, California
Inflammation and Immune Activation Linked to Increased Mortality Risk in People with HIV
Phyllis Tien and fellow investigators with the Fat Redistribution and Metabolic Change in HIV Infection (FRAM) Study looked at the relationship between mortality and blood levels of the inflammation biomarker C-reactive protein (CRP) and the coagulation biomarker fibrinogen among 922 American FRAM participants over 5 years.
Both CRP and fibrinogen are released as part of the inflammatory and clotting cascades that occur with development of atherosclerosis, a build-up of cholesterol, immune cells, scar tissue, and other material in the arteries. When blood flow through the narrowed arteries becomes too restricted, this can cause a heart attack or stroke.
A majority of participants (about 70%) were men, the median age was about 42 years, and 40% were current smokers. About 90% had used ART, about 80% had undetectable viral load, and the average CD4 count was around 350 cells/mm3.
Based on these findings, the researchers concluded, "Elevated levels of fibrinogen and CRP were strong and independent predictors of 5-year mortality risk. Fibrinogen and CRP remained independently associated with higher odds of death regardless of the degree of immunosuppression."
These findings suggest "an important role for inflammation in mortality beyond demographic, cardiovascular, and HIV-related factors," they continued, and "inflammation remains an important factor even in those with relatively preserved CD4 cells."
Turning to a resource-limited setting, Peter Hunt from the University of California at San Francisco and colleagues assessed the effect of immune activation among 500 people starting ART in the Uganda AIDS Rural Treatment Outcomes (UARTO) study.
In contrast with FRAM participants, this group had an average age of 34 years, about 70% were women, and the median CD4 count was much lower at 133 cells/mm3. Results were compared with those from an ongoing San Francisco cohort, but the 2 groups were not well matched with regard to either demographics or HIV disease status.
positive Ugandans have higher CD8 activation levels that HIV positive
San Franciscans both before and during suppressive ART," the researchers
stated, adding that it was unclear whether the difference could be explained
by genetic factors, viral factors, or concurrent infections.
In 2 other studies presented at the conference, researchers also reported links between inflammation or immune activation and mortality. Investigators with the INSIGHT collaboration found that participants in the FIRST study who had elevated baseline levels of CRP and the fibrosis biomarker hyaluronic acid were more likely to progress to AIDS, develop immune reconstitution inflammatory syndrome, or die within the first month after starting ART.
treatment interruption trial, elevated levels of the pro-inflammatory
cytokine interleukin 6 (IL-6) and the coagulation biomarker D-dimer
higher risk of non-AIDS death among HIV/HCV coinfected patients
with impaired liver function, as indicated by elevated hyaluronic acid.
Uganda Study: Univ of California, San Francisco, CA; Joint Clinical Research Center, Kampala, Uganda; Massachusetts General Hosp, Harvard University, Boston, MA; Mbarara Univ of Sci and Tech, Uganda; California Dept of Public Health, Richmond, CA.
A Choi, A Zolopa, and others. Inflammation and Mortality in HIV-infected
Adults: Analysis of the FRAM Study Cohort. 17th Conference on Retroviruses
and Opportunistic Infections (CROI 2010). San Francisco. February 16-19,
2010. Abstract 725.
P Hunt, J Martin, I Ssewanyana, and others. Impact of CD8+ T Cell Activation on CD4+ T Cell Recovery and Mortality in HIV-infected Ugandans Initiating ART. 17th Conference on Retroviruses and Opportunistic Infections (CROI 2010). San Francisco. February 16-19, 2010. (Abstract 306).