Certain biomarker for inflammation and coagulation in HIV positive patients have been associated with increased risk of death from non-AIDS diseases, such as cardiovascular disease, according to an article published in the open-access journal PLoS Medicine onOctober 20, 2008.

This study, called the Strategies for Management of Anti-Retroviral Therapy (SMART) trial, was performed under the auspices of the International Network for Strategic Initiatives in Global HIV Trials. The SMART examined approaches to treatment of HIV with Anti-Retroviral Treatment (ART): one with continuous treatment and one with intermediate treatment. In the intermediate treatment, ART was discontinued, except when CD4 immune cell count dropped to a certain range of concentration (between 250 and 350 cells per microliter).  The continuous treatment is the current standard, but if intermediate treatment is possible, it may help conserve drug cost.

However, though the study initially aimed to contrast these two treatment methods for AIDS, more subjects in the intermittent treatment group died from diseases not associated with AIDS, and the study was terminated ahead of schedule. To follow-up on this study, James Neaton of the University of Minnesota and colleagues reexamined the data to investigate the possibility that this death was due to an inflammatory response caused by the higher HIV levels during periods of ART interruption.

Blood samples were analyzed from people who had died in the study (85 subjects), and for each of these patients, blood samples from two matched controls who survived were analyzed and compared (170 subjects). Of the 85 deaths, 55 had been assigned intermediate ART and 30 had been assigned continuous ART. The samples were analyzed for biomarkers specific to inflammation or coagulation of blood.

Three of these biomarkers were associated with increased risk of death across both treatment groups: high-sensitivity C-reactive protein (hsCRP), interleukin 6 (IL-6), and D-dimer. Further, throughout the entire trial base, IL-6 and D-dimer levels were higher in the intermittently treated patients in the first month of the trial, while patients receiving continuous ART treatment had unchanged levels of these substances.

The researchers conclude that this association between inflammatory biomarkers and AIDS death risk from non-AIDS related diseases is important. “The magnitude of the association between these biomarkers and mortality is clinically relevant and reasons for it require further study,” they say. They note that, because the sub-study’s size was relatively small, it is important that further research be performed before clinical recommendations are made for patients on continuous ART treatments. However, they point out, this study brings forth the possibility for development of therapies capitalizing on inflammation and coagulation pathways.

Inflammatory and coagulation biomarkers and mortality in patients with HIV infection.

Kuller LH, Tracy R, Belloso W, De Wit S, Drummond F, et al.
PLoS Med 5(10): e203.
doi:10.1371/journal.pmed.0050203
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Written by Anna Sophia McKenney