A growing body of evidence indicates that inflammation and immune system activation associated with ongoing HIV replication has detrimental effects independent of CD4 cell count.

As recently reported, researchers analyzing the large SMART treatment interruption trial found that levels of certain biomarkers of inflammation and blood coagulation (clotting) -- including interleukin 6 (IL-6), D-dimer, and high sensitivity C-reactive protein (hsCRP) -- had an elevated risk of death. Furthermore, IL-6 and D-dimer levels rose during treatment interruption, while remaining stable in patients who stayed on continuous HAART.

In a study presented this week at the 9th International Congress on Drug Therapy in HIV Infection (HIV9) in Glasgow, Scotland, investigators sought to determine whether inflammatory and coagulation biomarkers are altered in HIV positive children and adolescents.

This cross-sectional analysis included a cohort of 88 pediatric HIV patients followed at Bambin Gesu Children's Hospital in Rome between December 2007 and June 2008. About 60% were female and the age range was 3 to 25 years; children with hepatitis B or C coinfection were excluded. Most (86%) were on combination antiretroviral therapy, and about 75% had HIV RNA < 1000 copies/mL and CD4 percentage > 25%; however, 70% had symptomatic (CDC class B or C) disease.

The researchers assessed levels of biomarkers including D-dimer, antithrombin, protein C anticoagulant, protein S anticoagulant, and C-reactive protein, and looked at their associations with HIV viral load, CD4 cell count, clinical disease stage, and current antiretroviral treatment.

Results

• D-dimer levels were significantly elevated in patients with HIV RNA > 1000 copies/mL.

• Reduced anticoagulant activity of C protein, S protein, and antithrombin also showed a strong correlation with higher viral load.

• 8% of patients had abnormally low protein C activity, while about 50% had low protein S activity.

• C-reactive protein levels did not differ significantly according to viral load, CD4 percentage, or disease stage.

• None of these biomarkers differed according to use of antiretroviral therapy.

Based on these findings, the investigators stated, "The higher anticoagulant activity present in symptomatic patients…could be explained by the treatment, and its related viral suppression."

However, they added, "no relation has been observed" regarding C-reactive protein levels.
"These preliminary data seem to confirm the same observation done in adult cohorts," they concluded, "but further studies are necessary to correlate such alterations with clinical events and to investigate the protective role of therapy in this particular population."

11/14/08

Reference
G Pontrelli, H Tchidjou, R Citton, and others. D-dimer and anti-coagulation activity markers in children and adolescents with HIV infection. 9th International Congress on Drug Therapy in HIV Infection. Glasgow, Scotland. November 9-13, 2008. Journal of the International AIDS Society 11(Suppl 1):P213. November 10, 2008.