icon-folder.gif   Conference Reports for NATAP  
 
  5th IAS Conference on HIV Pathogenesis, Treatment and Prevention
July 19th-22nd 2009
Capetown, South Africa
Back grey_arrow_rt.gif
 
 
 
Association between activation of inflammatory and coagulation pathways and mortality during long-term follow up in SMART
 
 
  IAS Capetown July 2009
Reported by Jules Levin
 
from Jules: Investigators followed patients beyond the 2 years of the study and found elevated inflammation markers are associated with death in this longer term followup just as it was in the <2 year shorter term followup. So what causes inflammation. Outside HIV chronic viral diseases are associated with increases in inflammation markers. In HIV despite undetectable HIV viral load inflammation could persist but I think controlling HIV replication with undetectable viral load improves chance to limit inflammation. But still we know replication and activation persists even when HIV viral load is undetectable & I think that is an important contributor to inflammation. As well, I think senesence plays a role in causing inflammation. Several studies show shortly after HIV-infection senesent phenotype emerges in patients and although little research has been done it appears that full suppression by HAART improves but does not reverse senesence, still we need better research to understand and explore this because perhaps earlt HAART or for some reason in some patients successful HAART may reverse senesence, we don't know. These factors are in my mind crucial contributors to early non-AIDS events and deaths due to these non-AIDS events, and are key to accelerated aging in HIV. With the aging patient population in HIV I expect we will see increasing non-AIDS comorbidities: cancers, bone disease, kidney disease, CVD, and brain disease/cognitive impairment including an increased risk for alzheimers & other serious CNS diseases, and increased premature mortality. Its estimated that by 2015 50% of HIV+ individuas in the USA will be >50 yrs old, now its about 20%.
 
N. Paton, The INSIGHT SMART Study Group
 
MRC Clinical Trials Unit, London, United Kingdom
 
Background: Activation of inflammatory and coagulation pathways (as shown by elevated interleukin-6 [IL-6] and D-dimer respectively) was associated with early mortality in SMART. We aimed to determine whether this association persists with longer follow up.
 
Methods: A nested case control study was conducted using the full follow-up data set of 5472 SMART patients (CD4+ count >350 cells/mm3 at study entry). Patients who died from any cause were included as cases, and were further classified as early deaths (≤2 years after randomization, n = 95) or late deaths (>2 years, n = 71). Two controls were selected for each case, matched for country, age, gender and date of randomisation. IL-6 and D-dimer were measured in stored plasma samples at study entry. Odds ratios were calculated comparing the highest to the lowest quartile for each biomarker.
 
Results: Median levels of biomarkers were elevated in early and late deaths versus controls (3.58 and 3.72 versus 2.14 and 2.33 pg/ml respectively for IL-6; 0.45 and 0.31 versus 0.24 and 0.24 g/ml, respectively for D-dimer). Higher baseline IL-6 levels were associated with both increased early (OR = 5.7, 2.6 - 12.6; P < 0.0001) and late (OR = 5.0, 2.0 - 12.9; P = 0.0007) mortality (p=0.46 for difference between time periods). Similarly, higher D-dimer levels were also associated with increased early (OR = 5.7, 2.6 - 12.8; P < 0.0001) and late (OR = 4.9, 1.6 - 14.5; P = 0.005) mortality (p=0.83 for difference).
 
Conclusions:
HIV-infected patients with elevated D-dimer and IL-6 are at increased risk of death, and this association persists, with minimal attenuation, in long-term follow up. The strength and durability of the association suggest that activation of inflammatory and coagulation pathways play an important role in HIV pathogenesis. Further research to establish the aetiology and to evaluate potential therapeutic interventions is warranted.

conclusion-1.gif

Background-2.gif

mater-3.gif

results-4.gif

rick-5.gif

deaths-6.gif

lane-7.gif