The Strategies for the Management of AntiRetroviral Therapy
(SMART) trial has transformed HIV research by unambiguously demonstrating the
link between viral replication, inflammation and clinical outcomes. A detailed
sub-study in SMART found that, in adults, particular coagulation and
inflammatory biomarkers (specifically D-dimer and IL-6) were very strongly
associated with mortality risk, and levels of these biomarkers increased in association
with HIV viral load when study participants interrupted ART. In the new issue
of the journal AIDS, a group of Italian researchers describe results of a study
designed to provide insight into whether the findings of SMART are relevant to
children and adolescents with HIV.
The researchers divided a cohort of 88 individuals (mean age
13.5 years) into high and low HIV viral load groups using a cut-off of 1,000
copies of HIV RNA/mL. Higher viral load levels were associated with significantly
lower levels of protein S, a substance involved in blood coagulation; low
levels of protein S are known to be associated with an increased risk of
excessive blood clotting (thrombophilia). Levels of D-dimer were also
significantly elevated in the high viral load group and showed a statistically
significant correlation with HIV RNA levels (R2 0.37, P<0.001). D-dimer is a
small protein fragment that is produced when blood clots are degraded in the body.
Levels of C-reactive protein (CRP), which increased in SMART participants after
ART interruption, showed no differences between the high and low viral load
groups. IL-6 levels were not measured in this study.
In discussing their findings, the researchers state: “The
study, given the low mean age of the cohort, highlights the direct role of HIV
replication on coagulation disorders excluding the possible confounding role of
major known risk factors for thrombosis and CVD, like hypertension, diabetes,
and history of clinical thrombotic event. Furthermore, our analysis took into account
the putative confounding action of other factors associated with an increased
risk of thrombosis and CVD disease both in the general population (smoke, age,
dyslipidaemia), and HIV-infected population (cumulative use of cART and
protease inhibitor, actual use of ABC and ddI, dyslipidaemia). Nevertheless the
study has some limitations since it is a cross-sectional study and the power
for analysis of all variables considered has been limited by the relative small
amount of observations. Prospective studies are needed to confirm and
investigate the clinical implications of our observations.”
AIDS. 24(8):1145-1151, May 15, 2010.
doi: 10.1097/QAD.0b013e328337b9a0
HIV is associated with thrombophilia and high D-dimer in
children and adolescents
Pontrelli, Giuseppe; Martino, Alessandra M; Tchidjou,
Hyppolite K; Citton, Rita; Mora, Nadia; Ravà, Lucilla; Tozzi, Alberto E; Palma,
Paolo; Muraca, Maurizio; Franco, Elisabetta; Rossi, Paolo; Bernardi, Stefania
Abstract:
Background and objective: Atherosclerosis and other
cardiovascular diseases associated with thrombosis appear more relevant and
anticipated in HIV-infected patients after combination antiretroviral therapy
(cART) has reduced AIDS-related diseases and has improved survival. The
association between viral replication and coagulation abnormalities in a cohort
of HIV-infected children and adolescents was investigated here.
Methods: Protein S, protein C anticoagulant and antithrombin
activity, together with fibrinogen, D-dimer, high-sensitive C-reactive protein
and homocysteine were assayed in a cross-sectional study among a cohort of
HIV-infected children and adolescents. Results in patients with high viral load
(HVL, HIV-RNA > 1000 copies/ml) were compared with those in patients with a
lower replication (LVL), adjusting for other demographic, clinical and
therapeutic covariates.
Results: Eighty-eight patients (mean age 13.5 years, CD4
30%, 72% with LVL) were enrolled. A prevalence of protein S and protein C
deficiency of 51 and 8% was, respectively, found. HVL group compared to LVL
showed a significant reduction of protein S, protein C and antithrombin
activities, and an increase of D-dimer levels. The independent association of
HVL with decreased protein S activity (-11.2%, P = 0.04) and increased D-dimer
levels (+0.13 [mu]g/ml, P = 0.004) was confirmed in the multivariate model.
Conclusions: HIV-infected children and adolescents present
high prevalence of thrombophilic abnormalities. The multivariate model
confirmed that high viral replication is independently associated with decrease
of protein S and increase of D-dimer, suggesting the advantage of suppressive
therapy on coagulation homeostasis and the opportunity of an active control of
cardiovascular risk factors starting at a younger age.
Leave a Reply