Changes in inflammatory and coagulation biomarkers: a randomized comparison of immediate versus deferred antiretroviral therapy in patients with HIV infection

TY - JOUR

T1 - Changes in inflammatory and coagulation biomarkers: a randomized comparison of immediate versus deferred antiretroviral therapy in patients with HIV infection

AU - Baker, Jason V

AU - Neuhaus, Jacqueline

AU - Duprez, Daniel

AU - Kuller, Lewis H

AU - Tracy, Russell

AU - Belloso, Waldo H

AU - De Wit, Stephane

AU - Drummond, Fraser

AU - Lane, H Clifford

AU - Ledergerber, Bruno

AU - Lundgren, Jens

AU - Nixon, Daniel E

AU - Paton, Nicholas I

AU - Neaton, James D

AU - INSIGHT SMART Study Group

PY - 2011/1/1

Y1 - 2011/1/1

N2 - Objectives: Among a subgroup of participants in the Strategies for Management of Antiretroviral Therapy (SMART) Trial that were naïve to antiretroviral therapy (ART) or off ART (6 months or longer) at study entry, risk of AIDS and serious non-AIDS events were increased for participants who deferred ART compared with those randomized to (re)initiate ART immediately. Our objective was to determine whether ART initiation in this group reduced markers of inflammation and coagulation that have been associated with increased mortality risk in SMART. Changes in these biomarkers have been described after stopping ART, but not after starting ART in SMART. Methods: Stored specimens for 254 participants (126 drug conservation [DC] and 128 viral suppression [VS]) who were naïve to ART or off ART (6 months or longer) were analyzed for interleukin-6, high sensitivity C-reactive protein, and D-dimer at baseline and Months 2 and 6. Results: At Month 6, 62% of the VS group had HIV RNA less than 400 copies/mL and median CD4 count was 190 cells/mm higher than for the DC group (590 versus 400 cells/mm). Compared with DC, the VS group had 32% (95% confidence interval, 19%-43%) lower D-dimer levels at Month 6 (P < 0.001); differences were not significant for high sensitivity C-reactive protein or interleukin-6 levels. Conclusions: In this randomized comparison of immediate versus delayed ART initiation, D-dimer, but not interleukin-6 and high sensitivity C-reactive protein, declined significantly after starting ART. Further studies are needed to determine whether improvements in D-dimer are associated with reduced risk of clinical disease and whether adjunct treatments used in combination with ART can reduce inflammation among individuals with HIV infection.

AB - Objectives: Among a subgroup of participants in the Strategies for Management of Antiretroviral Therapy (SMART) Trial that were naïve to antiretroviral therapy (ART) or off ART (6 months or longer) at study entry, risk of AIDS and serious non-AIDS events were increased for participants who deferred ART compared with those randomized to (re)initiate ART immediately. Our objective was to determine whether ART initiation in this group reduced markers of inflammation and coagulation that have been associated with increased mortality risk in SMART. Changes in these biomarkers have been described after stopping ART, but not after starting ART in SMART. Methods: Stored specimens for 254 participants (126 drug conservation [DC] and 128 viral suppression [VS]) who were naïve to ART or off ART (6 months or longer) were analyzed for interleukin-6, high sensitivity C-reactive protein, and D-dimer at baseline and Months 2 and 6. Results: At Month 6, 62% of the VS group had HIV RNA less than 400 copies/mL and median CD4 count was 190 cells/mm higher than for the DC group (590 versus 400 cells/mm). Compared with DC, the VS group had 32% (95% confidence interval, 19%-43%) lower D-dimer levels at Month 6 (P < 0.001); differences were not significant for high sensitivity C-reactive protein or interleukin-6 levels. Conclusions: In this randomized comparison of immediate versus delayed ART initiation, D-dimer, but not interleukin-6 and high sensitivity C-reactive protein, declined significantly after starting ART. Further studies are needed to determine whether improvements in D-dimer are associated with reduced risk of clinical disease and whether adjunct treatments used in combination with ART can reduce inflammation among individuals with HIV infection.

KW - Adult

KW - Anti-HIV Agents

KW - Biological Markers

KW - Blood Coagulation

KW - C-Reactive Protein

KW - CD4 Lymphocyte Count

KW - Female

KW - Fibrin Fibrinogen Degradation Products

KW - HIV Infections

KW - Humans

KW - Inflammation

KW - Interleukin-6

KW - Male

KW - Middle Aged

KW - Time Factors

KW - Viral Load

U2 - 10.1097/QAI.0b013e3181f7f61a

DO - 10.1097/QAI.0b013e3181f7f61a

M3 - Journal article

SN - 1525-4135

VL - 56

SP - 36

EP - 43

JO - J A I D S

JF - J A I D S

IS - 1

ER -