Systemic Inflammation, Coagulation, and Clinical Risk in the START Trial

Area of Science:

• HIV/AIDS research
• Immunology
• Clinical trials

Background:

• The START trial showed immediate antiretroviral therapy (ART) initiation reduces AIDS and serious non-AIDS (SNA) risks.
• Inflammation, coagulation, and vascular injury markers were investigated in relation to clinical outcomes.
• The impact of immediate ART on these biomarkers was also assessed.

Purpose of the Study:

• To investigate the association between inflammation, coagulation, and vascular injury biomarkers and the risk of AIDS, SNA, or death.
• To evaluate the effect of immediate versus deferred ART initiation on these biomarkers.

Main Methods:

• Biomarkers (IL-6, D-dimer) were measured from plasma samples collected before ART initiation and at 8 months.
• Cox regression models analyzed baseline biomarker associations with event risk, adjusted for covariates.
• Analysis of covariance compared biomarker changes between immediate and deferred ART arms.

Main Results:

• Higher baseline levels of IL-6 and D-dimer were independently associated with increased risk of AIDS, SNA, or death (HRs 1.37-1.41).
• These associations persisted after adjusting for CD4+ count, HIV RNA, and other biomarkers.
• Biomarker levels were significantly lower (12%-21%) at 8 months in the immediate ART arm compared to the deferred arm.

Conclusions:

• IL-6 and D-dimer are consistent predictors of clinical risk in HIV-infected individuals across various CD4 counts, regardless of ART status.
• These findings underscore the role of inflammation and coagulation in HIV pathogenesis.
• Further research is needed to develop treatments targeting inflammation beyond ART's effects.