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Inflammation Related Morbidity and Mortality Among HIV-Positive Adults: How Extensive Is It?.

Hart, Brian B. BA; Nordell, Anna D. MS; Okulicz, Jason F. MD; Palfreeman, Adrian MD; Horban, Andrzej MD; Kedem, Eynat MD; Neuhaus, Jacqueline MS; Jacobs, David R. Jr PhD; Duprez, Daniel A. MD PhD; Neaton, James D. PhD; for the INSIGHT SMART and ESPRIT Groups
JAIDS Journal of Acquired Immune Deficiency Syndromes: Post Acceptance: October 04, 2017
doi: 10.1097/QAI.0000000000001554
Original Article: PDF Only

Objective: To determine the rate of grade 4, potentially life-threatening, events not attributable to AIDS, cardiovascular disease (CVD) or non-AIDS cancer among participants on antiretroviral therapy (ART), and to describe associations of these events with interleukin-6 and D-dimer.

Design: Cohort study.

Methods: HIV-infected participants on ART (N=3,568) with an HIV RNA level <= 500 copies/mL were followed for grade 4, AIDS, CVD, non-AIDS cancer and all-cause mortality events. Grade 4 events were further classified blinded to biomarker levels as reflecting chronic-inflammation related disease (ChrIRD) or not (non-ChrIRD). Associations of baseline IL-6 and D-dimer with events were studied with Cox models.

Results: Over a median follow-up of 4.3 years, 339 participants developed a grade 4 event (22.9 per 1,000 person years); 165 participants developed a ChrIRD grade 4 event (10.7 per 1,000 person years). Grade 4 events were more common than AIDS (54 participants), CVD (132) and non-AIDS cancer (80) events, any of which developed in 252 participants (17.1 per 1,000 person years). Grade 4 and AIDS events were associated with similar risks of death. Higher IL-6 (hazard ratio=1.19 per doubling of biomarker; p=0.003) and D-dimer (HR=1.23; p<0.001) levels were associated with an increased risk of grade 4 events. IL-6 associations were stronger for ChrIRD (HR=1.38; p<0.001) than non-ChrIRD grade 4 events (HR=1.11; p=0.21).

Conclusions: Morbidity and mortality associated with activation of inflammatory and coagulation pathways include conditions other than AIDS, CVD and non-AIDS cancer events. Effective inflammation-dampening interventions could greatly impact the health of people with HIV.

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