CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

Conclusions: Pre-ART inflammation/coagulation activation do not predict CD4 response to ART and appear to influence the risk of clinical outcomes through mechanisms other than by blunting long-term CD4 gain. 316 Plasma Levels of sCD163 Predict All-Cause Mortality FromHIV Infection Troels Bygum Knudsen 1 ; Janne Petersen 2 ; Holger Jon Møller 3 ; Søren Moestrup 4 ; Jesper Eugen-Olsen 2 ; Gitte Kronborg 1 ;Thomas Benfield 1 1 Copenhagen University Hospitals, Hvidovre, Copenhagen, Denmark; 2 Copenhagen University Hospitals, Hvidovre, Copenhagen, Denmark; 3 Aarhus University Hospital, Aarhus, Denmark; 4 Aarhus University, Aarhus, Denmark Background: CD163, a monocyte- and macrophage-specific scavenger receptor, is shed from the cell surface as soluble CD163 (sCD163) during activation. Monocyte/macrophage activation may contribute to on-going low-grade inflammation in human immunodeficiency virus (HIV)-infected patients. We therefore investigated the role of monocyte activation by measuring sCD163 levels in relation to outcome from HIV infection. Methods: Plasma sCD163 levels were measured in 794 individuals with HIV infection in 2004/5. The prognostic value of sCD163 was evaluated by Cox proportional hazards regression analysis after adjustment for other risk factors. Kaplan-Meier survival curves were constructed for 0-30, 31-60, 61-90 and 91-100 percentiles. All values are median and interquartile range. Results: Individuals were 42 (IQR: 37-50) years old and 72%were male. 43%were men who had sex with men (MSM), 36%were heterosexuals (HSX) and 15% injection drug users (IDU). 86%were receiving antiretroviral treatment (ART). Baseline CD4 T cell count was 502 (348-705) per m l and HIV RNA <20 (<20-87) copies/mL. Plasma sCD163 was 3.39 (2.27- 5.07) mg/L. During 8.4 (8.1-8.8) years of follow up, there were 67 deaths (8.4%). Individuals who died had significantly higher sCD163 levels than survivors. In adjusted analysis, the mortality increase per mg of sCD163 was 8% (Hazard rate (HR): 1.08, 95% confidence interval (CI): 1.05-1.12). Age (HR: 1.07 (95% CI: 1.05-1.10) per year increment) and IDU vs. no IDU (HR: 2.30 (95% CI: 1.27-4.15) were other independent predictors of death while higher CD4 T cell counts (HR: 0.18 (95% CI: 0.09-0.37) per log increment) were associated with a decreased risk of death. In time-updated analysis, ART did not affect outcome (HR: 1.32 (0.59-2.95). The top 10% group of sCD163 had a 5-fold increased risk of death compared to the lowest 30% group (HR: 5.75 (95% CI: 2.20-15.02) (Figure 1).

Poster Abstracts

Conclusions: The study verifies a clear association between the scavenger receptor system of macrophages and survival in HIV-infected individuals suggested by previous studies. It is the first to demonstrate a highly significant increase in mortality among HIV-infected individuals with an excessive activation of their monocyte/macrophage system. Our findings show that sCD163 is a novel prognostic marker and suggest that monitoring monocyte/macrophage activation may be important in HIV infection. 317 Immunologic Pathways That Predict Mortality in HIV+ Ugandans Initiating ART Sulggi A. Lee 1 ; Helen Byakwaga 2 ;Yap Boum 2 ;Tricia Burdo 3 ;Yong Huang 1 ; Jessica Haberer 5 ; Annet Kembabazi 2 ; David R. Bangsberg 5 ; Jeffrey Martin 1 ; PeterW. Hunt 1 1 University of California San Francisco, San Francisco, CA, US; 2 Mbarara University of Science and Technology, Mbarara, Uganda; 3 Boston College, Boston, MA, US; 4 University of California San Francisco, San Francisco, CA, US; 5 Massachusetts General Hospital and Harvard University, Boston, MA, US Background: Abnormal immune activation persists in most HIV-infected individuals despite prolonged antiretroviral therapy (ART)-mediated viral suppression, and predicts increased morbidity and mortality, but the specific immunologic pathways predicting disease remain incompletely defined, particularly in resource-limited settings. Plasma kynurenine/tryptophan (KT) ratio, a marker of indoleamine 2,3-dioxygenase-1 (IDO) activity, strongly predicts mortality in this setting, but whether it is simply a marker for other immunologic pathways is unclear. Methods: We sampled the first 542 HIV-infected Ugandans initiating ART in the UARTO cohort and measured plasma KT ratio, D-dimer, IL-6, sCD163, sCD14, and T cell activation (%HLA-DR+CD38+) at baseline and month 6 of ART-mediated viral suppression (<400 copies/ml). Predictors of mortality were assessed with Cox proportional hazards models, adjusted for age, body mass index, and pre-ART CD4+T cell count. Results: Participants were mostly female (70%) with a median age of 34, and had advanced disease (median baseline CD4+ count 140 cells/mm 3 and HIV RNA 5.0 log 10 copies/ mL) at ART initiation. A total of 43 deaths occurred during a median 7 years of follow-up, with just 10% LTFU at 7 years. As previously reported, both pre-ART and month 6 KT ratio predicted increased mortality. In addition, pre-ART D-dimer, IL-6, and sCD14 were associated with increased mortality in unadjusted and adjusted models. After 6 months of ART- mediated suppression, IL-6 and sCD14 remained significant predictors of mortality, but CD4+ and CD8+ T cell activation were associated with even greater risks of death. However,

255

CROI 2015