CROI 2020 Abstract eBook

Abstract eBook

Poster Abstracts

were higher in the deferred compared to immediate group. Follow-up continues in START to determine the clinical consequences of excess inflammation from delayed diagnosis and treatment

Reserve University, Cleveland, OH, USA, 5 University of California San Diego, La Jolla, CA, USA Background: Despite antiretroviral therapy (ART), individuals with HIV maintain an HIV reservoir with high levels of systemic inflammation and are more likely to have non-AIDs-defining events compared to those without HIV. We performed a case-control study of AIDS Clinical Trials Group (ACTG) participants to assess the relationship of HIV reservoir size with levels of systemic inflammation, viral co-infections, and risk of non-AIDS-defining events. Methods: Participants were ART-naïve at the time of enrollment, maintained plasma HIV-1 RNA levels <400 copies/mL after ART initiation, and were part of a long-term ACTG follow-up cohort. Cases were defined as participants who had a non-AIDS-related event (MI, stroke, non-AIDS-defining malignancy, serious bacterial infection, or death from a non-AIDS-defining event). Controls were identified and matched based on age, sex, baseline CD4+ T-cell count, and ART regimen. PBMCs and plasma specimens were collected at both 1 year after ART initiation and at the pre-event time point, and analyzed for levels of IL-6, sCD14, interferon γ (IFN-γ), inducible protein 10 (IP10), sTNFR-I, sTNFR-II, D-dimer, CMV and EBV DNA and antibody levels. T-cell phenotyping was performed by flow cytometry. Total HIV DNA levels in PBMCs were measured by qPCR. Adjusted and unadjusted conditional logistic regression analyses were performed to determine if HIV DNA levels predicted the occurrence of non-AIDS-defining events. Results: Samples from 102 cases and 201 controls at year 1 and from 65 cases and 110 controls pre-event were included. Total HIV DNA levels at either 1 year after ART initiation or pre-event were not predictive of non-AIDS-defining events in either unadjusted models or models adjusted for baseline viral load, immune status, or other co-morbidities. One year after ART initiation, there were modest associations between levels of HIV DNA and CMV IgG (Spearman r=0.20, p=0.01), EBV DNA (r=0.14, p=0.05), IL-6 (r=0.18, p=0.01), D-dimer (r=0.22, p<0.01), sCD14 (r=0.18, p=0.01), and sTNFR-I (r=0.15, p=0.03). Conclusion: The size of the HIV reservoir, as reflected by the levels of total HIV DNA, was not predictive of non-AIDs-defining events. The associations of HIV reservoir size with EBV/CMV co-infections and inflammatory markers suggest potential interactions between host immune responses and HIV persistence. Carlee Moser 1 , Peter W. Hunt 2 , Martin Hoenigl 3 , Ashley McKhann 1 , Christophe Vanpouille 4 , Alan Landay 5 , Nicholas Funderburg 6 , Michael M. Lederman 7 , Ronald Bosch 1 , Sara Gianella 3 1 Harvard T.H. Chan School of Public Health, Boston, MA, USA, 2 University of California San Francisco, San Francisco, CA, USA, 3 University of California San Diego, San Diego, CA, USA, 4 National Institute of Child Health and Human Development, Bethesda, MD, USA, 5 Rush University Medical Center, Chicago, IL, USA, 6 The Ohio State University, Columbus, OH, USA, 7 Case Western Reserve University, Cleveland, OH, USA Background: Improvements in technology (new assays, multiplex panels) and large repositories of clinical samples accelerate investigations of numerous individual biomarkers with potential for increased risk of type 1 error. Approaches to combine biomarkers can gain biological understanding and improve statistical efficiency to assess risk of clinical events; however, the best high-dimensional analytic methods are not clear. Methods: Seventeen biomarkers measured at year 1 of suppressive ART were analyzed, from an ACTG case-control study of predictors of subsequent non-AIDS clinical events (141 cases and 310 matched controls). A targeted subset of 10 biomarkers of monocyte and macrophage activation was pre-specified, which we hypothesized to be most predictive of cardiovascular events. Three statistical approaches were considered for data reduction: 1) simple, equally weighted average of all cytokines, 2) optimally weighted combination of targeted cytokines from confirmatory factor analysis, 3) optimally weighted combination of all cytokines from principal components analysis (PCA). Cytokines were log-transformed and normalized (mean 0, SD 1) prior to analysis. Scores from each method were analyzed in conditional logistic regression models to evaluate risk of subsequent non-AIDS events. Results: The best analytical approach was PCA, as principle component (PC) scores had reduced variability when included in regression models compared to other approaches. Based on scree plots and other diagnostics, selecting 2 PCs described the data best, compared to 1 or 3 PCs. The 2 PCs were primarily

241 NON-AIDS—DEFINING EVENTS IN HIV CONTROLLERS VS ART- CONTROLLED PATIENTS Carmelite Audrey Manto Kuidjo 1 , Alicia Castro Gordon 2 , Cécile Goujard 2 , Laurence Meyer 2 , Olivier Lambotte 2 , Asma Essat 1 , Arnoo Shaiykova 1 , Faroudy Boufassa 1 , Nicolas Noel 2 , for the ANRS CO21 CODEX and CO6 PRIMO Study Groups 1 INSERM, Le Kremlin-Bicetre, France, 2 AP–HP, Paris, France Background: HIV controllers (HICs) are rare persons living with HIV who spontaneously maintain low or undetectable viremia. Low-grade chronic inflammation persisting in this population could lead to higher rates of non-AIDS defining events (nADEs) than in patients who achieve low or undetectable viremia on antiretroviral therapy (ART). Methods: From the ongoing multicenter ANRS CODEX cohort, we enrolled 315 HICs with a known HIV-1 infection ≥5 years, with at least 5 consecutive viral loads (VL) below 400 HIV RNA copies/mL in the absence of ART. The ongoing multicenter ANRS PRIMO Cohort enrolls HIV-1 infected patients diagnosed during primary infection (≤3 months). From this latter cohort, we included 328 patients who initiated ART ≤1 month after the diagnosis, with undetectable VL ≤12 months following ART initiation and for at least 5 years (“ART-subjects”). Incidence rates (IR) of first nADEs, i.e. malignancies, cardiovascular, pulmonary, hepatic, psychiatric or bone events were compared between HICs and ART- subjects; potential determinants were assessed by using Cox regression models. Results: The most common events observed in the 2 cohorts were non-AIDS related infections (36.9%), psychiatric (17.2%), cardiovascular (6.8%), and malignancies (6.1%), with no statistically significant differences in distribution between the 2 cohorts. Two and 4 non-AIDS related deaths were observed among HICs and ART subjects, respectively. All-cause nADEs incidence rates were 2.8 per 100 person-years (py) and 5.3 per 100 py among HICs and ART subjects, respectively (Hazards Ratio HR=0.53 [95%Confidence Interval (95%CI), 0.40-0.71]. After adjustment for the cohort, demographic and immunological characteristics, the only other factor associated with all cause nADEs occurrence was age 36-43 (vs. 18-29) years at beginning of control (HR=1.56 [95%CI, 1.06-2.30]). Baseline CD4 T-cell count or nadir, CD4/CD8 ratio, history of viral blips, HBV/HCV co-infection and tobacco use, were not associated with an increased risk of nADEs. Conclusion: HICs, defined on the basis of ≥5-year period of spontaneous viral control, experienced two times less nADEs than virologically suppressed patients on ART. Age was the only other factor independently associated with nADEs occurrence, irrespective of immune or virologic parameters. These results do not argue in favor of expanding the indication for ART for HICs subjects but rather a case-by-case approach considering clinical outcomes such as nADEs besides immune activation. 242 TOTAL HIV DNA LEVELS DO NOT PREDICT NON-AIDS-DEFINING EVENTS Colline Wong 1 , Ashley McKhann 2 , Carlee Moser 2 , Alan Landay 3 , Michael M. Lederman 4 , Sara Gianella 5 , Jonathan Z. Li 1 1 Brigham and Women's Hospital, Boston, MA, USA, 2 Harvard T.H. Chan School of Public Health, Boston, MA, USA, 3 Rush University, Chicago, IL, USA, 4 Case Western

Poster Abstracts

243 PRINCIPAL COMPONENTS ANALYSIS TO IDENTIFY BIOMARKERS PREDICTIVE OF NON-AIDS EVENTS

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CROI 2020