CROI 2020 Abstract eBook

Abstract eBook

Poster Abstracts

(IQR: 20–87). Mean pre-ART viral loads were lower in women than men, 5.2 and 5.6 log 10 copies/mL respectively (P = 0.001). After ART initiation, women more rapidly achieved viral suppression (HIV RNA < 50 copies/mL) than men (age and pre-ART viral load adjusted hazard ratio: 1.33, 95% confidence interval 1.09 - 1.69). They also experienced a faster increase in CD4+ T-cell count and CD4:CD8 ratio during the first two months of treatment. Baseline sex-related differences in CD4+ T-cell counts were more pronounced with increasing age. This led to a sustained mean difference of +99 to +168 CD4+ T-cells/µL depending on age between women and men at 12.5 years of ART. CD4:CD8 ratio of women was persistently higher than that of men by a mean of 0.31. With long-term ART, women and men achieved similar levels of total HIV DNA (mean estimate at the last modelling point: 1.9 log 10 copies/10 6 PBMCs after 70 months of ART for both sexes). Conclusion: ART initiated within 3 months of AHI was associated with a larger immunological benefit in women. This benefit was sustained and more pronounced under very long-term ART, which may give women additional protection from adverse clinical outcomes and premature ageing. 218 PERSISTENT IMMUNE ACTIVATION IN HIV-1–TREATED SUBJECTS COMPARED WITH NON-HIV CONTROLS Sophie Novelli 1 , Camille Lecuroux 1 , Jacques Reynes 2 , Agnes Villemant 3 , Laurent Blum 4 , Asma Essat 1 , Veronique Avettand-Fenoel 5 , Odile Launay 6 , Jean-Michel Molina 7 , Cécile Goujard 8 , Christine Bourgeois 1 , Laurence Meyer 1 1 INSERM, Le Kremlin-Bicetre, France, 2 CHU de Montpellier, Montpellier, France, 3 Hospital Beaujon AP-HP, Clichy, France, 4 Centre Hospitalier René Dubos, Pontoise, France, 5 Necker Hospital, Paris, France, 6 Cochin Hospital, Paris, France, 7 Hôpital Saint-Louis, Paris, France, 8 Hôpital Bicêtre, Le Kremlin-Bicetre, France Background: Non-AIDS events under antiretroviral therapy (ART) are attributed to persistent low-grade inflammation. The magnitude of this inflammation is still discussed, partly because there is no standard value for “basal inflammation”. Here we compared the inflammation profile of HIV- infected patients under long-term suppressive ART to 2 well-characterised HIV-uninfected groups, at low and high risk of HIV acquisition. Methods: HIV participants followed since acute/early HIV infection (AHI) in the ANRS PRIMO cohort were selected if treated for ≥36 months with sustained HIV RNA<50 copies/mL and available frozen samples. Sex and age-matched controls were sampled from the ANRS IPERGAY trial of pre-exposure prophylaxis among men who have sex with men at high risk for HIV infection, and the ANRS COHVAC cohort, a long-term safety cohort of volunteers in preventive HIV-1 vaccine trials. Participants with HBV or HCV infection were excluded. We compared the three groups on plasma levels of ten biomarkers: non-specific markers of inflammation (usCRP, IL6, TNFα, sTNFRII), and markers associated with monocyte activation (sCD14, sCD163, CXCL10), gut epithelial dysfunction (I-FABP, IL17) or fibrosis (hyaluronic acid). We also measured plasma ultrasensitive HIV RNA and total HIV DNA in blood. Analyses were performed separately for men and women. Results: 150 PRIMO subjects (108 men and 42 women) were matched with 141 COHVAC participants (100 men, 41 women) and 102 IPERGAY men. The median age was 47 years. Among PRIMO subjects, 89% had CD4 counts >500 cells/µL and 64% had an undetectable ultrasensitive viral load after a median of 6 years of ART. Smoking and alcohol use were less frequent in COHVAC participants than in the other groups. After adjusting for age, smoking, alcohol use, and body mass index, both HIV-infected men and women had higher levels of sCD14, sCD163, CXCL10, sTNFRII and I-FABP than their non-HIV counterparts. When comparing the two non-HIV groups, IPERGAY men had significantly higher levels of IL17 and TNFα than COHVAC men. Inflammatory levels in HIV subjects were not associated with time since AHI diagnosis, cumulative ART duration, delay of ART initiation, residual viral replication and HIV DNA levels. Conclusion: After a median of 6 years under ART, HIV-infected participants maintained high levels of monocyte activation and gut epithelial dysfunction.

Poster Abstracts

219 SOCS PROTEINS AND JAK-STAT PATHWAY DYSREGULATION IN SIV- INFECTED SUPPRESSED MACAQUES Erandi E. Velarde De La Cruz 1 , Lingyun Wang 1 , Anna Aldovini 1 1 Boston Children's Hospital, Boston, MA, USA Background: Suppressor of cytokine signaling (SOCS) is a family of proteins upregulated rapidly in response to stimulation by Toll-like receptors, cytokines, grow factors and hormones that provide a negative feedback to the stimulation that triggered them by inhibiting the JAK-STAT signaling pathway. SOCS proteins, in particular SOCS3, have also been described as having a central role in metabolic syndrome, diabetes and atherosclerosis. In vivo data for SOCS levels in HIV-infected patients are very limited. Methods: Using intracellular staining (ICS) and flow cytometric analyses, we evaluated the expression kinetics of SOCS1 and SOCS3 proteins and their activity by measuring the percentages and the accumulation level, estimated via MFI, of SOCS1, SOCS3, TLRs, IFNs and other JAK-STAT signaling pathway-related proteins in individual subpopulations of blood and lymph node MNC, harvested at day 0, peak of infection, and week 20, and 60 from SIV-infected Rhesus macaques left untreated, treated with ART or ART+p38MAPK inhibitor. Boolean data analysis permitted the evaluation of co-expression of the above proteins. Results: In the context of untreated or treated chronic HIV or SIV infection, a persistent but aberrant activation of SOCS proteins and their targets is an important feature of the dysfunctional TLR-IFN-SOCS pathway. The percentage of SOCS+ cells remains higher than at peak viremia after 54-59 weeks of ART despite virus suppression and its expression does not correlate with viral loads. SOCS1 and SOCS3 expression is elevated in virtually all mononuclear cell subpopulations yet the inhibition of their targets JAK and STAT is not complete and markers of innate immunity that should be impacted by SOCS activity remain elevated. Conclusion: Persistent SOCS protein expression during suppressed SIV infection supports the existence of additional stimulation that maintains their expression and/or dysregulation of their negative feedback. Incomplete JAK-STAT pathway suppression by SOCS proteins is consistent with residual activation of innate immunity pathways and dysregulation of antiviral immunity. Given the association of their expression with metabolic conditions, SOCS protein chronic activation could be also relevant to the metabolic complications observed in ART patients. 220 EFFECT OF HIV SUPPRESSION ON CYTOKINES IN BLOOD AND SEMINAL PLASMA Stephen A. Rawlings 1 , Felix Torres 1 , Andrea Lisco 2 , Leonid Margolis 2 , Sara Gianella 1 , Christophe Vanpouille 2 1 University of California San Diego, La Jolla, CA, USA, 2 NIH, Bethesda, MD, USA Background: HIV infection disrupts the cytokine network and it remains disrupted after HIV is suppressed by ART. Characterization of this continuing disruption in genital secretions is important for understanding the mechanisms of HIV sexual transmission. Therefore, we undertook to determine the cytokine

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CROI 2020