CROI 2016 Abstract eBook

Abstract Listing

Poster Abstracts

False Discovery Rate-­‐Adjusted P-­‐value

Number of Genes or CpG Sites

Module Pathways Identified 201 Gene Expression Lysosome, Immune Response, Plasma Membrane 554 Gene Expression Immune Response, Defense Response, Inflammatory Response, Response to Wounding 791 Gene Expression Cilia 6050 Gene Expression Intracellular Organelle, Membrane-­‐Enclosed Lumen 43 Gene Expression None Identified 452 Gene Expression Cell to Cell Signaling, Cell Membrane 365 Gene Expression Oxidation/Reduction, Microsomes 427 Gene Expression Immune Response, Immunoglobulion, Antigen Presentation 1274 Gene Expression Glycoprotein, Plasma Membrane, Immune Response 5675 Gene Expression Nucleus, Transcription Regulation, Nuclear Lumen 5861 Gene Expression Olfactory Transduction Green Yellow 245 Gene Expression Immunoglobulin, Antigen Processing and Presentation 63 Gene Expression None Identified Methylation Blood Vessel Development, Embryonic Development Methylation Membrane Fraction, Plasma Membrane, Cell Fraction Methylation None Identified Methylation Regulation of Metabolic Process, Skeletal Development, Cell Migration Midnight Blue 82 Gene Expression Magnesium Ion Binding Methylation None Identified Methylation ATP-binding Methylation Pleckstrin Homology, Plasma Membrane, Cellular Morphogenesis Methylation Lung Development, Respiratory Tube Development 26951 Methylation Transcription Regulation, Embryonic Morphogenesis 20139 Methylation Plasma Membrane, Cell Adhesion, Glycoprotein Analysis Tan Red Green Turquoise Dark Green Black Magenta Pink Brown Blue Grey Light Green Magenta Orange White Cyan Salmon Black Turquoise Blue Brown 2202 266 176 1307 1403 3114 4575 Saddlebrown 163

5.0x10-4 1.0x10-12

0.05

2x10-4 2x10-7

N/A

1.0x10-5 2.0x10-2 1.0x10-3 1.0x10-6 2x10-4 4.9x10-42

1x10-4

N/A

1x10-2

0.1 0.1

1x10-2

0.1 0.1

1x10-2

1.0x10-2 1x10-2 1x10-8

726 Immunological Signaling During HSV-2 and CMV Vaginal Reactivation at ART Initiation

Andrew D. Redd 1 ; Eshan U. Patel 2 ; Allison R. Kirkpatrick 3 ; Aaron A.Tobian 4 ; Sara Gianella 5 ; Sarah Kalibbala 6 ;Thomas C. Quinn 4 ; David Serwadda 7 ; Steven J. Reynolds 2 ; Martha Nason 1 1 NIAID, NIH, Bethesda, MD, USA; 2 NIH, Bethesda, MD, USA; 3 NIAID, NIH, Baltimore, MD, USA; 4 Johns Hopkins Univ Sch of Med, Baltimore, MD, USA; 5 Univ of California San Diego, San Diego, CA, USA; 6 Rakai Hlth Scis Prog, Rakai, Uganda; 7 Makerere Univ Schoool of PH, Kampala, Uganda Background: Vaginal shedding of herpes simplex virus type 2 (HSV-2) and cytomegalovirus (CMV) was increased in HIV-infected women within the first three to four months after antiretroviral therapy (ART) initiation. The role of vaginal pro-inflammatory cytokine expression on herpetic reactivation was examined in these same women. Methods: HIV and HSV-2 co-infected individuals with a CD4 cell count between 300 and 400 cells/μl were enrolled in a double-blind, randomized placebo-controlled trial of HSV-2 suppression with acyclovir. Participants were randomly assigned to receive placebo or 400mg acyclovir twice daily for 24 months. Self-collected vaginal swab samples fromwomen previously tested for HSV-2 and CMV shedding taken one month prior (-1), at time of ART initiation (0), and months 1, 2, 3, 4 & 6 after ART initiation were screened for presence of pro-inflammatory cytokines IL-1β, -2, -4, -6, -8, -10, -12p70, -13, TNF-α, and IFN-γ (Meso Scale Discovery Inc, Rockville, MD). Cytokines were dichotomized by median value and associations with HSV-2 and CMV shedding were evaluated after adjusting for month of sample collection and ART status. Relationships between cytokine levels and HSV-2 or CMV shedding over time were modeled using Generalized Estimating Equations (GEE). A Poisson model with a log link and robust standard errors was used. Relationships between cytokine levels and shedding were visualized with heat maps using geometric means of cytokine levels. Results: The median values for vaginal IL-1β, IL-2, IL-4, IL-10 and TNF-α were 0 pg/mL; the other medians included IL-6 median=2.95 pg/mL; IL-13 median=9.9 pg/mL; IL-8 median=1,137 pg/mL. Presence of HSV-2 DNA shedding was significantly associated with higher IL-6 (p=0.003) and TNF-α (p=0.010), whereas CMV DNA shedding was associated with higher IL-1β (p=0.015), IL-2 (p=0.007), and IL-6 (p=0.006). For HSV-2 and CMV, women were divided according to shedding status pre- (-1 and 0 months) and post-ART (months 1-4). Women who shed HSV-2 post-ART appeared to have a pattern of higher pro-inflammatory cytokine levels (IL-2, -6, -8 -13, -10, and TNF- α) after HAART initiation (Figure). Figure : Heat maps of cytokine levels for women who did not shed HSV-2 compared to women who did shed post-ART only. Conclusions: The association of HSV-2 and CMV shedding with higher IL-6 levels suggests that herpetic reactivation in the genital tract of African women may be an immune restoration inflammatory syndrome-like event.

Poster Abstracts

727

Longitudinal Viral Dynamics in Semen of HIV+Men Before and After Early ART Sheldon R. Morris; Davey M. Smith; MilenkaVargas; Susan J. Little; Sara Gianella Univ of California San Diego, San Diego, CA, USA Background: Multiple viruses co-infect the male genital tract and most likely influence each other’s replication. The longitudinal replication dynamics of HIV and human herpesviruses (HHV) before and after starting early antiretroviral therapy (ART) have not been systematically described.

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CROI 2016