CROI 2020 Abstract eBook

Abstract eBook

Poster Abstracts

markers were qualitatively higher in HIV+ Heroin+ compared to HIV- Heroin+, only zonulin was statistically higher. Conclusion: IV heroin use is associated with immune activation and altered gut integrity. Although not statistically significant, some markers were higher in HIV+ than HIV- heroin users which may portend higher risk of poor outcomes.

237 LIPID ABNORMALITIES MAY CONTRIBUTE TO ALTERED MACROPHAGE PHENOTYPE IN PEOPLE WITH HIV Emily Bowman 1 , Brian Richardson 2 , Manjusha Kulkarni 1 , Aaren Kettelhut 1 , Janelle Gabriel 1 , Morgan Cichon 1 , Kenneth Riedl 1 , Subha Raman 1 , Susan L. Koletar 1 , Cheryl A. Cameron 2 , Mark Cameron 2 , Nicholas Funderburg 1 1 The Ohio State University, Columbus, OH, USA, 2 Case Western Reserve University, Cleveland, OH, USA Background: HIV infection and antiretroviral therapy (ART) are associated with dyslipidemia and increased cardiovascular disease (CVD) risk. Macrophages accumulate in arterial walls and produce factors that contribute to vascular inflammation. The relationships among lipids and macrophage phenotype in people with HIV (PWH) are unclear. Methods: Coronary artery calcification (CAC) in people with (n=40) and without (n=15) HIV was quantified by computed tomography scanning. PBMCs from HIV+ART+ (n=20) and HIV- donors (n=20) were cultured for 5 days in medium containing 20% autologous serum to generate monocyte derived macrophages (MDMs). Concentration and composition of serum lipids was measured by mass spectrometry. MDM transcriptomes and differential gene expression (DGE) were analyzed using our R Bioconductor pipeline. Foam cell formation was assessed by Bodipy staining. Immune activation was assessed by flow cytometry. Results: PWH (ages 27-67) had significantly increased CAC scores compared to people without HIV (ages 25-70) (CAC=367 v 25, p=0.01). Traditional risk assessments categorize individuals with CAC scores <100 at low risk, and >400 at high risk for CVD events. Older (over 55) PWH (n=17) had an average CAC score of 423, compared to a score of 71 in older people without HIV (n=7). PWH had increased serum levels of free fatty acids (FFAs), with enrichment of saturated fatty acids (SaFAs) and a reduction in polyunsaturated fatty acids (PUFAs). DGE analysis of MDMs from participants with and without HIV identified alterations in immune signaling, DNA damage repair, mitochondrial dysfunction, and lipid processing pathways. Levels of SaFA and PUFA lipid species correlated with unique DGE signatures and altered metabolic pathway activation in MDMs. Bodipy staining indicated greater lipid accumulation. MDMs from PWH also produced more TNFa, IL-6, and ROS, and had increased HLA-DR surface expression. SaFA levels were directly related, whereas PUFAs were inversely related to HLA-DR expression on MDMs from PWH. HIV- MDMs exposed to HIV+ pooled serum displayed greater intracellular lipid accumulation and DGE than cells exposed to HIV- pooled serum. Conclusion: Lipid abnormalities in HIV infection may contribute to a pro-atherogenic MDM phenotype. MDMs from PWH readily form foam cells, have altered transcriptional profiles, and produce mediators of vascular inflammation, which may enhance CVD risk, particularly in the aging HIV population. LIPIDOME ALTERATIONS WITH EXERCISE AMONG PEOPLE WITH AND WITHOUT HIV Emily Bowman 1 , Melissa P. Wilson 2 , Samantha MaWhinney 2 , Catherine M. Jankowski 2 , Nicholas Funderburg 1 , Kristine M. Erlandson 2 1 The Ohio State University, Columbus, OH, USA, 2 University of Colorado, Aurora, CO, USA Background: An increasing burden of age-related comorbidities and impairment of physical function in aging people with HIV (PWH) can be improved, in part, through exercise interventions. The effect of exercise and HIV serostatus on the mechanisms underlying these improvements, such as changes in lipidome composition, is not known. Methods: Sedentary adults (50-75 years old) with (N=24) or without (N=25) HIV participated in supervised endurance/resistance exercise for 24 weeks. In this exploratory secondary analysis of The Exercise for Healthy Aging Study, concentrations of plasma lipids (~1200 lipid species from 13 lipid classes) at 238

236 VALGANCICLOVIR EFFECTS ON GUT AND PULMONARY EPITHELIAL BARRIER MARKERS IN TREATED HIV Sabrina Sevilla 1 , Gabriele B. Beck-Engeser 2 , Vanessa A. York 2 , Rebecca Hoh 2 , Steven G. Deeks 2 , Jeffrey N. Martin 2 , Barbara L. Shacklett 3 , Laurence Huang 2 , Ma Somsouk 2 , Peter W. Hunt 2 1 University of Nevada–Reno, Reno, NV, USA, 2 University of California San Francisco, San Francisco, CA, USA, 3 University of California Davis, Davis, CA, USA Background: The CMV drug valganciclovir broadly suppressed markers of innate and adaptive immune activation in a trial of people living with HIV (PLWH) with incomplete CD4 recovery during antiretroviral therapy (ART). As CMV replicates in and is shed from gut and pulmonary mucosa, we hypothesized that valganciclovir might affect soluble markers of gut and pulmonary epithelial barrier function. Methods: Plasma was assessed from a placebo-controlled trial of valganciclovir (900mg daily for 8 weeks) among 30 HIV/CMV co-infected individuals with incomplete ART-mediated CD4 recovery and high CD8+ T cell activation (>10% CD38+HLA-DR+ CD8+ T cells). Markers of gut barrier dysfunction (sCD14, LPS binding protein [LBP], intestinal fatty acid binding protein [I-FABP], B-D-glucan, and regenerating islet-derived protein-3a [Reg3a]) and pulmonary barrier dysfunction (clara cell secretory protein [CC16], surfactant D), were assessed every 4 weeks. Changes from baseline at each timepoint were compared between arms with linear mixed models, log-transforming variables and normalizing to the baseline interquartile range (IQR) to facilitate comparisons between biomarkers. Results: Among 14 valganciclovir-treated and 16 placebo-treated PLWH, most (93%) were men, 9 (30%) had detectable plasma HIV RNA levels, and median CD4 count was 190 cells/mm 3 . At baseline, there were significant correlations between sCD14 and both I-FABP and B-D-glucan (rho: 0.19-0.21, P<=0.05), but not with other putative measures of gut barrier integrity. Surfactant D appeared to be associated with sTNFR1 (rho: 0.39, P=0.03) and IL-6 (rho: 0.58, P=0.002). In the valganciclovir arm, sCD14 declined by over a quartile from baseline, an effect that persisted for 4 weeks after treatment cessation and was significantly greater than placebo at weeks 4 and 12 (see Table). LBP also appeared to decline by over a quartile in the valganciclovir arm through week 12. Less consistent changes were observed in other markers of gut and pulmonary barrier dysfunction. Conclusion: Treating asymptomatic CMV for 8 weeks in PLWH with incomplete ART-mediated CD4 recovery significantly reduces sCD14 and LBP, without clear effects on more specific markers of microbial translocation and epithelial barrier function. Given high within-subject variability for some of these analytes and the potential for greater effects with longer treatment duration, a longer and larger trial of treating asymptomatic CMV infection is required to definitively test these hypotheses in vivo.

Poster Abstracts

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CROI 2020