CROI 2020 Abstract eBook

Abstract eBook

Poster Abstracts

1.19 – 1.67], p<10-4) and positive HCV serology (OR 1.45 [95% CI, 1.20 – 1.76], p<10-4) were significantly associated with higher risk of psoriasis. To be born in West and Central Africa (OR 0.15 [95% CI, 0.10 – 0.25], p<10-4), in the Caribbean islands (OR 0.14 [95% CI, 0.05 – 0.45], p=0.0008) and in Latin America (OR 0.31 [95% CI, 0.14 – 0.69], p=0.004) was associated with lower risk of psoriasis compared to patients born in mainland France. Psoriasis preceded HIV diagnosis in 115 patients (19.6%), was concomitant in 119 patients (20.3%), and developed more than one year after in 352 patients (60.1%). For 114 patients (16.3%), the chronology was unknown. Patients in whom psoriasis preceded HIV diagnosis were significantly more often HLA-B*57:01 positive than the patients in whom the psoriasis was concomitant or occurred after HIV diagnosis. Conclusion: PLHIV carrying HLA-B*57 01 have around 3-fold risk of psoriasis. Such association might provide a possible explanation for the observed differences in psoriasis prevalence between ethnic groups. 714 IMPACT OF ANTIRETROVIRAL THERAPY INITIATION ON EPIGENETIC AGING AND TELOMERE LENGTH Clinical: (M) Other Complications of HIV Infection and Antiretroviral Therapy Andrés Esteban-Cantos 1 , Javier Rodríguez-Centeno 1 , Pilar Barruz 1 , Francisco Gayá 1 , Julián Nevado 1 , Belen Alejos 2 , Natalia Stella-Ascariz 1 , Rocio Montejano 1 , Jose I. Bernardino 1 , Eric Florence 3 , Lars Mathiesen 4 , Rosa de Miguel 1 , Francisco Arnalich 1 , Fiona Mulcahy 5 , Denes Bánhegy 1 , Cédrick Wallet 6 , François Raffi 7 , Berta Rodes 1 , Jose R. Arribas 1 1 Hospital La Paz Institute for Health Research, Madrid, Spain, 2 Institute of Health Carlos III, Madrid, Spain, 3 Institute of Tropical Medicine, Antwerp, Belgium, 4 Copenhagen University Hospital, Copenhagen, Denmark, 5 St. James's Hospital, Dublin, Ireland, 6 CHU de Bordeaux, Bordeaux, France, 7 CHU de Nantes, Nantes, France Background: Epigenetic age (EA) is an accurate predictor of biological age based on changes in DNA methylation. We investigated how changes in T cell subtypes after antiretroviral therapy (ART) initiation impact on EA, epigenetic age acceleration (EAA) and blood telomere length (TL). Methods: We analyzed 114 randomly selected participants in the NEAT001/ ANRS143 clinical trial before and 96 weeks (W96) after initial ART introduction. Whole blood DNA methylation profiles were assayed via Illumina Infinium MethylationEPIC BeadChips. Data were preprocessed using Noob normalization. The EA and estimated abundance of leukocyte subsets were obtained from the advanced analysis for blood tissue using the Horvath´s DNA methylation Age Calculator. We estimated three EAA measures: universal (AgeAccel), extrinsic (EEAA) and intrinsic (IEAA). We measured telomere length (TL) with multiplex qPCR. Results: At baseline (BL), male: 88%, mean chronological age: 39.2 years, Caucasian: 80%, HIV-1 RNA: 4.7 log 10 c/ml, and mean CD4+ and CD8+ (flow cytometry): 311 and 954 cells/µl. At W96, 96% had HIV-RNA <50 c/ml and mean CD4+ and CD8+ were 564 and 845 cells/µl. At BL, EA positively correlated with chronological age (rho: 0.891, p<0.001) while TL correlated negatively (rho: -0.490; p<0.001). Mean EA at BL and W96 was 47.5 and 47.6 years respectively. Age advancement (EA minus chronological age) significantly improved after ART initiation (BL: 8.3 vs W96: 6.5 years, p=0.007). Compared with BL, two measures of mean EAA slowed at W96 (AgeAccel: -1.49 years, p=0.011; EEAA: -4.02 years, p<0.001), while IEAA did not change (0.03 years, ns). EAA decreased in 71.05% (AgeAccel) and 78.07% (EEAA) of participants. At W96, EA correlated negatively with CD4+/CD8+ ratio by flow cytometry, estimated CD4+, naïve CD4+ and naïve CD8+, and positively with estimated CD8+CD28-CD45RA- T cells and NKs. Mean TL change at W96 was 0.034 (T/S). At W96 TL correlated positively with CD4+/CD8+ ratio by flow cytometry, estimated abundance of total CD4+, naïve CD4+ and naïve CD8+ and negatively with estimated abundance of CD8+CD28-CD45RA- and NKs (Table). Conclusion: EA stabilized and EAA slowed in the majority of patients after starting ART. However, an age advancement of 6.5 years persisted after the first two years of successful ART. The reversal of epigenetic aging and the increase in blood TL caused by ART initiation are likely driven by changes in T cell subtypes toward less differentiated phenotypes.

715 IN VITRO IMPACT OF TAF ON MITOCHONDRIAL FUNCTION IN IMMUNE CELLS

Eleni Ritou 1 , Rachel Heymans 1 , Theodoros Kelesidis 1 1 University of California Los Angeles, Los Angeles, CA, USA

Background: Mitochondrial dysfunction has been involved in toxicity of antiretrovirals such as Zalcitabine (ddC). Markedly lower plasma levels of tenofovir (TFV) are thought to lead to the more favorable bone and renal safety profile of tenofovir alafenamide (TAF) compared to tenofovir disoproxil fumarate (TDF). It is unknown whether an increase in intracellular levels of the active metabolite, tenofovir-diphosphate (TFV-DP) with TAF (compared to TDF) may alter mitochondria. This study was designed to address whether TAF affects in vitro mitochondrial membrane potential (MMP), a direct measure of the state of energization of the mitochondria, in peripheral blood mononuclear cells (PBMCs). Methods: PBMCs were isolated from healthy 18-40 years old participants (n=10). PBMCs were incubated for 2-hour with TDF and/or TAF at concentrations that model clinically relevant plasma exposure. ddC was used as positive control. We used flow cytometry and the dye Tetramethylrhodamine ethyl ester (TMRE) to quantify the MMP in immune cells. Wilcoxon tests were used for statistical comparison between groups. Results: After 2 hours of in vitro exposure of PBMCs to 0.12-3.3 µM TAF, TDF and ddC, 3.3 µM ddC and 0.12, 3.3 µM TDF did not affect the median fluorescence intensity (MFI) of TMRE in CD3+, CD4+, CD8+ T cells and CD14+ cells compared to DMSO control. 3.3 µM TAF increased the MFI of TMRE in CD3+ T cells and in CD14+monocytes compared to DMSO control (p<0.05). 3.3 µM TAF increased the MFI of TMRE in CD8+ T cells compared to ddC (p<0.05). 2 hours of in vitro exposure of primary PBMCs to 0.12-3.3 µM TAF did not affect the MFI of TMRE in CD4+ T cells and increased the MFI of TMRE compared to TDF in CD3+ T cells and CD14+monocytes (Figure). Conclusion: We did not find any evidence of in vitro mitochondrial toxicity (reduction in MMP) with TAF. TAF may increase in vitro the MMP in resting PBMC as early as 2 hours. This concentration dependent effect was more prominent in monocytes compared to T cells. The clinical relevance of these in vitro findings is unknown. The effect of TAF on mitochondrial function in chronic treated HIV should be further explored in patients switching from TDF to TAF regimens.

Poster Abstracts

CROI 2020 262