CROI 2016 Abstract eBook

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duplicate. Experiments for each antiretroviral were repeated at least 5 times with PBMCs from different donors. Statistical significance was calculated using Wilcoxon signed rank test. Results: TFV and ABC induced a significant dose-dependent decrease of telomerase activity within the therapeutic dose range in vivo (Fig A). Inhibition induced by TFV at 0.5 µM and 1 µM was median [(IQR), (min-max)] 29% [(29%-34%), (12%-39%)], p =0.042 and 28 [(28%-41%), (25%-47%)], p =0.042. For ABC at 3 μM and 10 μM inhibition was 12 [(9%-13%), (8%-17%)], p =0.043 and 14 [(10%-29%), (7%-40%)], p =0.043. We did not detect changes in levels of hTERT protein (Fig B) or in expression of hTERT (Fig C) and other telomerase genes (not shown). Exposure to FTC or DRV did not affect telomerase activity, levels of hTERT protein or mRNA levels of telomerase genes (Fig A, B, C). Conclusions: Our results suggest that TFV and ABC but not FTC or DRV, inhibit telomerase activity within the therapeutic range. This inhibition does not involve changes in expression levels of telomerase genes or hTERT protein. The in vivo relevance of these findings remains to be elucidated.

670 Risk Factors of Short Telomere Length and Decreased Mitochondrial DNA in HIV Patients Rumi Minami ; SoichiroTakahama;Yu Kaku; MasahiroYamamoto Natl Hosp Org, Kyushu Med Cntr, Fukuoka, Japan

Background: Premature aging is one of the important issues in HIV/AIDS. Telomere length (TL) shortening and alterations of mitochondrial biogenesis are recognized as markers of cellular aging. In this study, we measured the leukocyte TL and mitochondrial DNA copy number to nuclear DNA (mtDNA) in combination antiretroviral therapy (cART) treated HIV patients and uninfected healthy controls. We investigated the association between TL and mtDNA, and examined which clinical parameters determined TL and mtDNA in young and middle-aged HIV patients. Methods: Three hundred and fifty-five HIV patients on cART for > 6 months, and 141 HIV-uninfected controls were enrolled. Relative TL and mtDNA in leukocytes were estimated by quantitative real-time polymerase chain reaction. Linear regression analysis was used to determine the factors that associate with TL and mtDNA. We assessed several variables associated with HIV infection (CD4, HIV-RNA before cART), cART (duration, regimen), and other factors (age, smoking, BMI, hypertension, HOMA-IR, etc.). Variables found to be important in univariate analysis were multivariate model candidates. Results: Of 355 HIV patients, 182 were aged less than 40 (young), and 173 were aged over 40 (middle-aged). Of 141 HIV uninfected controls, 64 were young and 77 were middle aged. In HIV patients, TL was significantly shorter and the rate of decline by age was greater than in controls. mtDNA also decreased significantly in HIV patients than in controls. TL was positively associated with mtDNA in young (r=0.441, p<0.0001) and middle-aged HIV patients (r=0.232, p=0.0022), but in controls, positive correlation was seen only in the middle aged (r=0.248, p=0.03). Multiple linear regression analysis showed that in young patients, nucleoside reverse transcriptase inhibitor (NRTI) use was independent factor of short TL (p=0.013) and decreased mtDNA(p=0.02). On the other hand, in middle-aged patients, protease inhibitor (PI) use (p=0.035) as well as NRTI use (P<0.0001) was independent factor of short TL. Other clinical parameters were not significantly related to TL and mtDNA. Conclusions: In patients with cART, TL and mtDNA was positively correlated in young and middle-aged generation. NRTI use was a common risk factor of short TL and decreased mtDNA. In middle-aged patients, PI use was also risk factor of decreased mtDNA. To minimize the premature aging of HIV patients, we must optimize the cART. NRTI or PI sparing regimen is one of the candidates, especially in middle-aged patients. 671 CRP, D-dimer, and Oxidized LDL Predict Myocardial Infarction in Treated HIV Infection Peter W. Hunt 1 ; Heidi M. Crane 2 ; Daniel Drozd 2 ; Michelle Floris-Moore 3 ; Richard Moore 4 ; Mari M. Kitahata 2 ; Michael S. Saag 5 ; Michael M. Lederman 6 ; Jeffrey N. Martin 1 ; for the CFAR Network of Integrated Clinical Systems (CNICS) 1 Univ of California San Francisco, San Francisco, CA, USA; 2 Univ of Washington, Seattle, WA, USA; 3 Univ of North Carolina at Chapel Hill, Chapel Hill, NC, USA; 4 Johns Hopkins Univ, Baltimore, MD, USA; 5 Univ of Alabama at Birmingham, Birmingham, AL, USA; 6 Case Western Reserve Univ, Cleveland, OH, USA Background: The immunologic pathways that increase myocardial infarction (MI) risk in HIV-infected individuals on suppressive antiretroviral therapy (ART) and the specific role of oxidized low-density lipoprotein (oxLDL) in this process remain unclear. Methods: HIV-infected cases with ART-mediated viral suppression (<400 copies/ml) who developed a confirmed Type 1 MI (plaque rupture/thrombosis) within the subsequent 3 years of an available plasma specimen were sampled from CNICS (an 8 site practice-based network) from 2001-2012. Each MI case was matched using density sampling to ≤3 controls by calendar time, age, gender, race, duration of viral suppression, and CD4 count. Associations between plasma biomarkers and subsequent MI were assessed by conditional logistic regression. Biomarkers associated with MI in unadjusted models (P<0.10) were assessed in adjusted models to assess independence. Results: A total of 51 ART-suppressed cases with subsequent Type 1 MI and 122 matched controls were selected. Among all participants, 78%were men, 56%were non-white race, and median values were: age, 50 years; duration of viral suppression, 36 months; and CD4 count, 574 cells/mm 3 . Among cases, the biological specimen preceded the MI by

Poster Abstracts

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CROI 2016