CROI 2019 Abstract eBook

Abstract eBook

Poster Abstracts

that ABC impacts platelet activation independently of the issues that confound studies in patients; providing potential mechanisms for ABC-associated CV risk in patients (Fig. 1).

recommend direct oral anticoagulants (DOACs) over warfarin for VTE treatment in patients without cancer due to less bleeding as well as less frequent monitoring resulting in greater patient and provider convenience. However significant drug interactions exist among DOACs and ART. Use of p-glycoprotein/ CYP3A4 inhibitors such as ritonavir (RTV) or cobicistat (COBI) with rivaroxaban (RVB) is not recommended; with apixaban (APB) and dabigatran (DBG), DOAC dose reduction is needed. We characterized evolving trends in oral anticoagulant use and the prevalence of concomitant use of DOACs with RTV or COBI boosted ART among PLWH. Methods: Established in 2011, the DC Cohort is a clinic-based, longitudinal observational cohort of PLWH. Participants from 11 sites who were prescribed anticoagulants from 1/2011-3/2017 were included. Duration of anticoagulant use was calculated. Summary statistics were generated for demographic and clinical characteristics, including concomitant ART prescriptions. Descriptive statistics of individuals prescribed DOACs and warfarin were generated. Results: Among 8,315 PLWH enrolled during the study period, there were 239 anticoagulant prescriptions (96 DOAC, 143 warfarin) for 207 persons. PLWH prescribed anticoagulants were mostly Black (82%), male (82%), with a median age of 56 yrs. At the time of anticoagulant prescription, 95%were prescribed ART; 76% had CD4 counts >200 cells/uL and 77% had HIV RNA <200 c/ml. In 2011, DOACs accounted for 3% of total anticoagulant use, which increased to 43% in 2016. DOACs accounted for 64% of all new anticoagulant prescriptions by 2016 [Figure 1]. RVB was the most frequently prescribed DOAC (70%) in 2016, followed by APB (19%), and DBG (11%). Among PLWH on DOACs, 59%were on boosted ART prior to DOAC; 1 month after DOAC initiation, this decreased to 33%. 55% in the RVB group were receiving boosted ART prior to anticoagulant initiation. Despite the recommendation to avoid concomitant use, 29% still received boosted ART 1 month after RVB initiation. Dose adjustments for APB and DBG when given with interacting ART could not be assessed. Conclusion: In this cohort, DOAC use increased significantly over time. Although RVB is not recommended with RTV or COBI, concomitant use was frequently seen. Feedback should be provided to clinicians on DOAC utilization trends and potential ART drug interactions.

640 PLATELET FUNCTION AFTER DOLUTEGRAVIR AND/OR DARUNAVIR/ COBICISTAT IN HEALTHY SUBJECTS Kirk A. Taylor 1 , Francesca Ferretti 2 , Maddalena Cerrone 2 , Akif A. Khawaja 1 , Wing Yip 1 , Marta Boffito 2 , Michael Emerson 1 1 Imperial College London, London, UK, 2 Chelsea and Westminster NHS Foundation Trust, London, UK Background: The effects of antiretroviral combinations upon platelets and cardiovascular health remain unclear. Although data have been presented on the effect of certain nucleoside reverse transcriptase inhibitors (NRTIs), third agents have not been studied in this context in isolation. Both dolutegravir (DTG) and darunavir/cobicistat (DRV/c) are effective third agents recommended by International HIV treatment guidelines. Methods: Platelets were isolated from two populations of HIV-negative volunteers: 1) Subjects that were not taking any medication whose platelets were pre-incubated with ARVs in vitro and 2) 21 subjects enrolled on a Phase I clinical trial (NCT03094507) who were randomised to two groups. Group one received DTG (50mg, QD), DTG plus Cobi-boosted darunavir (DRV/c; 800/150mg QD) and DRV/c for 7 d with a 14 d washout period between drugs. Group two followed the same sequence but started with DRV/c and ended on DTG. Platelets were isolated pre-dose and after achieving steady-state for each drug intervention. Intra-subject analysis was performed to compare platelet function at each time point. For in vitro studies, platelets were exposed to each drug at Cmax values derived from the clinical trial. Plate-based aggregometry and flow cytometry was used to assess platelet function. Results: Platelet aggregation responses were reduced for subjects taking daily DTG (13.9±4.7% for 3µM ADP and 13.8±4.7% for 10µM TRAP6). This effect was lost when subjects were taking DTG/DRV/c and there was no effect of DRV on maximum platelet aggregation. Maximum aggregation values for platelets isolated from ARV-naïve volunteers were not affected by clinically-relevant concentrations of DTG or DRV. However, DTG reduced collagen-evoked alpha and dense granule release 80.6±10.1% and 71.5±13.1%, respectively. Whereas DRV increased alpha and dense granule release 2.2±0.4- and 1.2±0.2-fold, respectively. Conclusion: The mechanism for reduced platelet activation in the presence of DTG may be explained by altered platelet granule release, that confers a potentially cardioprotective phenotype. Enhanced granule release following acute exposure to DRV may be important in the context of protease inhibitor- related cardiovascular risk. Further studies are required to correlate our basic science and clinical approaches to understand the potential impacts of alternative novel therapies upon cardiovascular health in people living with HIV. 641 DIRECT ORAL ANTICOAGULANT AND ART USAGE IN PLWH: DATA FROM THE DC COHORT Safia S. Kuriakose 1 , Jomy M. George 2 , Anne K. Monroe 3 , Qingjiang Hou 4 , Alice K. Pau 5 , Henry Masur 2 , Colleen Hadigan 5 , Amanda D. Castel 3 , Michael A. Horberg 6 , for the DC Cohort Executive Committee 1 Leidos Biomedical Research, Inc, Frederick, MD, USA, 2 NIH, Bethesda, MD, USA, 3 George Washington University, Washington, DC, USA, 4 Cerner Corp, Kansas City, MO, USA, 5 NIAID, Bethesda, MD, USA, 6 Kaiser Permanente Mid-Atlantic States, Rockville, MD, USA Background: People living with HIV (PLWH) may develop age-related comorbidities including venous thromboembolism (VTE). The CHEST guidelines

Poster Abstracts

642 VIRAL PERSISTENCE IS INDEPENDENTLY PREDICTIVE OF ATHEROSCLEROSIS IN TREATED HIV

Megan McLaughlin 1 , Yifei Ma 1 , Rebecca Scherzer 2 , Smruti Rahalkar 1 , Teri Liegler 1 , Jeffrey N. Martin 1 , Claire Mills 1 , Steven G. Deeks 1 , Priscilla Hsue 1 1 University of California San Francisco, San Francisco, CA, USA, 2 San Francisco VA Medical Center, San Francisco, CA, USA Background: Persons with HIV have an increased risk for cardiovascular disease, and inflammation is thought to underlie this excess risk. The impact of viral persistence and the reservoir on atherosclerosis has not been described. We hypothesized that higher levels of viral persistence would be associated with atherosclerosis as assessed by carotid artery intima-media thickness (IMT) progression over time and that viral persistence levels would be associated with markers of chronic inflammation and higher mortality. Methods: IMT, a validated marker of atherosclerosis, was assessed over time in a cohort of treated HIV-infected adults enrolled in the SCOPE cohort. Levels of cell-associated HIV RNA (assessment of reservoir size) and DNA (ongoing level of viral replication) were isolated from cryopreserved peripheral blood

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