CROI 2018 Abstract eBook

Abstract eBook

Poster Abstracts

Background: Tenofovir disoproxil fumarate (TDF) containing combination antiretroviral therapy (cART) can result in unfavorable metabolic changes. These may recover after TDF discontinuation. We measured renal, bone, lipid and inflammatory markers before and after a switch from TDF-containing cART to dolutegravir (DTG) monotherapy in the DOlutegravir maintenance MONOtherapy for HIV (DOMONO) study (NCT02401828). Methods: In DOMONO patients were switched from cART to DTG maintenance monotherapy. Eligible patients had been on cART with HIV-RNA < 50 c/ml for >6 months and with a CD4-nadir and HIV-RNA-zenith ≥200 cells/mm 3 and >100.000 c/ml respectively. The study was discontinued prematurely due to an unforeseen number of virological failures with acquired resistance in integrase in 3 patients (CROI 2017, abstract 451LB). In the entire subgroup of patients on a TDF-containing cART (‘TDF’) before DTG monotherapy initiation, the following makers were measured at week 0, 24 and 48; (1) Bone Mineral Density (BMD) and Trabecular Bone Score (TBS), (2) estimated glomerular filtration rate (eGFR), urine protein:creatinine-ratio (UPCR), urine albumin:creatinine-ratio (UACR) and urine beta-2 microglobulin:creatinine-ratio (UB2MGCR), (3) lipids and (4) C-reactive protein and CD4:8 T-cell-ratio as markers of inflammation and immune activation. Paired T-tests and Wilcoxon Rank Sum tests were used to compare week 0 with week 48 and standard deviations and interquartile ranges are given when appropriate. Results: 85 patients on TDF were included and were mostly male with a mean age of 47 years. Mean baseline eGFR was 90 ml/min and mean (SD) lumbar and hip BMD at baseline were 1.174 (0.161) and 1.009 (0.156) g/cm3 and TBS of 1.313 (0.119). Lumbar and total hip BMD improved at week 48: +1.8% and +1.5% respectively (p<0.01 for all). Mean TBS improved as well by week 48: +0.012, p<0.01. As expected, the start of DTG led to a decrease in the creatinine-based eGFR measurement of -6.7 (9.2) ml/min at week 48. However, other renal markers improved significantly (p<0.01 for all) (figure 1). Lipids did not change significantly (LDL +0.14, TC/HDL +0.1 p>0.1 for all), and neither did CRP (+0.00, p>0.1) and CD4:8-ratio (+0.00, p>0.1). Conclusion: In those patients without virological failure at week 48, a switch from TDF-containing cART to DTG monotherapy improved bone and renal markers and had a neutral effect on lipids and inflammatory and immune activation parameters. Juan M. Tiraboschi , Antonio Navarro-Alcaraz, Elena Ferrer, Carmen Gomez- Vaquero, Dolors Giralt, Arkaitz Imaz, Maria Saumoy, Daniel Podzamczer Bellvitge University Hospital, Barcelona, Spain Background: Osteopenia and osteoporosis are common comorbidities in HIV- infected patients and low level residual systemic inflammation is thought to be a contributor to these disorders. Omega-3 fatty acids (O3FAs) have beneficial effects on triglycerides and systemic inflammation. The anti-inflammatory effects of O3FAs are well-known and they are mediated through multiple mechanisms. We performed a randomized clinical trial in HIV-infected patients with hypertriglyceridemia, to compare the effects of O3FAs vs Fenofibrate in bone mineral density (BMD) and markers of bone turnover. Methods: HIV-infected subjects on stable ART were randomized to receive either Omega-3-acid (O3) 2000mg/day or micronized fenofibrate 145 mg/day for 24 months. The primary outcomes were changes on BMD measured by hip and lumbar bone densitometry (DEXA Hologic QDR 4500)), The secondary outcomes were changes bone turnover markers such as PTH, calcitonin, CTX, BGLAP and 1,25-(OH)2D3 and serum triglycerides (TG). All markers were compared between the groups at pre-specified time points during the trial, as were changes in these parameters from baseline. Results: Fifty eight virologically suppressed patients (13% female) were allocated to fenofibrate (n=30) or O3 (n=28), 12 pts (40%) in the fenofibrate group were over 50 years old and 15 (53%) in the O3 group (p:0.3). Mean CD4 count was 739 cells/ml (SD 251) and 650 cells/ml (SD 263) respectively. 63 % of pts in the fenofibrate group and 42% in the O3 group received ARV regimens

724 COMBINED EFFECTS OF BISPHOSPHONATES & TDF → TAF SWITCH IN HIV+ ADULTS WITH LOW BMD Todd T. Brown 1 , Michael T. Yin 2 , Samir K. Gupta 3 , William R. Short 4 , Melanie Thompson 5 , Daniel Podzamczer 6 , Giovanni Di Perri 7 , Cheryl McDonald 8 , Matthias Cavassini 9 , Pablo Tebas 4 , Ya-Pei Liu 10 , Scott McCallister 10 , Andrew Cheng 10 , Moupali Das 10 1 Johns Hopkins University, Baltimore, MD, USA, 2 Columbia University Medical Center, New York, NY, USA, 3 Indiana University, Indianapolis, IN, USA, 4 University of Pennsylvania, Philadelphia, PA, USA, 5 AIDS Research Consortium of Atlanta, Atlanta, GA, USA, 6 Hospital Universitario de Bellvitge, Barcelona, Spain, 7 Amedeo di Savoia Hospital, Torino, Italy, 8 Tarrant County Infectious Disease Associates, Fort Worth, TX, USA, 9 Lausanne University Hospital, Lausanne, Switzerland, 10 Gilead Sciences, Inc, Foster City, CA, USA Background: Bone mineral density (BMD) improves by 2-3% in HIV+ adults who switch from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF). The extent to which these increases can be augmented with concomitant bisphosphonate (BP) use is unknown. Methods: We pooled data from two prospective 144-week, Phase 3 studies of HIV-infected adults virologically suppressed on TDF-based regimens who switched to elvitegravir, cobicistat, and emtricitabine (E/C/F) co-formulated with TAF. In adults with clinically significant low BMD by dual energy x-ray absorptiometry (T-score ≤-2.0 at lumbar spine, femoral neck, or total hip) at baseline (BL), we compared the percentage change in BMD and change in T-score at the lumbar spine and total hip in BP users v. non-users over 144 weeks. We estimated the effect of BP use on bone outcomes independent of age, race, sex, BMI, current smoking status, and BL BMD with linear regression. Results: Of 1117 adults enrolled who switched from TDF to TAF, 214 (19%) had clinically significant low BL BMD, of whom 43% (93/214) had osteoporosis. Over 144 weeks, 30/214 (14%) reported using BPs with median (Q1, Q3) use of 754 (425, 1032) days. At BL, BP users were more likely to be women (33% vs 12%), to be current smokers (40% vs 23%), and to have lower spine and hip BMD. At 144 weeks, spine BMD increased by the mean (Q1, Q3) of 5.1% (4.0, 8.3) (p<0.001) in the BP users and 2.6% (-0.5, 5.4) (p<0.001) in the non-BP users (between group p=0.002). In the hip, median (Q1, Q3) BMD increased in BP users [4.0% (1.2, 6.7)] (p<0.001) and non-users [2.3% (0.9, 4.4)] (p<0.001) with no difference between the groups (p=0.29). In multivariable models, compared to non-users, BP users tended to have greater increase in lumbar spine BMD [2.6% (95% CI: -0.3, 5.4); p=0.08], corresponding to a 0.21 (95% CI:-0.01, 0.42; p=0.06) T-score increase. At the hip, the magnitude of the increase in BMD and T-score was similar in BP vs non-users (p>0.80). Conclusion: Switching from TDF to TAF improved BMD over 144 weeks in HIV+ adults with low BMD. In this cohort, concomitant BP use augmented these gains at the spine but not the hip. Future controlled studies are required to confirm these findings and examine whether a sequential strategy of TDF switching followed by BP use would result in improved BMD gains compared to a combined strategy of concomitant TDF switching plus BP use. 725 BONE, RENAL, AND INFLAMMATION MARKERS IN THE DOLUTEGRAVIR MONOTHERAPY (DOMONO) STUDY Ingeborg Wijting 1 , Casper Rokx 1 , Sandra A. Smits 1 , M. C. Zillikens 1 , Theodora de Vries-Sluijs 1 , Karin Schurink 1 , Hannelore Bax 1 , Maarten Derksen 1 , Elrozy Andrinopoulou 1 , Ineke van der Ende 1 , Eric van Gorp 1 , Jan Nouwen 1 , Annelies Verbon 1 , Wouter Bierman 2 , Bart Rijnders 1 1 Erasmus University Medical Center, Rotterdam, Netherlands, 2 University Medical Center Groningen, Groningen, Netherlands

Poster Abstracts

726 OMEGA-3 FATTY ACID SUPPLEMENTATION IN HIV PATIENTS: A RANDOMIZED CLINICAL TRIAL

CROI 2018 270