CROI 2020 Abstract eBook

Abstract eBook

Poster Abstracts

groups. In unadjusted analysis, OC and CTX-1 negatively correlated with BMD-LS and BMD-FN, and RBP/Cr with BMD-FN. In adjusted analyses, compared to the noTDF/noPI group, those on TDF/PI were 4 times more likely to have low BMD-FN and those on TDF and/or PI 3 times more likely to have low BMD-LS (Table, model 1).Further adjustment for the OC, CTX-1 and RBP/Cr had minimal impact on the observed associations (models 2-3) Conclusion: Exposure to ART rather than levels of bone turnover or renal tubular markers best predicts low BMD in older PWH. Treatment with TDF/PI combined predicted low BMD-FN while TDF with or without PI predicted low BMD-LS. These data do not support routine measurement of biomarkers to predict low BMD in older PWH

695 BONE DENSITY IN ART TREATED HIV+ AND HIV– SUBJECTS IN FOLLOW UP; HIV UPBEAT RESULTS Tara McGinty 1 , Willard Tinago 1 , Alan Landay 2 , Aoife G. Cotter 1 , Caroline Sabin 3 , Alan Macken 1 , Eoin Kavanagh 4 , Gerard Sheehan 4 , John Lambert 1 , Patrick W. Mallon 1 , for the HIV UPBEAT Study Group 1 University College Dublin, Dublin, Ireland, 2 Rush University Medical Center, Chicago, IL, USA, 3 University College London, London, UK, 4 Mater Misericordiae University Hospital, Dublin, Ireland Background: Decreases in bone mineral density (BMD) in people with HIV (PWH) have been associated with intiation of antiretroviral therapy (ART) containing tenofovir disproxil fumarate (TDF). With recent introduction of new ART strategies we aimed to explore the effect of switching to non-TDF regimes on BMD. Methods: HIV UPBEAT, a single site, prospective cohort study recruited PWH and a comparable HIV- group from 2011 to 2017. Demographic, clinical, medication history and BMD measured by DXA at lumbar spine (LS) and femoral neck (FN) were recorded at 4 visits over at least 5years. Subjects with at least 2 DXA were included in the analysis. We used linear mixed models to determine predictors of rate of absolute change in BMD adjusting for HIV status, age, gender, ethnicity, BMI and smoking status for the whole cohort and discontinuous change mixed models to assess effect of switching-off TDF in the PWH subgroup, excluding those who switched back to TDF. Data are median[IQR] unless specified Results: Of 409 subjects, 191(47%) were PWH (62%male, 61% Caucasian, age 40 [34-47] yrs) and 218 were HIV- (45%male, 77% Caucasian, age 42[35-50] yrs). The PWH group were 32%MSM, 18% IVDU and 50% heterosexual, with 11[8,14] yrs since HIV diagnosis and 7.9 [6,10.3] yrs cumulative ART. 76%were on TDF at visit 1 with 48 (28%) subjects switching off TDF over 7.3 [3.7, 9.5] yrs follow-up. Neither absolute or percentage (%) change in BMD, nor the rate of change of LS or FN BMD differed between PWH and HIV- subjects (absolute % change in BMD; LS 0.15 [-3.48, 3.52] vs -0.62[-3.99, 3.09],P=0.49 and FN 0.63 [-3.69, 4.69] vs -0.55 [-4.26, 3.97],P=0.31, respectively). PWH had a net ( although not statistically significant) gain in LS and FN BMD evident in later visits (Fig 1), resulting in no significant difference in LS or FN BMD between groups at visit 4. In PWH, switching off TDF was independently associated with increases in LS BMD +0.004 g/cm 2 /yr[0.001, 0.007], P=0.005 but not FN BMD, while those switched to TDF had significant decline in mean FN and LS BMD (Fig 1) Conclusion: In a contemporary cohort of ART treated PWH change in BMD was similar over time regardless of HIV status, with no between-group difference in BMD at last study follow up. Switching away from TDF was independently associated with increases in LS BMD suggesting reversal of prior reduction in BMD in PWH to levels comparable to the HIV- population

694 BONE MINERAL DENSITY IMPROVES IN WOMEN WHO SWITCH FROM TDF/FTC/NNRTI TO ABC/3TC/DTG Fowzia Ibrahim 1 , Amanda Samarawickrama 2 , Yvonne Gilleece 3 , Julie Fox 4 , Nargis Hemat 5 , Stephen Kegg 6 , Chloe Orkin 7 , Lisa Hamzah 8 , Jonathan Ainsworth 9 , Birgit Barbini 10 , Lucy Campbell 1 , Frank Post 10 , for the BESTT Trial Team 1 Kings College London, London, UK, 2 Chelsea and Westminster NHS Foundation Trust, London, UK, 3 Brighton & Sussex University Hospitals NHS Trust, Brighton, UK, 4 Guy’s and St Thomas’ NHS Foundation Trust, London, UK, 5 Royal Free Hospital, London, UK, 6 Lewisham and Greenwich NHS Trust, London, UK, 7 Barts Health NHS Trust, London, UK, 8 King's College Hospital, London, UK, 9 North Middlesex University Hospital, London, UK, 10 King's College Hospital NHS Foundation Trust, London, UK Background: Tenofovir disoproxil fumarate (TDF) is associated with decreased bone mineral density (BMD) which is of particular concern to peri/post- menopausal women. We hypothesized that BMD and renal tubular function would improve in women who switch from a TDF- and NNRTI-containing regimen to abacavir/lamivudine/dolutegravir (ABC/3TC/DTG). Methods: We conducted a randomized controlled trial (Bone Evaluation in women who Switch from TDF/FTC/NNRTI to Triumeq [BESTT, EudraCT 2015- 005297-37]) in which HLA-B5701 negative women aged ≥40 years with HIV RNA <50 copies/mL on TDF/FTC/NNRTI for ≥12 months were randomized 1:2 to continue TDF/FTC/NNRTI or switch to ABC/3TC/DTG for 96 weeks. Primary endpoint was change from baseline in total hip BMD at week 48. Secondary endpoints included changes in lumbar spine BMD, bone turnover, renal tubular function and (post-hoc) weight. Linear regression was used to estimate the mean difference from baseline to week 48 between the two study arms, using multiple imputation with chained equations for missing BMD data. Results: Ninety-one women (86% black ethnicity, mean [SD] age 50.4 [6.6] years, CD4 cell count 639 [263] cells/mm 3 , BMI 30.3 [6.5] kg/m 2 ) were randomized; 29/32 (91%) in the TDF/FTC/NNRTI vs. 51/59 (86%) in the ABC/3TC/ DTG arm continued through week 48. Women who switched to ABC/3TC/DTG maintained viral suppression and experienced improvements in total hip and lumbar spine BMD and proteinuria (Table). No change in vitamin D, parathyroid hormone, bone turnover markers (CTx and P1NP), estimated glomerular filtration rate (eGFR-cystatin C) or fractional excretion of phosphate was observed. Switching to ABC/3TC/DTG was associated with an improved CD4 cell count (adjusted mean difference 74.0 [6.9, 141.2] cells/mm 3 , p=0.032) and 1.8kg weight gain vs. no change in those who continued TDF/FTC/NNRTI (adjusted mean difference 1.81 [0.03, 3.59] kg, p=0.046); weight increased >5% from baseline in 37% vs. 0% (p<0.001). Nine participants (15%) discontinued ABC/3TC/DTG for drug-associated adverse events (hypersensitivity, N=2; neuropsychiatric, N=5; other, N=2). Conclusion: Switching from TDF/FTC/NNRTI to ABC/3TC/DTG resulted in improvements in BMD, proteinuria and CD4 cell count. However, the possible benefits of these need to be balanced against weight gain and treatment- limiting adverse events.

Poster Abstracts

CROI 2020 254