Investigating the effect of antiretroviral switch to tenofovir alafenamide on lipid profiles in people living with HIV within the UCD ID Cohort

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1 Investigating the effect of antiretroviral switch to tenofovir alafenamide on lipid profiles in people living with HIV within the UCD ID Cohort A. Lacey 1, W. Tinago 1, E. Alvarez Barco 1, A.J. Macken 1, G. Sheehan 2, J.S. Lambert 2, A.G. Cotter 1,2, P.W.G. Mallon 1,2 1 HIV Molecular Research Group, University College Dublin School of Medicine, Dublin, Ireland 2 Mater Misericordiae University Hospital, Department of Infectious Diseases, Dublin, Ireland UCD School of Medicine Scoil an Leighis UCD Mater Misericordiae University Hospital

2 Background Tenofovir disoproxyl fumarate (TDF) has been a preferred firstline NRTI for the last decade 1, but has been associated with increased risk of bone loss 2 and renal dysfunction 3 TDF has been shown to have a lipid lowering effect; improving TC, LDL and HDL levels in People Living with HIV (PLWH) 4 Whilst reporting improved renal and bone safety profiles, studies have noted changes in lipid profiles in PLWH switching away from TDF to tenofovir alafenamide (TAF) 5,6 Changes in lipid profiles observed with TAF use in PLWH remain poorly characterised 1. ART Guidelines, WHO Bedimo R et al. AIDS 2012, 26: Mocroft A et al. AIDS 2010, 24: Tungsiripat et al. AIDS 2010, 24: Sax PE et al. Lancet 2015, 385(9987): Thompson M et al. IDWeek, 2015, Abstract 725

3 Objective To characterise changes in lipids observed after switching to TAF-containing ART in a real-world setting

4 Methods Study Design and Population Retrospective analysis on UCD ID Cohort subjects who switched to TAF-containing ART by May 2017 Study Assessments Data collected at baseline and followup Demographic information, ART history, use of lipid-lowering therapy (LLT) Routine clinical laboratory data HIV RNA, CD4+ T-cell count & lipid profiles (TC, LDL, HDL, TG) Lipid Stratification NCEP-ATPIII criteria were used to assess severity of dyslipidaemia 1. Adult Treatment Guidelines III. National Institute of Health, National Cholesterol Education Programme. 2016

5 Methods NCEP ATP III Guidelines The National Cholesterol Education Programme released their Adult Treatment Panel III in These guidelines outline thresholds for dyslipidaemia as follows: Total Cholesterol (mmol/l) LDL (mmol/l) HDL (mmol/l) Triglycerides (mmol/l) Normal Borderline Abnormal Dyslipidaemia Severe Dyslipidaemia < >7.2 Very Severe Dyslipidaemia < >4.9 > <1.03 < > Adult Treatment Guidelines III. National Institute of Health, National Cholesterol Education Programme. 2016

6 Methods NCEP ATP III Guidelines The National Cholesterol Education Programme released their Adult Treatment Panel III in Not Dyslipidaemia Dyslipidaemia Normal Borderline Abnormal Dyslipidaemia Severe Dyslipidaemia Very Severe Dyslipidaemia Total Cholesterol (mmol/l) LDL (mmol/l) HDL (mmol/l) Triglycerides (mmol/l) < >7.2 < >4.9 > <1.03 < > Adult Treatment Guidelines III. National Institute of Health, National Cholesterol Education Programme. 2016

7 Methods Study Design and Population Retrospective analysis on UCD ID Cohort subjects who switched to TAF-containing ART by May 2017 Study Assessments Data collected at baseline and followup Demographic information, ART history, use of lipid-lowering therapy (LLT) Routine clinical laboratory data Viral Load, CD4 count & lipid profiles Lipid Stratification NCEP-ATPIII criteria were used to assess severity of dyslipidaemia Statistical Analysis Between-group comparisons: Mann Whitney or chi square tests Within-group comparisons: Wilcoxon Signed-Rank, McNemar, or McNemar-Bowker tests 1. Adult Treatment Guidelines III. National Institute of Health, National Cholesterol Education Programme. 2016

8 Population breakdown Followup lipids taken from first available lipid profile at least 7 days post switch (median 154 [ ]) 774 PLWH enrolled to the UCD ID Cohort (May 2017) 191 switched to TAF (July 2016 May 2017) Pre- and post-lipid data available for 110

9 Baseline characteristics Variables, n(%) (unless specified) Total switch to TAF (191) Analysed (110) Age, median [IQR] 45 [37 51] 46 [39 53] Male 128 (67%) 81 (73.6%) Caucasian 130 (68.1%) 76 (69.1%) African 51 (26.7%) 30 (27.3%) Heterosexual acquisition 71 (37.2%) 42 (38.2%) MSM acquisition 63 (33.0%) 40 (36.4%) IVDU acquisition 46 (24.1%) 22 (20.0%) HIV/HCV co-infection 42 (22.5%) 19 (17.3%) Years since HIV diagnosis, median [IQR] 10 [5 15] 10 [ ] MSM: Men who have sex with men IVDU: Intravenous drug users HCV: Hepatitis C virus P

10 Baseline HIV-related variable Variables, n(%) (unless specified) Total switch to TAF (191) Analysed (110) CD4 (cells/μl), median [IQR] 577 [ ] [ ] Viral Load <40 copies/ml 167 (87.4%) 101 (91.8%) Use of lipid lowering therapy 40 (20.9%) 33 (30.3%) ART backbone pre-switch to TAF: TDF 166 (86.9%) 92 (83.6%) Abacavir 18 (9.4%) 11 (10.0%) Other* 7 (3.7%) 7 (6.4%) *(Dolutegravir, Raltegravir, Etravirine) P

11 ART regimens pre and post switch Variables, n(%) (unless specified) Total switch to TAF (191) Most common ART regimens pre-switch to TAF: Analysis (110) Atripla 42 (22.5%) 27 (24.5%) Stribild 37 (19.4%) 24 (21.8%) TDF/FTC/DOL 30 (15.7%) 14 (12.7%) Most common ART regimens post-switch to TAF: Genvoya 112 (58.6%) 71 (64.5%) TAF/FTC/DOL 33 (17.3%) 19 (17.3%) TAF/FTC/DAR/C 18 (9.4%) 7 (6.4%) (39.9%) analysed subjects had a directly comparable switch, with TAF being the only new component introduced to their ART regimen at switch P

12 Lipid Increases post switch (n=110) 6.00 p=0.001 Median lipid values (mmol/l) p=0.006 p=0.023 p=0.405 p= BL FU BL FU BL FU BL FU BL FU Total cholesterol LDL HDL Triglycerides TC:HDL P-values derived from Wilcoxon Signed-Rank test

13 Incidence of Dyslipidaemia (n=110) Dyslipidaemia defined as per NCEP ATP III guidelines 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% p=0.012 p=0.003 p=0.556 p= % 15.5% 26.4% 42.3% 30.9% 27.3% 20.0% 20.0% BL FU BL FU BL FU BL FU Total Cholesterol LDL HDL Triglycerides Normal/Borderline Abnormal Dyslipidaemic P-Values derived from McNemar test 1. Adult Treatment Guidelines III. National Institute of Health, National Cholesterol Education Programme. 2016

14 Stratified Lipid Profiles by NCEP ATPIII Guidelines p=0.003 p=0.080 p=0.259 p= % 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% BL FU BL FU BL FU BL FU Total Cholesterol LDL HDL Triglycerides Normal Borderline Abnormal Dyslipidemia Severe Dyslipidaemia Very Severe Dyslipidaemia P-Values derived from McNemar-Bowker test

15 Stratified Lipid Profiles by NCEP ATPIII Guidelines p=0.003 p=0.080 p=0.259 p= % 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 4.6% 11.8% BL FU BL FU BL FU BL FU Total Cholesterol LDL HDL Triglycerides Normal Borderline Abnormal Dyslipidemia Severe Dyslipidaemia Very Severe Dyslipidaemia P-Values derived from McNemar-Bowker test

16 Summary These data suggest worsening lipid profiles post switch to TAF A larger proportion of PLWH exceeded recommended lipid thresholds post-switch despite no differences in TC:HDL ratio Further studies are needed to ascertain whether this worsening of lipid profiles with TAF-switch might be driven by TAF initiation or by TDF cessation How these changes will impact on cardiovascular risk or need for LLT remains to be determined

17 Limitations Small dataset Large proportion of population were receiving TDF at baseline, limiting our ability to differentiate between TDFcessation related effects and TAF-initiation related effects on lipid profiles Analysed population had a higher incidence of use of LLT, and an additional three subjects in the analysis population commenced LLT post TAF-switch and prior to measurement of followup lipids

18 Acknowledgements Mater Misericordiae University Hospital, Infectious Diseases Clinic Patients and Staff