CROI 2018 Report Back

Transcription

1 CROI 2018 Report Back Monika Roy, MD MAS Assistant Professor Division of HIV, Infectious Diseases, and Global Medicine bayareaaetc.org 1

2 Disclosures and Conflicts of Interest Nothing to report bayareaaetc.org 2

3 Overview ART Treatment Trials Drug resistance Opportunistic infections Co-morbidities bayareaaetc.org 3

4 A. ANTIRETROVIRAL TREATMENT TRIALS bayareaaetc.org 4

5 Bictegravir Trials Trial Name Type/ Resistance or prior failure allowed? Comparators Result GS1489 Start in naïve/ NONE BIC/TAF/FTC vs DTG/ABC/3TC Non-inferior (Gallant Lancet HIV 2017). Less nausea GS1490 Start in naïve/ NONE BIC/TAF/FTC vs DTG/TAF/FTC Non-inferior (Sax. Lancet HIV 2017) GS1878 Switch from boosted PI/ no failure or resistance even to 3TC Switch from boosted PI/2 NRTIs to BIC/TAF/FTC Non-inferior (ID week Oct 2017). Better lipids GS 1844 Switch from DTG/ABC/3TC/ no resistance BIC/TAF/FTC vs DTG/ABC/3TC Non-inferior (CROI 2018) bayareaaetc.org Slide courtesy M. Gandhi

6 Study : Switch From Suppressive DTG/ABC/3TC to BIC/FTC/TAF Randomized, double-blind, international, active-controlled phase III trial Primary endpoint: Wk 48 HIV-1 RNA 50 c/ml (FDA snapshot; noninferior. margin: 4%) Wk 48 Pts with HIV-1 RNA < 50 c/ml for 3 mos on DTG/ABC/3TC*; egfr CG 50 ml/min; no active HBV; no known resistance to study drugs (N = 563) BIC/FTC/TAF (n = 282) DTG/ABC/3TC (n = 281) Open-label extension with BIC/FTC/TAF Baseline: male sex, 88% to 90%; black race, 21% to 22%; median age, yrs; median CD4+ cell count, cells/mm 3 ; median egfr CG, 101 ml/min *Could be STR or as separate components. All pts also received placebo tablets for comparator regimen. BIC/FTC/TAF 50/200/25 mg PO QD. DTG/ABC/3TC 50/600/300 mg PO QD. Molina J-M, et al. CROI Abstract O22. Slide credit: clinicaloptions.com

7 Switch From Suppressive DTG/ABC/3TC to BIC/FTC/TAF: Virologic Outcomes at Wk 48 Outcome at Wk 48, n (%) Switch to BIC/FTC/TAF (n = 282) Continued DTG/ABC/3TC (n = 281) Treatment Difference, % (95.002% CI) No treatment-emergent resistance detected in any pt P Value HIV-1 RNA 50 copies/ml 3 (1.1) 1 (0.4) 0.7 (-1.0 to 2.8).62 HIV-1 RNA < 50 copies/ml 264 (93.6) 267 (95) NR.59 No virologic data 15 (5.3) 13 (4.6) NR NR Molina J-M, et al. CROI Abstract O22. Slide credit: clinicaloptions.com

8 Switch From Suppressive DTG/ABC/3TC to BIC/FTC/TAF: Safety Outcomes at Wk 48 Outcome, n (%) *Fischer exact test P =.01. BIC/FTC/TAF (n = 282) DTG/ABC/3TC (n = 281) Any TRAE 23 (8)* 44 (16)* TRAE in 1% of pts Headache Abnormal dreams Flatulence Nausea Diarrhea Fatigue Insomnia 7 (3) 1 (< 1) (< 1) 1 (< 1) 0 8 (3) 5 (2) 5 (2) 5 (2) 4 (1) 3 (1) 3 (1) Any gr 3/4 lab abnormality 47 (17) 32 (11) Gr 3/4 lab abnormalities in 2% of pts LDL elevation Increased amylase ALT elevation CK elevation Fasting hyperglycemia 14 (5) 7 (2) 6 (2) 6 (2) 6 (2) 13 (5) (2) 2 (< 1) Median egfr CG change from BL: BIC arm, 1.0 ml/min; DTG arm, -1.8 ml/min; P <.001 No significance differences between arms in changes from BL for proteinuria levels, spine and hip BMD No significant differences in changes for fasting lipids, except triglycerides Median change for triglycerides: BIC arm, -5 mg/dl; DTG arm, +3 mg/dl; P =.028 Molina J-M, et al. CROI Abstract O22. Slide credit: clinicaloptions.com

9 Switch From Suppressive PI- or INSTI-Based ART to BIC/FTC/TAF in Women Open-label, randomized, active-controlled phase III trial Primary endpoint: Wk 48 HIV-1 RNA 50 c/ml (FDA snapshot; noninferior. margin 4%) Pts from Uganda (27%), Russia (24%), Thailand (22%), US (15%), Dominican Republic (12%) Wk 48 Pts with HIV-1 RNA < 50 c/ml for 6 mos on EVG/COBI/FTC/(TAF or TDF) or ATV + RTV + FTC/TDF; CrCl 50 ml/min (N = 470) BIC/FTC/TAF* (n = 234) Continued Baseline Regimen (n = 236) Median baseline values: age, yrs; CD4+ cell count, cells/mm 3 Regimen at randomization: EVG/COBI/FTC/TAF, 53%; EVG/COBI/FTC/TDF, 42%; ATV + RTV + FTC/TDF, 5% *BIC/FTC/TAF 50/200/25 mg PO QD. Kityo C, et al. CROI Abstract 500. Slide credit: clinicaloptions.com

10 ANDES: DRV/RTV + 3TC vs DRV/RTV + 3TC/TDF in Treatment-Naive Pts at Wk 48 Open-label, randomized phase IV study Primary endpoint: HIV-1 RNA < 50 c/ml at Wk 48 (FDA snapshot) Stratified by HIV-1 RNA ( or > 100,000 copies/ml) 24 Wks: Interim Analysis 48 Wks: Primary Endpoint ART-naive pts with HIV-1 RNA > 1000 copies/ml, no NRTI or PI resistance, and HBsAg negative (N = 145) DRV/RTV + 3TC* (n = 75) DRV/RTV + 3TC/TDF (n = 70) *DRV/RTV 800/100 mg QD + 3TC 300 mg QD. DRV/RTV 800/100 mg QD + 3TC/TDF 300/300 mg QD. Figueroa MI, et al. CROI Abstract 489. Slide credit: clinicaloptions.com

11 Pts (%) ANDES: Efficacy and Safety At Wk HIV-1 RNA < 50 copies/ml at Wk 48 (ITT) DRV/RTV + 3TC DRV/RTV + 3TC/TDF All Pts n/n = 70/75 66/70 Pts With BL HIV-1 RNA > 100,000 c/ml (n = 35) Treatment difference (HIV-1 RNA < 50 c/ml; ITT snapshot): All pts: -1.0% (95% CI: -7.5% to 5.6%) Pts with high BL HIV-1 RNA: -1.4 (95% CI: to 14.4) No significant difference in AEs leading to d/c, serious AEs, or deaths between arms TC change from BL significantly greater with dual ART vs triple ART (19% vs 4%; P =.01); LDL-C and TG trended toward greater increases with dual ART Figueroa MI, et al. CROI Abstract 489. Reproduced with permission. Slide credit: clinicaloptions.com

12 EMERALD: Subgroup Analysis of Switch to DRV/COBI/FTC/TAF In Suppressed Pts Subgroup analysis of randomized phase III noninferiority study assessing efficacy, safety according to number of prior VF, ARVs used [1] Wk 48 Pts with HIV-1 RNA < 50 c/ml while receiving boosted PI + FTC/TDF; no previous VF on DRV; egfr 50 ml/min* (N = 1141) Switch to DRV/COBI/FTC/TAF (n = 763) Continue Boosted PI + FTC/TDF (n = 378) DRV/COBI/FTC/TAF extension phase At Wk 48 primary analysis, switch to DRV/COBI/FTC/TAF noninferior to continued boosted regimen in terms of virologic rebound (primary endpoint); improved bone and renal markers with switch [2] Baseline: median age, yrs; median CD4+ cell count, cells/mm 3 Prior VF: 15%; prior ARVs: 4, 42%; 5-7, 31%; > 7, 27% *Eligible boosted PIs: ATV/COBI or RTV, DRV/COBI or RTV, LPV/RTV. Multiple previous ARVs permitted. Multiple VFs permitted on non DRV-based regimens. 800/150/200/10 mg QD. 1. Eron JJ, et al. CROI Abstract Orkin C, et al. Lancet HIV. 2018;5:e23-e34. Slide credit: clinicaloptions.com

13 Pts With Virologic Rebound (%) EMERALD: Virologic Rebound Through Wk 48 by Previous ART Experience Low virologic rebound rate across arms at Wk 48 regardless of number of previous VF or ARVs used Cumulative Virologic Rebound Through Wk 48 Switch to DRV/COBI/FTC/TAF Continued boosted PI + FTC/TDF (-1.5, 2.2) (-2.6, 2.0) (-4.8, 7.5) (-3.4, 3.1) 5 (-7.8, 5.9) n/n = 0/53 0 Overall Population 0 1 Prior VF 3.9 (-11.0, 13.7) Number of Prior ARVs Used -3.3 (-17.5, 2.7) 0.4 (-5.0, 3./9) /763 8/378 16/647 8/325 3/116 7/316 3/160 2/98 1/56 5/69 1/30 0/69 1/30 5/211 2/101 7 > 7 Eron JJ, et al. CROI Abstract 502. Reproduced with permission. Slide credit: clinicaloptions.com

14 DRIVE-AHEAD: Subgroup Analysis of Efficacy of First-line DOR/3TC/TDF vs EFV/FTC/TDF Subgroup analysis of double-blind, randomized phase III trial of DOR/3TC/TDF vs EFV/FTC/TDF in ART-naive pts (N = 734) [1] Efficacy of DOR/3TC/TDF noninferior to EFV/FTC/TDF in Wk 48 primary analysis [2] 1. Orkin C, et al. CROI Abstract Squires KE, et al. IAS Abstract TUAB0104LB. Slide credit: clinicaloptions.com

15 Doravirine Treatment Naïve Trials DRIVE-AHEAD (compared to EFV-based regimen) DRIVE-FORWARD (compared to DRV/r-based regimen) DRIVE-BEYOND (baseline resistance, ongoing) Switch Trials DRIVE-SHIFT (ongoing) Roles/Considerations on the use of Doravarine Superior lipid profile with DOR compared to EFV and DRV- based regimens Less neuropsychiatric side effects with DOR compared to EFV/FTC/TDF Two non-inferiority trials have been EFV and b/pi-based regimens, not INSTI NNRTIs not first line Co-formulated with TDF (not TAF) bayareaaetc.org 15

16 DTG PK Analysis From DolPHIN-1: DTG vs EFV As Initial ART In Late Pregnancy Interim DTG PK analysis from a multicenter, open-label, randomized trial evaluating pharmacokinetics of and virologic suppression with DTG or EFV + 2 NRTIs* in women with HIV presenting for initial ART during the third trimester of pregnancy (planned N = 60) Primary endpoint: DTG AUC wks after initiation and 2 wks postpartum DTG PK Parameter, Geometric Mean (95% CI) 3rd Trimester (n = 7) 2 Wks Postpartum (n = 2) Control AUC 0-24, ng h/ml 39,415 (28,296-50,534) Pt 1: Pt 2: 44,305 53,600 C max, ng/ml 2645 ( ) Pt 1: 4224 Pt 2: C 24, ng/ml 778 ( ) Pt 1: 1211 Pt 2: *Dosing: DTG 50 mg QD; EFV 600 mg QD. Reference data from nonpregnant HIV-infected pts receiving DTG in SPRING-1 and -2 studies. Waitt C, et al. CROI Abstract 807. Reproduced with permission. Slide credit: clinicaloptions.com

17 Take Home Messages New directions in ART Bictegravir: now FDA approved, single-pill combination (BIC/FTC/TAF (Bictarvy ), non-inferior to DTG/ABC/3TC in naïve & switch [GS 1844] DRV/RTV/3TC: more data for dual-therapy with PI/3T for trtmt naive, may benefit patients with renal failure [ANDES] DRV/Cobi/FTC/TAF (Symtuza ): single-pill, low virologic rebound in highly treatment experienced patient, may benefit patients with poor adherence [EMERALD] DOR/3TC/TDF: single-pill, non-inferior to EFV/FTC/TDF in treatment naive, potential role in patients who cannot tolerate integrase inhibitors bayareaaetc.org 17

18 Take Home Messages When should we use Bictarvy? Probably no benefit on side effects, lipids, bone, renal, drugdrug interactions, single pill compared to DTG/ABC/3TC BIC/TAF/FTC pricing similar to Triumeq Smaller pill Other considerations: HLAB57, CVD, Hepatitis B When should we not use Bictarvy? Don t use BIC/TAF/FTC with TB drugs No data in patients with previous failure or resistance No data in pregnancy bayareaaetc.org 18

19 B. DRUG RESISTANCE bayareaaetc.org 19

20 Impact of M184V on Virologic Efficacy of Switch to 3TC-Based Dual ART Retrospective observational study comparing efficacy of 3TC-based dual ART for pts with or without M184V history in Antiretroviral Resistance Cohort Analysis database (N = 436) Inclusion criteria: HIV RNA 50 copies/ml, switching to dual therapy (3TC + either PI/RTV or INSTI), 1 prior genotyping M184V determined in historic genotypic resistance tests and last genotyping Primary endpoint: time to virologic failure in M184V-positive vs M184V-negative pts Dual Therapy Initiated, % Pts (N = 436) DRV/RTV + 3TC 36 DTG + 3TC 29 ATV/RTV + 3TC 24 LPV/RTV + 3TC 10 RAL + 3TC 1 Gagliardini R, et al. CROI Abstract 498. Slide credit: clinicaloptions.com

21 M184V and Switch to 3TC-Based Dual ART bayareaaetc.org Slide courtesy M. Gandhi 21

22 Proportion Free From VF M184V and Switch to 3TC-Based Dual ART: Efficacy Estimated Probability of Remaining VF-Free on Dual Therapy* M184V+ overall M184V- overall M184V+ with time of viral suppression 6.6 yrs M184V- with time of viral suppression 6.6 yrs M184V+ with time of viral suppression 3 yrs M184V- with time of viral suppression 3 yrs Yrs From Dual ART Initiation Significantly higher 3-yr probability of remaining free from viral blip without vs with M184V (log-rank P =.016) M184V: 79.8% (95% CI: 67.8% to 91.8%) No M184V: 90.1% (95% CI: 84.0% to 96.2%) *VF: 2 HIV-1 RNA findings > 50 c/ml or 1 finding 200 c/ml. No VF in 21 pts on DTG + 3TC over median f/u of 10 mos. Viral blip: single HIV-1 RNA finding c/ml, not confirmed. Gagliardini R, et al. CROI Abstract 498. Reproduced with permission. Slide credit: clinicaloptions.com

23 Transmitted Drug Resistance in France Aim: estimate the prevalence of transmitted drug resistance associated mutations (TDRAMs) in France in Prevalence of resistance NRTI 5.1% (CI 95%: ) NNRTI 4.0% (CI 95%: ) or 10.2% (CI 95%: ] including ETR/RPV PI 2.8% (CI 95%: ) INI 5.3% (CI 95%: ) L74M n=9, E92Q/G n=2, T97A n=14, E138K n=3, E157Q n=18, S230R n=2, R263K n=2. The double mutant E92Q+T97A was observed in 1 patient bayareaaetc.org Baudier, Abstract

24 Take Home Messages Dual-based therapy with M184V not a good idea (more virologic blips even if not virologic failure, suggesting less robust virological control) Unclear clinical significance of high prevalence of transmitted drug-resistance associated mutations (2nd gen NNRTI and INSTI) but potentially concerning bayareaaetc.org 24

25 C. OPPORTUNISTIC INFECTIONS bayareaaetc.org 25

26 ACTG A5279: 1 month of INH/Rifapentine for LTBI 3000 HIV-infected adults high prevalence country IGRA+ or TST+ 54% female median CD % on ART 80% suppressed Only EFV or NVP based ART 33 vs 32 TB cases 0.67 vs cases/100 pt years Daily INH/RFP x 1 mth non-inferior to INH x 9 mths Randomized INHx9mo INH/RFPx1mo Slide 26 of 46 Slide courtesy T. Wilkins, IAS bayareaaetc.org Chaisson, Abstract 37LB

27 INSPIRING: DTG BID + 2 NRTIs For ART-Naive Pts Receiving Rifampin-Based TB Therapy Interim analysis of open-label, randomized, noncomparative, active-controlled phase IIIb study Primary endpoint: Wk 48 HIV-1 RNA < 50 c/ml (modified FDA snapshot, ITT-E) Pts from South Africa, Brazil, Peru, Mexico, Russia, Argentina, and Thailand Randomization Wk 24 Wk 48 ART-naive pts with HIV-1 RNA 1000 c/ml and CD4+ cell count 50 cells/mm 3 and RIFsensitive TB coinfection (N = 113) DTG 50 mg BID + 2 NRTIs (n = 69) EFV 600 mg QD + 2 NRTIs (n = 44) DTG 50 mg QD + 2 NRTIs (n = 69) TB treatment (all pts) HRZE (2 mos)* HR (4 mos) *TB treatment containing RIF could be started up to 8 wks before randomization and no later than screening (28 to 14 days prior to randomization). DTG dose switch to occur 2 wks after TB treatment completed. Dooley KE, et al. CROI Abstract 33. Slide credit: clinicaloptions.com

28 INSPIRING: Efficacy and PK Outcomes Virologic Outcome at Wk 24, n (%) HIV-1 RNA < 50 copies/ml HIV-1 RNA 50 copies/ml No virologic data DTG + 2 NRTIs (n = 69) EFV + 2 NRTIs (n = 69) 56 (81) 39 (89) 7 (10) 3 (7) 6 (9) 2 (5) Wk n DTG Concentration (Geometric Mean), ng/ml (90% CI, %CV) DTG 50 mg BID + RIF (TB Treatment Phase) ( , 118) ( , 276) DTG 50 mg QD (Post-TB Treatment Phase) ( , 151) ( , 359) Dooley KE, et al. CROI Abstract 33. Slide credit: clinicaloptions.com

29 Pharmacokinetics of Twice Daily BIC/FTC/TAF Plus Rifampin Open-label, parallel-design, multiple-dose, single-center phase I study in which BIC pharmacokinetics were assessed in healthy volunteers who received BIC/FTC/ TAF* QD or BIC/FTC/TAF* BID + RIF 600 mg QD for 28 days (N = 52) Mean BIC PK (% CV) Cohort 1 BIC/FTC/TAF QD (n = 26) Cohort 2 BIC/FTC/TAF BID + RIF QD (n = 26) GLSM Ratio (90% CI) AUC 0-24, ng*h/ml 115,200 (21) 45,600 (23) 39.5 ( ) C max, ng/ml 8530 (16) 4560 (19) 53.2 ( ) C trough, ng/ml 3070 (28) 608 (30) 19.7 ( ) Coadministration of BIC/FTC/TAF BID + RIF resulted in ~ 80% reduction in BIC C trough and ~ 60% reduction in daily BIC exposure This combination is not recommended *BIC/FTC/TAF dosed 50/200/25 mg. Custodio JM, et al. CROI Abstract 34. Slide credit: clinicaloptions.com

30 Pharmacokinetic Study of Effect of Rifampin Coadministration on TAF Exposure Open-label, single-arm phase I PK study of effect of RIF coadministration on TAF PK (N = 21 evaluable healthy volunteers) Dosing: Days 1-28, FTC/TAF 200/25 mg QD; Days 29-56, FTC/TAF 200/25 mg QD + RIF 600 mg QD; Days 57-84, TDF 300 mg QD Intracellular TFV AUC higher for FTC/TAF + RIF vs TDF alone despite RIF decreasing TAF plasma and intracellular TFV AUC Intracellular TFV-DP PK Parameters Geometric mean (95% CI, CV) FTC/TAF + RIF FTC/TAF GM Ratio (90% CI) TDF FTC/TAF + RIF GM Ratio (90% CI) C max fmol*h/ ( , 69%) AUC 0-24 fmol*h/ ( , 82%) C 24h fmol*h/ ( , 87%) 8082 ( , 64%) ( , 102%) 6138 ( , 58%) 0.62 ( ) 0.64 ( ) 0.57 ( ) 1135 ( , 82%) 4994 ( ) ( , 70%) ( , 82%) 851 ( , 71%) 3529 ( , 87%) 0.23 ( ) 0.24 ( ) 0.24 ( ) Cerrone M, et al. CROI Abstract 28LB. Slide credit: clinicaloptions.com

31 Interaction of rifampin and tenofovir alafenamide TFV-DP levels 36% lower with TAF+RIF compared to TAF alone TFV-DP levels with TAF+RIF much higher than TDF alone Slide 31 of 46 Slide courtesy T. Wilkins, IAS bayareaaetc.org Cerrone, Abstract 28LB

32 bayareaaetc.org Slide courtesy M. Gandhi

33 TB APPRISE: Main Findings No difference in maternal toxicities (6-7% hepatotoxicity in both arms), BUT bayareaaetc.org Slide courtesy M. Gandhi

34 Take Home Messages Daily INH/Rifapentine for LTBI could be considered in patients on Efaverinz-based ART regimen but existing alternatives may still be preferred Do NOT use Bictegravir with Rifampin If co-administering Dolutegravir and Rifampin, may need to increase dose to BID, studies ongoing Intracellular drug levels with TAF/FTC and Rifampin coadministration are ok, studies ongoing to look at serum TFV levels During pregnancy, treat active TB but wait until delivery for LTBI treatment bayareaaetc.org 34

35 D. COMPLICATIONS bayareaaetc.org 35

36 Platelet Substudy of Study 1717: Switch From ABC/3TC to FTC/TAF Substudy of randomized, double-blind phase III study in which pts with stable virologic suppression on ABC/3TC + third agent randomized to continue ABC/3TC or switch to FTC/TAF* (N = 556; substudy n = 61) [1,2] Rationale: ABC shown in some studies to be associated with increased CVD risk; increased platelet aggregation associated with CVD [3] GPVI is a collagen receptor that promotes platelet aggregation; platelet activation causes shedding of GPVI, resulting in sgpvi in plasma; sgpvi associated with CV events [4] SWIFT randomized trial showed persistently lower sgpvi levels in virologically suppressed pts who continued ABC/3TC vs those who switched to FTC/TDF [5] Current study compared changes in GPVI and platelet reactivity in pts switched from ABC- to TAF-containing ART or continuing baseline ABCcontaining regimen *Original third agent continued in both arms. 1. Winston A, et al. Lancet HIV. 2018;[Epub ahead of print]. 2. Mallon PW, et al. CROI Abstract Worm SW, et al. J Infect Dis. 2010;201: Al-Tamimi M, et al. Stroke. 2011;42: O Halloran J, et al. AIDS. 2018;[Epub ahead of print]. Slide credit: clinicaloptions.com

37 Mean Change in sgpvi (%) Platelet Function With Switch to FTC/TAF vs Continuing ABC/3TC Platelet reactivity lower with FTC/TAF vs continued ABC/3TC based on higher EC 50 for response to: ADP (P =.03) and TRAP (P =.004) at Wk 4 Collagen at Wk 4 (P =.005) and Wk 12 (P =.02) Median platelet surface GPVI expression significantly higher with FTC/TAF vs continued ABC/3TC at Wk 12 (P =.03) Switch to FTC/TAF associated with higher sgpvi levels persisting through Wk FTC/TAF, n = ABC/3TC, n = FTC/TAF Wk ABC/3TC Mallon PW, et al. CROI Abstract O80. Mallon PW, et al. CROI Abstract 677LB. Reproduced with permission. Slide credit: clinicaloptions.com

38 D:A:D: Serious Clinical Events in Pts With HIV and CKD D:A:D analysis of SCE following CKD diagnosis Included pts with BL creatinine assessment in 2004 with available egfr data (N = 2467) Incident CKD: egfr 60 ml/min/1.73 m 2 (confirmed 3 mos apart) or 25% decrease in egfr when BL egfr 60 ml/min/1.73 m 2 Centrally validated SCE included CVD (MI, stroke, CV procedures), ESRD, ESLD, ADM, NADM, other AIDS events (excludes malignancies), death Excluded recurrent SCE when same type Pts followed to first occurrence of incident SCE, 6 mos after last visit, or February 1, 2016 Ryom L, et al. CROI Abstract O75. Slide credit: clinicaloptions.com

39 Pts With SCE (%) Serious Clinical Events in Pts With HIV and CKD: Time to Event and Incidence Kaplan-Meier Time to SCE Following CKD Time Point Any-SCE Rate, % 12 mos 7.9 ( ) 36 mos 19.8 ( ) Any SCE Death NADM CVD Other AIDS ESRD ESLD ADM Mos After CKD Descriptive analysis performed to determine crude SCE rates in pts followed from first egfr to SCE Parameter Pts Without CKD* (n = 34,116) Pts With CKD* (n = 2460) PYFU 272, Median f/u, yrs (IQR) Pts with any SCE, n (%) Incidence per 1000 PYFU 8.8 ( ) 2.1 ( ) 6300 (18.5) 467 (18.9) 23.0 ( ) 63.7 ( ) *Descriptive population had different inclusion and exclusion criteria than other analyses. Ryom L, et al. CROI Abstract O75. Reproduced with permission. Slide credit: clinicaloptions.com

40 Serious Clinical Events in Pts With HIV and CKD: Risk Factors Population Attributable Fraction > 5% of Key Risk Factors for SCE Following CKD BMI < 18 egfr < 30 ml/min Dyslipidemia Poor HIV control Diabetes Current smoking 5.7% ( ) 13.7% ( ) 9.9% (-8.6 to 23.9) 19.3% ( ) 13.5% ( ) 11.8% ( ) 6.4% ( ) 11.0% ( ) 8.1% ( ) 6.5% (0-10.2) 6.1% ( ) 34.9% ( ) Death CVD Other AIDS events NADM Population Attributable Fraction of Key Risk Factors (%) Ryom L, et al. CROI Abstract O75. Reproduced with permission. Slide credit: clinicaloptions.com

41 Effect of switch from TDF to TAF +/- bisphosphonates Pooled data from TAF switch studies BP use not additive with TAF switch, especially at the hip for unclear reasons. Can consider a sequential strategy of TAF switch followed by BP, but there are no data. Slide 41 of 46 Slide courtesy T. Wilkins, IAS bayareaaetc.org Brown, Abstract 724

42 Take Home Messages More convincing evidence for biological mechanism and reason for elevated CVD risk with recent (but not cumulative) ABC exposure Controversial topic but argues for re-consideration of use of ABC in patients with acute stroke/mi &/or elev CV risk High morbidity and mortality in HIV patients with CKD, but modifiable risk factors (viral control, BMI, smoking, etc) No additive effect of concomitant TDF to TAF switch + bisphosphonates on bone mineral density bayareaaetc.org 42

43 THANK YOU QUESTIONS? bayareaaetc.org 43