Tratamiento óptimo del SIDA con FTC/TAF tras aprobaciones farmacéuticas., Diapositivas de Historia Clínica

¡Descarga Tratamiento óptimo del SIDA con FTC/TAF tras aprobaciones farmacéuticas. y más Diapositivas en PDF de Historia Clínica solo en Docsity! HIV Alert: Best Practices in ART Following Recent Drug Approvals This program is supported by independent educational grants from Gilead Sciences and ViiV Healthcare. Slide credit: clinicaloptions.com About These Slides  Please feel free to use, update, and share some or all of these slides in your noncommercial presentations to colleagues or patients  When using our slides, please retain the source attribution:  These slides may not be published, posted online, or used in commercial presentations without permission. Please contact permissions@clinicaloptions.com for details Slide credit: clinicaloptions.com Program Overview  Indications and Supporting Data for FTC/TAF  How FTC/TAF Compares With Other NRTI Backbones  Expert Perspective – When I’ll Use FTC/TAF… and When I Won’t Slide credit: clinicaloptions.com FTC/TAF Recently FDA Approved  Label information: – Indicated in combination with other ARVs for the treatment of HIV infection – Not recommended for pts with CrCl < 30 mL/min – No dose adjustment necessary CrCl ≥ 30 mL/min; FTC/TDF requires dose adjustment CrCl 30-49 mL/min – Not indicated for PrEP or for pts coinfected with HBV – Dose: FTC 200 mg, TAF 25 mg  Joins other approved TAF-containing fixed-dose combinations – EVG/COBI/FTC/TAF – RPV/FTC/TAF FTC/TAF [package insert]. April 2016. FTC/TDF [package insert]. April 2016. Clinical Trials Supporting FTC/TAF Use Study Pt Population Treatment GS-104/111[1] Treatment naive(N = 1733) Pts randomized to EVG/COBI/FTC/TAF* or EVG/COBI/FTC/TDF GS-109[2] Virologically suppressed on TDF-based regimen (N = 1436) Pts switched to EVG/COBI/FTC/TAF* or remained on TDF-based regimen GS-1089[3] Virologically suppressed on FTC/TDF + third ARV (N = 663) Pts switched to FTC/TAF† + continued third ARV or remained on FTC/TDF + third ARV GS-112[4] Virologically suppressed on varied regimens; stable eGFRCG 30-69 mL/min (N = 242) Pts switched to EVG/COBI/FTC/TAF* Slide credit: clinicaloptions.com 1. Sax PE, et al. Lancet. 2015;385:2606-2615. 2. Mills A, et al. Lancet Infect Dis. 2016;16:43-52. 3. Gallant JE, et al. Lancet HIV. 2016;3:e158-e165. 4. Pozniak A, et al. J Acquir Immune Defic Syndr. 2016;71:530-537. *EVG/COBI/FTC/TAF dosing: 150/150//200/10 mg. †FTC/TAF dosing: 200/10 mg with boosted PIs; 200/25 mg with unboosted third drug. TAF Associated With Improved BMD vs TDF  GS-104/111[1]: smaller declines in spine and hip BMD associated with starting EVG/COBI/FTC/TAF vs EVG/COBI/FTC/TDF at Wk 48 (P < .0001)  GS-109[2] and GS-1089[3]: switching to FTC/TAF-based treatment improved spine and hip BMD vs remaining on FTC/TDF-based treatment at Wk 48 Slide credit: clinicaloptions.com 1. Sax PE, et al. Lancet. 2015;385:2606-2615. 2. Mills A, et al. Lancet Infect Dis. 2016;16:43-52. 3. Gallant JE, et al. Lancet HIV. 2016;3:e158-e165. Spine4 2 0 M ea n % C h an g e in B M D ( 95 % C I) 1.5 -0.2 P < .001 BL Wk 24 Wk 48 Hip4 2 0 1.1 -0.2 BL Wk 24 Wk 48 GS-1089: Mean % BMD Change From BL FTC/TAF FTC/TDF P < .001 Lipid Increases Greater With TAF Than TDF  TAF lacks lipid-lowering effects of TDF but does not have negative impact on lipids  Similar lipid effects observed in GS-109[2] and GS-1089[3] Slide credit: clinicaloptions.com GS-104/111: Median Lipid Changes in Treatment-Naive Pts[1] 1. Sax PE, et al. Lancet. 2015;385:2606-2615. 2. Mills A, et al. Lancet Infect Dis. 2016;16:43-52. 3. Gallant JE, et al. Lancet HIV. 2016;3:e158-e165. 200 150 100 50 0 5 4 3 2 1 0 189 160 177 163 115 101 109 104 51 44 44 48 114 95 108 100 3.7 3.6 3.7 3.6 TC:HDL Ratio P = .84 Triglycerides P = .027 HDL P < .001 LDL P < .001 TC P < .001 EVG/COBI/FTC/TAF Wk 48 Baseline EVG/COBI/FTC/TDF Wk 48 Baseline M ed ia n V al u es ( m g /d L ) GS-112: Switching to EVG/COBI/FTC/TAF in Pts With Renal Impairment  Multicenter, single-arm, open-label phase III trial in which virologically suppressed pts with stable eGFRCG 30-69 mL/min switched to EVG/COBI/FTC/TAF (N = 242) – Varied preswitch regimens: 65% received TDF Pozniak A, et al. J Acquir Immune Defic Syndr. 2016;71:530-537. Slide credit: clinicaloptions.com Clinically Relevant ProteinuriaMeasured GFR by Iohexol Clearance 100 80 60 40 20 0 m G F R (m L /m in ) BL < 50 mL/min BL ≥ 50 mL/min BL Wk 2/4/8 Wk 24 47 43 44 65 65 67 BL Wk 2/4/8 Wk 24 100 80 60 40 20 0 P ts ( % ) Proteinuria (UPCR) ≤ 200 mg/g BL Wk 48 BL Wk 48 > 200 mg/g 56 75 65 91 44 25 35 9 BL < 50 mL/min BL ≥ 50 mL/min Comparing NRTI Backbones (009 Slide credit: clinicaloptions.com Considerations With NRTI Backbones and Associated Regimens NRTIs Considerations ABC/3TC  DTG/ABC/3TC* only STR including unboosted INSTI  Mixed data on CVD risk with ABC in high-risk pts  Cannot be used in HLA-B*5701–positive pts  Not recommended for pts with CrCl < 50 mL/min FTC/TDF  STRs: EVG/COBI/FTC/TDF,* EFV/FTC/TDF, RPV/FTC/TDF  Potential for renal toxicity and proximal tubulopathy  EVG/COBI/FTC/TDF should not be initiated in pts with CrCl < 70 mL/min; discontinue in pts with CrCl < 50 mL/min  EFV/FTC/TDF or RPV/FTC/TDF: not for use in pts with CrCl < 50 mL/min  FTC/TDF must be dose adjusted when CrCl 30-49 mL/min  Potential for decreases in BMD  Lipid-lowering effects FTC/TAF  STRs: EVG/COBI/FTC/TAF* and RPV/FTC/TAF  Comparable efficacy and improved renal and bone profiles vs FTC/TDF  No dose adjustment necessary when CrCl ≥ 30 mL/min *DHHS guideline–recommended initial regimen. References in slidenotes. Expert Perspective: Selecting Therapy in the New Treatment Landscape Slide credit: clinicaloptions.com Should TDF-Based Regimens Still Be Considered as Initial Therapy?  EFV/FTC/TDF remains effective, economical, convenient choice for many pts in resource- constrained settings DHHS ART Guidelines. January 2016. DHHS-Recommended First-line Regimens With TAF Replacements INSTI based  DTG/ABC/3TC  RAL + FTC/TAF  DTG + FTC/TAF  EVG/COBI/FTC/TAF Boosted PI based  DRV/RTV + FTC/TAF Slide credit: clinicaloptions.com If DTG Is Your Preferred INSTI, How Do You Choose DTG/ABC/3TC vs DTG + FTC/TAF? Consideration Potential Choice DTG/ABC/3TC DTG + FTC/TAF Pt might benefit from STR vs MTR (adherence or preference)  Pt has high CVD risk  Pt is HLA-B*5701 positive  Pt has osteopenia or osteoporosis   Pt has renal impairment *  *DTG/ABC/3TC not recommended for pts with CrCl < 50 mL/min as 3TC dose adjustment required. DTG/ABC/3TC [package insert]. September 2015. FTC/TAF [package insert]. April 2016. Slide credit: clinicaloptions.com Opinion: For Which Pts Will I Always/ Never Use TAF-Based Therapy?  Always/usually – Pts with high CVD risk  Relative contraindications – Pts with potential COBI drug interactions (EVG/COBI/FTC/ TAF) – Pt receiving PPIs or H2 blockers (RPV/FTC/TAF) – Pt with CD4+ cell count < 200 c/mm3 (RPV/FTC/TAF)  Never/unlikely – Pt with CrCl < 30 mL/min – Pt with severe hepatic impairment (EVG/COBI/FTC/ TAF) – Pt with HIV-1 RNA > 100,000 copies/mL (RPV/FTC/TAF) – Pt receiving rifamycin – Pregnant pt – As PrEP References in slidenotes.