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Fármacos para VIH/SIDA y sus efectos colaterales

Fármacos para VIH/SIDA y sus efectos colaterales

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  • This slide lists the faculty who were involved in the production of these slides.
  • ART, antiretroviral therapy
  • AE, adverse events; ITT, intention-to-treat analysis; NC = F, noncompleters = failure analysis; PP, per-protocol analysis; SAE, serious adverse events For detailed information on this study, go to: http://clinicaloptions.com/HIV/Conference%20Coverage/IAS%202013/New%20Data/Capsules/WELBB01.aspx
  • For detailed information on this study, go to: http://clinicaloptions.com/HIV/Conference%20Coverage/IAS%202013/New%20Data/Capsules/WELBB02.aspx
  • For detailed information on this study, go to: http://clinicaloptions.com/HIV/Conference%20Coverage/IAS%202013/New%20Data/Capsules/WELBB02.aspx
  • For detailed information on this study, go to: http://clinicaloptions.com/HIV/Conference%20Coverage/IAS%202013/New%20Data/Capsules/WELBB02.aspx
  • For detailed information on this study, go to: http://clinicaloptions.com/HIV/Conference%20Coverage/IAS%202013/New%20Data/Capsules/WEAB0104.aspx
  • For detailed information on this study, go to: http://clinicaloptions.com/HIV/Conference%20Coverage/IAS%202013/New%20Data/Capsules/WEAB0104.aspx
  • DOT, directly observed therapy; pys, person years.
  • ART, antiretroviral therapy; BID, twice daily; DRV, darunavir; OBR, optimized background regimen; QD, once daily. For detailed information on this study, go to: http://clinicaloptions.com/HIV/Conference%20Coverage/IAS%202013/New%20Data/Capsules/WELBB03.aspx
  • For detailed information on this study, go to: http://clinicaloptions.com/HIV/Conference%20Coverage/IAS%202013/New%20Data/Capsules/WELBB03.aspx
  • For detailed information on this study, go to: http://clinicaloptions.com/HIV/Conference%20Coverage/IAS%202013/New%20Data/Capsules/WEAB0103.aspx
  • IM, intramuscular; LD, loading dose; SC, subcutaneous. For detailed information on this study, go to: http://clinicaloptions.com/HIV/Conference%20Coverage/IAS%202013/New%20Data/Capsules/WEAB0103.aspx
  • For detailed information on this study, go to: http://clinicaloptions.com/HIV/Conference%20Coverage/IAS%202013/New%20Data/Capsules/WEAB0103.aspx
  • BID, twice daily; BMD, bone mineral density; DXA, dual-energy x-ray absorptiometry; QD, once daily For detailed information on this study, go to: http://clinicaloptions.com/HIV/Conference%20Coverage/IAS%202013/New%20Data/Capsules/WELBB05.aspx
  • BMD, bone mineral density; BMI, body mass index. For detailed information on this study, go to: http://clinicaloptions.com/HIV/Conference%20Coverage/IAS%202013/New%20Data/Capsules/WELBB05.aspx
  • For detailed information on this study, go to: http://clinicaloptions.com/HIV/Conference%20Coverage/IAS%202013/New%20Data/Capsules/WEAB0205.aspx
  • For detailed information on this study, go to: http://clinicaloptions.com/HIV/Conference%20Coverage/IAS%202013/New%20Data/Capsules/TUAB0101.aspx

Cco ias 2013_new_data Presentation Transcript

  • 1. June 30 – July 3, 2013 Kuala Lumpur, Malaysia Highlights of IAS 2013 CCO Official Conference Coverage of the 7th IAS Conference on HIV Pathogenesis, Treatment and Prevention This program is supported by educational grants from
  • 2. clinicaloptions.com/hiv HIV/AIDS Update From IAS 2013 About These Slides  Users are encouraged to use these slides in their own noncommercial presentations, but we ask that content and attribution not be changed. Users are asked to honor this intent  These slides may not be published or posted online without permission from Clinical Care Options (email permissions@clinicaloptions.com) Disclaimer The materials published on the Clinical Care Options Web site reflect the views of the authors of the CCO material, not those of Clinical Care Options, LLC, the CME providers, or the companies providing educational grants. The materials may discuss uses and dosages for therapeutic products that have not been approved by the United States Food and Drug Administration. A qualified healthcare professional should be consulted before using any therapeutic product discussed. Readers should verify all information and data before treating patients or using any therapies described in these materials.
  • 3. clinicaloptions.com/hiv HIV/AIDS Update From IAS 2013 Faculty Andrew Carr, MBBS, MD, FRACP, FRCPA Professor of Medicine University of New South Wales Director, HIV, Immunology, and Infectious Diseases Unit St Vincent’s Hospital Sydney, Australia Joel E. Gallant, MD, MPH Adjunct Professor of Medicine Division of Infectious Diseases Johns Hopkins University School of Medicine Associate Medical Director of Specialty Services Southwest CARE Center Santa Fe, NM Anton L. Pozniak, MD, FRCP Consultant Physician Director of HIV Services Department of HIV and Genitourinary Medicine Chelsea and Westminster Hospital NHS Trust London, United Kingdom
  • 4. clinicaloptions.com/hiv HIV/AIDS Update From IAS 2013 Disclosures Andrew Carr, MBBS, MD, FRACP, FRCPA, has disclosed that he has received funds for research support from Gilead Sciences and Merck Sharp & Dohme; has served as a consultant for Gilead Sciences, Merck Sharp & Dohme, and ViiV Healthcare; has served on advisory boards for Gilead Sciences, Merck Sharp & Dohme, and ViiV Healthcare; and has received lecture and travel sponsorships from Gilead Sciences, Merck Sharp & Dohme, Roche, and ViiV Healthcare. Joel E. Gallant, MD, MPH, has disclosed that he has received consulting fees from Bristol Myers Squibb, Gilead Sciences, Janssen, Merck, and‐ Takara Bio and funds for research support from Gilead Sciences. Anton L. Pozniak, MD, FRCP, has disclosed that he has received funds for research support and consulting fees from Bristol-Myers Squibb, Gilead Sciences, Janssen, Merck Sharp & Dohme, and ViiV Healthcare and has participated in company sponsored speaker’s bureau for Gilead Sciences.
  • 5. Antiretroviral Therapy in Resource-Constrained Settings
  • 6. clinicaloptions.com/hiv HIV/AIDS Update From IAS 2013 WHO 2013: Updated Treatment Guidelines for Adults, Adolescents, and Children  Expanded ART eligibility – Treatment initiation threshold: CD4+ ≤ 500 cells/mm3 – Prioritize severe or advanced HIV or CD4+ ≤ 350 cells/mm3  Viral load testing preferred for monitoring ART  Preferred initial regimen: fixed-dose TDF + 3TC (or FTC) + EFV – Discontinue use of d4T due to toxicity WHO Consolidated Treatment Guidelines. June 2013.
  • 7. clinicaloptions.com/hiv HIV/AIDS Update From IAS 2013  Randomized, double-blind, placebo-controlled, noninferiority phase III trial – Part of ongoing effort to identify ARVs effective at lower doses (and cost)  No significant difference in SAEs between treatment arms  More pts with AEs for EFV 600 mg vs EFV 400 mg (47.2% vs 36.8%; P = .008)  More pts discontinued EFV 600 mg due to AE vs EFV 400 mg (1.9% vs 5.8%; P = .010) ENCORE1: 400-mg EFV Noninferior to 600-mg EFV With TDF/FTC for Initial ART Puls R, et al. IAS 2013. Abstract WELBB01. EFV* 400 mg + placebo + TDF/FTC 300/200 mg (n = 324) EFV* 600 mg + TDF/FTC 300/200 mg (n = 312) ART-naive pts, CD4+ 50-500 cells/mm3 , HIV-1 RNA > 1000 copies/mL (N = 636) Wk 48 Stratified by clinical site and HIV-1 RNA at screening (< 100,000 or ≥ 100,000 copies/mL) *EFV administered as 200-mg tablets. HIV-1 RNA < 200 c/mL at Wk 48, % NC = F 90.0 85.8
  • 8. clinicaloptions.com/hiv HIV/AIDS Update From IAS 2013 EARNEST: Second-Line LPV/RTV-Based ART After Initial NNRTI Failure  Randomized, controlled, open-label, phase III trial  Baseline demographics (medians): HIV-1 RNA 69,782 copies/mL; CD4+ 71 cells/mm3 ; time on ART, 4 yrs Paton N, et al. IAS 2013. Abstract WELBB02. WHO, World Health Organization. *Including clinical, CD4+ cell count (viral load confirmed), or virologic criteria. † Selected by physician according to local standard of care. HIV-infected adults and adolescents, received first-line NNRTI-based ART > 12 mos, > 90% adherence in previous mo, treatment failure by WHO (2010) criteria* (N = 1277) LPV/RTV + 2-3 NRTIs† (n = 426) LPV/RTV + RAL (n = 433) LPV/RTV + RAL (n = 418) Wk 144Wk 12 LPV/RTV monotherapy (n = 418)
  • 9. clinicaloptions.com/hiv HIV/AIDS Update From IAS 2013 EARNEST: Clinical Outcomes at Wk 96  “Good disease control” at Wk 96 defined as pt alive, no new WHO 4 events from Wks 0-96, and CD4+ cell count > 250 cells/mm3 , and HIV-1 RNA < 10,000 copies/mL or > 10,000 copies/mL without PI resistance mutations Paton N, et al. IAS 2013. Abstract WELBB02. 100 80 60 40 20 0 Good Disease Control HIV-1 RNA < 400 copies/mL HIV-1 RNA < 50 copies/mL PI/NRTI PI/RAL PI Mono60 64 56 86 86 61 74 73 44
  • 10. clinicaloptions.com/hiv HIV/AIDS Update From IAS 2013 EARNEST: Other Outcomes  LPV/RTV monotherapy arm discontinued due to inferior virologic suppression, higher frequency of LPV resistance  No significant difference in 96-wk resistance rates between LPV/RTV + NRTIs and LPV/RTV + RAL  Similar rates of grade 3/4 AEs across treatment arms (range: 22% to 24%) Paton N, et al. IAS 2013. Abstract WELBB02.
  • 11. Current Antiretroviral Agents
  • 12. clinicaloptions.com/hiv HIV/AIDS Update From IAS 2013 Meta-analysis of Efficacy of Initial ART Regimens in Prospective Trials  Meta-analysis of 216 treatment arms from prospective trials of initial ART, 1994-2010 (N = 40,124 pts)  Mean rate of undetectable HIV-1 RNA: 60% overall – 66% at Wk 48, 60% at Wk 96, 52% at Wk 144 – 25% discontinued before end of study  Better mean efficacy with more recent year of initiation – 43% in 1994 vs 78% in 2010 Lee FJ, et al. IAS 2013. Abstract WEAB0104.
  • 13. clinicaloptions.com/hiv HIV/AIDS Update From IAS 2013 Efficacy of Initial ART Associated With NRTI Backbone, Third Drug, Other Factors  Mean efficacy 70% vs 62% with baseline VL < vs ≥ 100,000 copies/mL  Mean efficacy 75% vs 65% with DHHS “preferred” vs “alternative” ART  Number of pills or doses per day did not predict overall efficacy  Specific NRTI backbones, third drugs associated with efficacy Lee FJ, et al. IAS 2013. Abstract WEAB0104. Efficacy, % (SD) Coefficient (95% CI) P Value NRTI backbone TDF/FTC 73 (10) Ref ABC/3TC 63 (7) -7.6 (-12.7 to -2.6) .003 Third drug class NNRTI 61 (15) Ref INSTI 84 (5) 11.9 (4.6-19.2) .002 Boosted PI 67 (9) -0.9 (-4.7 to 3.0) .660 Adjusted for multivariable analysis including year of commencement, other drugs received, baseline patient characteristics, and duration of follow-up.
  • 14. clinicaloptions.com/hiv HIV/AIDS Update From IAS 2013 Efficacy of EVG/COBI/TDF/FTC vs EFV/TDF/FTC When Adherence < 95%  Preplanned adherence analysis at Wk 96 of Study GS-US-236-0102  ≥ 90% adherence in 93% with EVG/COBI/TDF/FTC, 89% with EFV/TDF/FTC  Significantly greater improvement in CD4+ cell counts with EVG/COBI/TDF/FTC vs EFV/TDF/FTC (317 vs 245; P = .039) ART-naive pts, HIV RNA ≥ 5000 copies/mL, no CD4+ restrictions, eGFR ≥ 70 mL/min (N = 700) EVG/COBI/TDF/FTC QD + EFV/TDF/FTC placebo (n = 348) EFV/TDF/FTC QHS + EVG/COBI/TDF/FTC placebo (n = 352) Wk 96 Stratified by HIV RNA ≤ 100,000 or > 100,000 copies/mL Shalit P, et al. IAS 2013. Abstract TUPE293. ≥ 95% Adherence < 95% Adherence 88 74 89 63 VL < 50 copies/mL at Wk 96
  • 15. clinicaloptions.com/hiv HIV/AIDS Update From IAS 2013 Bangkok Study: Directly Observed PrEP With TDF Reduces HIV Acquisition in IDUs  Phase III, randomized, double-blind, placebo-controlled trial – HIV-uninfected IDUs (N = 2,413) received TDF or placebo – DOT at drug treatment clinics between 2005 and 2010  Significantly fewer new infections with TDF vs placebo (0.35/100 pys vs 0.68/100 pys; P = .01) – Overall efficacy: 49% – Detectable TDF at study end: 74%  Higher adherence associated with greater efficacy  Safety and tolerability similar to other TDF-containing PrEP trials Choopanya K, et al. IAS 2013. Abstract WELBC05.
  • 16. clinicaloptions.com/hiv HIV/AIDS Update From IAS 2013 Bangkok TDF Study: Adherence to PrEP and Risk of HIV Acquisition Choopanya K, et al. IAS 2013. Abstract WELBC05. 100 80 60 40 20 0 UninfectedPts(%) mITT > 67% > 75% > 90% > 95% > 97.5% Adherence Pts Uninfected By Level of Adherence 49 54 58 68 72 84
  • 17. Investigational Antiretroviral Agents
  • 18. clinicaloptions.com/hiv HIV/AIDS Update From IAS 2013 SAILING: Dolutegravir vs Raltegravir in ART-Exp’d, Integrase Inhibitor–Naive Pts  Phase III randomized, double-blind, double-dummy, noninferiority study Treatment-experienced, integrase inhibitor–naive patients with HIV-1 RNA > 400 copies/mL and ≥ 2 class resistance (N = 715) Dolutegravir 50 mg QD + OBR (n = 354) Raltegravir 400 mg BID + OBR (n = 361) Stratified by number of fully active background agents, use of DRV, screening HIV-1 RNA ≤ vs > 50,000 copies/mL Wk 48 Cahn P, et al. IAS 2013. Abstract WELBB03.
  • 19. clinicaloptions.com/hiv HIV/AIDS Update From IAS 2013 SAILING: Superior Rate of Virologic Suppression With DTG vs RAL at Wk 48  Lower incidence of resistance at VF with DTG vs RAL – Integrase resistance: 1% vs 5% – OBR resistance: 1% vs 3%  Both regimens well tolerated with similar AE profiles – Grade 2-4: 8% vs 9% – Discontinuations: 3% vs 4%  No difference in outcome between study arms when combined with fully active DRV/RTV Cahn P, et al. IAS 2013. Abstract WELBB03. 100 80 60 40 20 0 PercentageofSubjects(%) Virologic success Virologic nonresponse No Wk 48 data DTG + OBR RAL + OBR 71 64 20 28 9 9 Δ 7.4 (95% CI, 0.7-14.2); P = .03
  • 20. clinicaloptions.com/hiv HIV/AIDS Update From IAS 2013 Long-Acting GSK1265744 and TMC278  Nanosuspensions: drug nanocrystals suspended in liquid – Increased drug dissolution rate – Nanocrystal design allows for low injection volume  Potential utility as long-acting injections for ART regimens, PrEP – GSK1265744 (DTG analogue) dosed monthly or quarterly – TMC278 nanosuspension of RPV dosed monthly Spreen W, et al. IAS 2013. Abstract WEAB0103.
  • 21. clinicaloptions.com/hiv HIV/AIDS Update From IAS 2013 GSK744 200 mg IM GSK744 200 mg IM GSK744 400 mg IM GSK744 400 mg IM Monthly Oral Lead-in* Day 1 Wk 4 Wk 8 Wk 12 Wk 16 Wk 20 Wk 24 Cohort 1 (n = 10) Cohort 2 (n = 10) Cohort 3 (n = 10) Quarterly Cohort 4 (n = 10) TMC278 (LD† ) 1200 mg IM TMC278 900 mg IM TMC278 (LD† ) 1200 mg IM TMC278 600 mg IM All cohorts followed for 52 wks after last injection (ongoing) Coadministration of Long-Acting GSK1265744 and TMC278  Randomized, open-label, repeated-dose phase I trial in healthy adults Spreen W, et al. IAS 2013. Abstract WEAB0103. *Oral lead-in: GSK744 30 mg/day for 14 days, then 7-day washout. † Loading dose given as split injection dose (2 x 2 mL). GSK744 800 mg IM (LD† ) GSK744 800 mg IM (LD† ) GSK744 800 mg IM (LD† ) GSK744 200 mg SC GSK744 200 mg SC GSK744 200 mg SC GSK744 200 mg IM GSK744 400 mg IM GSK744 800 mg IM GSK744 800 mg IM (LD† )
  • 22. clinicaloptions.com/hiv HIV/AIDS Update From IAS 2013 Favorable Drug Concentrations With GSK1265744 and TMC278 Injections  PK results – GSK1265744 injected every 4 wks or every 12 wks achieved plasma levels > protein-adjusted IC90 – TMC278 dosed every 4 wks achieved plasma levels comparable to those achieved by oral RPV 25 mg/day in HIV-infected patients  GSK1265744 safe, well tolerated alone and in combination with TMC278  Findings support phase II study of GSK1265744 + TMC278 as 2-drug ART regimen Spreen W, et al. IAS 2013. Abstract WEAB0103.
  • 23. Adverse Events and Comorbidities
  • 24. clinicaloptions.com/hiv HIV/AIDS Update From IAS 2013 SECOND-LINE Subanalysis: BMD Loss With LPV/RTV + NRTIs vs LPV/RTV + RAL  Subanalysis of randomized, open-label, multicenter, international trial Martin A, et al. IAS 2013. Abstract WELBB05. LPV/RTV 400/100 mg BID + RAL 400 mg BID (n = 108) LPV/RTV 400/100 mg BID + 2-3 NRTIs QD or BID (n = 102) HIV-infected patients with virologic failure on first-line regimen of NNRTI + 2 NRTIs (N = 211 consented to BMD substudy) DXA scan at Wk 48 DXA scan at Wk 0
  • 25. clinicaloptions.com/hiv HIV/AIDS Update From IAS 2013 SECOND-LINE: Greater Mean BMD Loss With NRTI-Based Regimen at Wk 48  No significant difference in frequency of new osteopenia, osteoporosis  Greater decline in lumbar spine BMD associated with lower BMI, no TDF before study, and TDF initiation on study Martin A, et al. IAS 2013. Abstract WELBB05. 0 -1 -3 -4 -6 Mean%Change(SE)inBMD FromBaselinetoWk48,% -2 -5 Proximal Femur Lumbar Spine -5.2 -2.9 -4.2 -2 P = .0001 P = .0006 LPV/RTV + 2-3 NRTIs LPV/RTV + RAL
  • 26. clinicaloptions.com/hiv HIV/AIDS Update From IAS 2013 HIV Independently Associated With Increased Risk of Hip Fractures  Population-based cohort study SIDIAPQ database, 2007-2009; Catalonia, Spain (N = 1,118,587 pts aged ≥ 40 yrs) – HIV-infected: 2489 (0.22%) – Identified incident major osteoporotic and hip fractures  HIV infection associated with – 4.72-fold ↑ hazard ratio for hip fracture – 1.75-fold ↑ hazard ratio for all fractures – Independent of age, sex, BMI, smoking, EtOH use Knobel H, et al. IAS 2013. Abstract WEAB0205. 5.0 4.5 3.5 2.5 1.5Age-SpecificHipFractureIncidence per1000Person-Yrs 4.0 2.0 1.0 0.5 0 3.0 Age (yrs) 40-45 45-50 50-55 55-60 60-65 65-70 70-75 75-80 HIV-infected HIV-noninfected
  • 27. clinicaloptions.com/hiv HIV/AIDS Update From IAS 2013 NVP Cutaneous Reactions Reduced By HLA-B*35:05 and CCHCR1 Screening  CCHCR1 and HLA-B*35:05 associated with rash[1,2] – HLA-B*35:05 uncommon except Southeast Asian and South Americans  Prospective, randomized, multicenter, controlled trial[3] – N = 1103 assigned to screening vs no screening – All started NVP-based therapy EXCEPT pts screened positive started EFV-based therapy Group Relative Risk P Value Overall, screened vs unscreened 0.68 .020 Sex Male Female 0.84 0.55 .491 .016 CD4+ count, cells/mm3 < 250 > 250 0.64 0.88 .027 .740 1. Chantarangsu S et al. Pharmacogenet Genomics. 2009;19:139-146. 2. Chantarangsu S et al. Clin Infect Dis 2011;53:341-348. 3. Kiertiburanakul S, et al. IAS 2013. Abstract WELBB04.  Lower incidence of cutaneous AEs in screened group – 13.2% vs 18.0%
  • 28. clinicaloptions.com/hiv HIV/AIDS Update From IAS 2013 High HCV Reinfection Rate Among HIV-Infected MSM  Single-site, retrospective study (2004-2012) of HIV- infected MSM at London clinic – Cleared prior HCV infection spontaneously or after HCV treatment  Reinfection rates similar in pts with prior spontaneous clearance vs SVR Martin T, et al. IAS 2013. Abstract TUAB0101. P = .15 HCVReinfectionIncidenceper100Person-Yrs 7.8 9.6 4.2 23.2 0 5 10 15 20 25 30 35 40 45 50 Overall Reinfection Rate Reinfection Posttreatment Reinfection After Spontaneous Clearance Second Reinfection Rate Following SVR or Clearance of First Reinfection
  • 29. Go Online for More CCO Coverage of IAS 2013 Capsule Summaries of key studies selected by the faculty Expert Highlights audio podcasts by expert faculty clinicaloptions.com/ias2013