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Avances del tratamiento aannttiirrrreettrroovviirraall
Avances del tratamiento aannttiirrrreettrroovviirraall
Antirretrovirales disponibles en la actualidad 
Nucleoside RTIs 
• Zidovudine (ZDV) 
• Didanosine (ddI) 
• Zalcitabine (dd...
Antirretrovirales acutales y futuros 
Nucleoside RTIs 
• Zidovudine (ZDV) 
• Didanosine (ddI) 
• Zalcitabine (ddC) 
• Stav...
MK-1439 (Doravirine): A New NNRTI 
MMKK--11443399 2255 mmgg 
Dose-Ranging Trial in Treatment-naïve Patients 
 3-fold poten...
Virologic Response by Screening RNA 
Ad hoc analysis (Week 24), Observed Failure 
≤100,000 c/mL 100,000 c/mL 
All MK = 86%...
Virologic Response by Screening RNA 
Ad hoc analysis (Week 24), Observed Failure 
≤100,000 c/mL 100,000 c/mL 
All MK = 86%...
La coformulación de Darunavir pronto será 
posible
Avances del tratamiento aannttiirrrreettrroovviirraall
GSK1265744 (744) 
 HIV-1 integrase inhibitor, 
dolutegravir analogue 
 Oral drug (t½ = 40 hours) 
 Long-acting SC or IM in...
LATTE Study Design 
 Phase IIb, randomized, multicenter, partially blind, dose-ranging study 
 744 + NRTI subjects with a ...
Primary Endpoint 
Virologic Success: HIV-1 RNA 50 c/mL by FDA Snapshot (ITT-E) 
Induction Phase Maintenance Phase 
Week 
7...
Avances del tratamiento aannttiirrrreettrroovviirraall
Choice of Initial Regimen 
Tenofovir/emtricitabine (TDF/FTC) OR 
Abacavir/lamivudine (ABC/3TC) 
WITH 
Third agent (NNRTI, ...
A5257 Study Design* 
HIV-infected patients, ≥18 yr, with no previous ART, 
VL ≥ 1000 c/mL at US Sites 
Randomized 1:1:1 to...
ACTG 5257: Failure Comparisons at 96 Weeks 
Virologic Failure 
Arms Difference 97.5% CI Favors 
ATV/r vs. RAL 3.4% -0.7%, ...
ACTG 5257: Failure Comparisons at 96 Weeks 
Virologic Failure 
Arms Difference 97.5% CI Favors 
ATV/r vs. RAL 3.4% -0.7%, ...
ACTG 5257: Failure Comparisons at 96 Weeks 
Virologic Failure 
Arms Difference 97.5% CI Favors 
ATV/r vs. RAL 3.4% -0.7%, ...
Avances del tratamiento aannttiirrrreettrroovviirraall
Elvitegravir/c: Eficacia y seguridad en los estudios 102 y 103 
en semana 96 
TDF/FTC/EVG/c (n=701) EFV/TDF/FTC (n=352) AT...
Dolutegravir (estudio SPRING-2). Análisis de eficacia a 48 semanas 
• DTG es no-inferior a RAL con un margen del 10%: Dife...
Snapshot por estrato de randomización 
DTG 
50 mg QD 
DRV/r 
800 mg/ 
100 mg QD 
en la semana 48 
A favor 
DRV/r 
A favor ...
SINGLE Study. Virologic Suppression (HIV-1 RNA 50 
c/mL; FDA Snapshot) 
DTG: 80% 
EFV: 72% 
Week 96 adjusted difference in...
Resistance Mutations in Individuals Who Met PDVF 
Criteria 
TE = treatment emergent 
*n=1 with K101E, n=1 with K103N, n=2 ...
Avances del tratamiento aannttiirrrreettrroovviirraall
Evolución del tratamiento antirretroviral de 
inicio 
Dual 
NRTIs 
Dual 
therapy 
• IP/r + NRTI 
• IP/r + NNRTI 
• IP/r + ...
NEAT 001/ANRS 143 
NEAT 001/ANRS 143 study design 
• Phase III, randomised, open-label, multicenter, parallel-group, non-i...
100 
80 
60 
40 
0 
NEAT 001/ANRS 143 
Percentage of participants with available data 
91 % 93 % 
89 % 
0 4 8 12 18 24 32 ...
NEAT 001/ANRS 143 Renal safety 
Creatinine clearance (eGFR, ml/min [Cockroft-Gault formula] 
Mean (95% CI) change from bas...
Estudio Gardel: LPV/r + 3TC 
GGAARRDDEELL:: DDeessiiggnn 
– Phase III, randomized, international , controlled, open-label ...
Estudio Gardel: LPV/r + 3TC 
GGAARRDDEELL:: VViirraall llooaadd 5500 ccooppiieess//mmLL aatt wweeeekk 4488 ((IITTTTee)) 
C...
GARDEL: Viral load 50 copies/mL at week 48 (ITTe), baseline VL  
100.000 copies/mL) 
(p= 0.145, difference +9.3% 
[CI95%:-...
Avances del tratamiento aannttiirrrreettrroovviirraall
STRATEGY - PI 
Study Design 
Multicenter, randomized, open-label, 96-week study 
n =293 
n =140 
STRATEGY-PI 
• HIV-1 RNA ...
STRATEGY - PI 
PI and Number of Prior Regimens at Randomization 
Reasons subject choose to enroll in study 
Desire to simp...
95% CI for Difference 
Favors 
E/C/F/TDF 
0.4 13.7 
12% 
Favors 
STRATEGY - PI 
Primary Endpoint: HIV-1 RNA  50 c/mL 
E/C/...
STRATEGY – PI 
Patient Reported Outcomes 
% of Subject Reporting Symptoms 
HIV Symptom Index 
Diarrhea 
100 
126 
284 
132...
STRATEGY - NNRTI 
Study Design 
Multicenter, randomized, open-label, 96-week study 
n =291 
n =143 
STRATEGY-NNRTI 
• HIV-...
Single-tablet Regimen 
(n =338; 78%) 
Atripla (n =322; 74%) 
Complera (n =16; 4%) 
STRATEGY - NNRTI 
NNRTI and Number of P...
95% CI for Difference 
Favors 
E/C/F/TDF 
-0.5 12.0 
12% 
Favors 
STRATEGY - NNRTI 
Primary Endpoint: HIV-1 RNA  50 c/mL 
...
STRATEGY – NNRTI: Efavirenz Subgroup 
Patient Reported Outcomes 
% of Subject Reporting Symptoms 
HIV Symptom Index 
Vivid...
Avances del tratamiento aannttiirrrreettrroovviirraall
Study 
Effect size (CI) 
TDF/FTC oral-PrEP in MSM 
(iPrEx, Grant et al 2010) 
Medical male circumcision 
(MMC) (Orange Far...
Partner Cohort Study 
 Estudio en 1.140 parejas serodiscordantes, 40% HSH. 
 Criterios para incluir en el estudio 
– Manif...
Avances del tratamiento aannttiirrrreettrroovviirraall
Consenso sobre el inicio del tratamiento: 
Recomendaciones de GESIDA 2014
Consenso sobre el inicio del tratamiento: 
Recomendaciones de la DHHS 
Recuento 
de CD4 
(cél/mm3) 
DHHS 2013 
350 TAR rec...
Avances del tratamiento aannttiirrrreettrroovviirraall
Avances del tratamiento aannttiirrrreettrroovviirraall
OBJETIVOS 
o Analizar la valoración que los pacientes con VIH en España hacen 
de las diferentes características del trata...
MÉTODO 
DISEÑO Encuesta transversal 
MUESTRA 370 personas con VIH 
PROCEDIMIENT 
O 
Recogida datos en 6 hospitales: 
-Mutu...
DATOS SANITARIOS 
MEDIANA 12 
AÑOS
IMPORTANCIA CARACTERISTICAS TRATAMIENTO 
PARA ADHERENCIA
IMPORTANCIA CARACTERISTICAS TRATAMIENTO 
PARA ADHERENCIA
IMPORTANCIA CARACTERISTICAS TRATAMIENTO 
PARA ADHERENCIA
IMPORTANCIA CARACTERISTICAS TRATAMIENTO 
PARA ADHERENCIA (FACTORES)
Avances del tratamiento aannttiirrrreettrroovviirraall
LIMITACIONES PARA ESTOS AVANCES 
61
VIH. novedades terapéuticas
VIH. novedades terapéuticas
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VIH. novedades terapéuticas

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Presentación realizada por Piedad Arazo Garcés, en el curso de la Jornada Pacientes y Salud: “Foros en el CIBA”. Novedades terapéuticas e importancia del paciente informado, el 12 de noviembre de 2014.

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VIH. novedades terapéuticas

  1. 1. X
  2. 2. Avances del tratamiento aannttiirrrreettrroovviirraall
  3. 3. Avances del tratamiento aannttiirrrreettrroovviirraall
  4. 4. Antirretrovirales disponibles en la actualidad Nucleoside RTIs • Zidovudine (ZDV) • Didanosine (ddI) • Zalcitabine (ddC) • Stavudine (d4T) • Lamivudine (3TC) • Abacavir (ABC) • Emtricitabine (FTC) • Tenofovir DF (TDF) Nonnucleos(t)ide RTIs • Nevirapine (NVP) • Rilpivirina (RPV) • Efavirenz (EFV) • Etravirine (ETR) Protease Inhibitors • Saquinavir (SQV) • Ritonavir (RTV) • Indinavir (IDV) • Nelfinavir (NFV) • Amprenavir (APV) • Lopinavir/r (LPV/r) • Atazanavir (ATV) • Fosamprenavir (Fos-APV) • Tipranavir (TPV) Boosters • Darunavir (DRV) • Ritonavir (RTV) Fusion Inhibitor • Enfuvirtide (T-20) CCR5 Antagonist • Maraviroc (MVC) Integrase Inhibitors • Raltegravir (RAL) • Elvitegravir
  5. 5. Antirretrovirales acutales y futuros Nucleoside RTIs • Zidovudine (ZDV) • Didanosine (ddI) • Zalcitabine (ddC) • Stavudine (d4T) • Lamivudine (3TC) • Abacavir (ABC) • Emtricitabine (FTC) • Tenofovir DF (TDF) • Tenofovir AF (TAF) Nonnucleos(t)ide RTIs • Nevirapine (NVP) • Rilpivirina (RPV) • Efavirenz (EFV) • Etravirine (ETR) • Doravirine (DRV) Protease Inhibitors • Saquinavir (SQV) • Ritonavir (RTV) • Indinavir (IDV) • Nelfinavir (NFV) • Amprenavir (APV) • Lopinavir/r (LPV/r) • Atazanavir (ATV) • Fosamprenavir (Fos-APV) • Tipranavir (TPV) Boosters • Darunavir (DRV) • Ritonavir (RTV) • Cobicistat* (cobi) Fusion Inhibitor • Enfuvirtide (T-20) CCR5 Antagonist • Maraviroc (MVC) Integrase Inhibitors • Raltegravir (RAL) • Elvitegravir •Dolutegravir*
  6. 6. MK-1439 (Doravirine): A New NNRTI MMKK--11443399 2255 mmgg Dose-Ranging Trial in Treatment-naïve Patients 3-fold potency shift vs. common NNRTI-resistance mutants K103N, Y181C, G190A, E138K(4) Low potential for CNS effects, drug-drug interactions; lower protein-binding vs. other NNRTIs Morales-Ramirez J, et al. 21st CROI; Boston, MA; March 3-6, 2014. Abst. 92LB. EEffaavviirreennzz MMKK--11443399 220000 mmgg EEffaavviirreennzz 96 Week End of Study Treatment for Part 1 MK-1439 Selected Dose PART 1 Dose-Ranging ~200 patients (~40/group) MMKK--11443399 5500 mmgg MMKK--11443399 110000 mmgg 24 Week Primary Time Point for Dose Selection
  7. 7. Virologic Response by Screening RNA Ad hoc analysis (Week 24), Observed Failure ≤100,000 c/mL 100,000 c/mL All MK = 86% All MK = 92% All MK = 66% All MK = 94% 27 12 13 11 12 Copyright © 2014 Merck Co. Inc. All Rights Reserved.
  8. 8. Virologic Response by Screening RNA Ad hoc analysis (Week 24), Observed Failure ≤100,000 c/mL 100,000 c/mL All MK = 86% All MK = 92% All MK = 66% All MK = 94% 27 12 13 11 12 Copyright © 2014 Merck Co. Inc. All Rights Reserved.
  9. 9. La coformulación de Darunavir pronto será posible
  10. 10. Avances del tratamiento aannttiirrrreettrroovviirraall
  11. 11. GSK1265744 (744) HIV-1 integrase inhibitor, dolutegravir analogue Oral drug (t½ = 40 hours) Long-acting SC or IM injection (apparent t½ ≈ 40 days) Good virologic response at 5 and 30 mg/day as oral 10-day monotherapy Margolis et al. CROI 2014; Boston, MA. Abstract 91LB. Spreen et al. HIV Clin Trials. 2013;14:192-203.
  12. 12. LATTE Study Design Phase IIb, randomized, multicenter, partially blind, dose-ranging study 744 + NRTI subjects with a W20 HIV-1 RNA 50 c/mL simplified to 744 + RPV at W24 HIV ART-naive HIV-1 RNA ≥1000 c/mL CD4 ≥200 cells/mm3 1:1:1:1 Randomization Stratified by VL and NRTI *ABC/3TC or TDF/FTC Oral Induction Phase 744 10 mg + 2 NRTIs* 744 30 mg + 2 NRTIs 744 60 mg + 2 NRTIs Oral Maintenance Phase 744 10 mg + RPV 25 mg 744 30 mg + RPV 25 mg 744 60 mg + RPV 25 mg EFV 600 mg + 2 NRTIs Week Primary endpoint: % HIV-1 RNA 50 c/mL at 48 weeks (FDA “Snapshot”) – Intent-to-treat exposed (ITT-E) – received at least one dose of Investigational Product (IP) – Intent-to-treat maintenance exposed (ITT-ME) – received at least one maintenance dose
  13. 13. Primary Endpoint Virologic Success: HIV-1 RNA 50 c/mL by FDA Snapshot (ITT-E) Induction Phase Maintenance Phase Week 744 overall response W48 82% EFV response W48 71% 744 overall response W24 87% EFV response W24 74% Median (IQR) change from baseline CD4+ cell count (cells/mm3) Week 48 744 overall +219 (141,343) EFV +227 (134,369) Proportion, % BL 2 4 8 12 16 24 2628 32 36 40 48 Margolis et al. CROI 2014; Boston, MA. Abstract 91LB.
  14. 14. Avances del tratamiento aannttiirrrreettrroovviirraall
  15. 15. Choice of Initial Regimen Tenofovir/emtricitabine (TDF/FTC) OR Abacavir/lamivudine (ABC/3TC) WITH Third agent (NNRTI, boosted PI, or InSTI): • Efavirenz OR • Atazanavir/r OR • Darunavir/r OR • Raltegravir Thompson et al, JAMA, 2012.
  16. 16. A5257 Study Design* HIV-infected patients, ≥18 yr, with no previous ART, VL ≥ 1000 c/mL at US Sites Randomized 1:1:1 to Open Label Therapy Stratified by screening HIV-1 RNA level (≥ vs 100,000 c/mL), A5260s metabolic substudy participation, cardiovascular risk RRAALL 440000 mmgg BBIIDD ++ FFTTCC//TTDDFF220000//330000mmggQQDD DDRRVV 880000mmggQQDD++RRTTVV 110000mmggQQDD ++ FFTTCC//TTDDFF 220000//330000 mmgg QQDD AATTVV 330000mmgg QQDD ++ RRTTVV 110000mmggQQDD ++ FFTTCC//TTDDFF 220000//330000 mmgg QQDD Study Conclusion 96 weeks after final participant enrolled Follow-up continued for 96 weeks after randomization of last subject (range 2-4 years) regardless of status on randomized ART 600 PACIENTES POR RAMA *With the exception of RTV, all ART drugs were provided by the study
  17. 17. ACTG 5257: Failure Comparisons at 96 Weeks Virologic Failure Arms Difference 97.5% CI Favors ATV/r vs. RAL 3.4% -0.7%, 7.4% Equivalent DRV/r vs. RAL 5.6% 1.3%, 9.9% Equivalent ATV/r vs. DRV/r -2.2% -6.7%, 2.3% Equivalent
  18. 18. ACTG 5257: Failure Comparisons at 96 Weeks Virologic Failure Arms Difference 97.5% CI Favors ATV/r vs. RAL 3.4% -0.7%, 7.4% Equivalent DRV/r vs. RAL 5.6% 1.3%, 9.9% Equivalent ATV/r vs. DRV/r -2.2% -6.7%, 2.3% Equivalent Tolerability Failure Arms Difference 97.5% CI Favors ATV/r vs. RAL 13% 9.4%, 16% RAL Superior DRV/r vs. RAL 3.6% 1.4%, 5.8% RAL Superior ATV/r vs. DRV/r 9.2% 5.5%, 13% DRV/r Superior
  19. 19. ACTG 5257: Failure Comparisons at 96 Weeks Virologic Failure Arms Difference 97.5% CI Favors ATV/r vs. RAL 3.4% -0.7%, 7.4% Equivalent DRV/r vs. RAL 5.6% 1.3%, 9.9% Equivalent ATV/r vs. DRV/r -2.2% -6.7%, 2.3% Equivalent Tolerability Failure Arms Difference 97.5% CI Favors ATV/r vs. RAL 13% 9.4%, 16% RAL Superior DRV/r vs. RAL 3.6% 1.4%, 5.8% RAL Superior ATV/r vs. DRV/r 9.2% 5.5%, 13% DRV/r Superior Cumulative Failure Arms Difference 97.5% CI Favors ATV/r vs. RAL 15% 10%, 20% RAL Superior DRV/r vs. RAL 7.5% 3.2%, 12% RAL Superior ATV/r vs. DRV/r 7.5% 2.3%, 13% DRV/r Superior
  20. 20. Avances del tratamiento aannttiirrrreettrroovviirraall
  21. 21. Elvitegravir/c: Eficacia y seguridad en los estudios 102 y 103 en semana 96 TDF/FTC/EVG/c (n=701) EFV/TDF/FTC (n=352) ATV/r + FTC/TDF (n=355) 80 80 85 81 82 82 100 80 60 40 20 • Subgrupo de CD4 50 (n=30). • 11/19 EVGc con éxito virológico. 8 fueron fracasos (todos con CV 100 K c/mL, 4 con adherencia subóptima. • 5/6 EFV con éxito virológico; 1 fracaso (CV 100 K c/mL, con adherencia subóptima). • 5/5 ATV/r + TDF/FTC con éxito virológico. Zolopa A. et al. 20th CROI. Atlanta, 3 – 6 Marzo 2013. #553 78 84 86 0 50 a ≤200 200 a ≤350 350 CD4 (cels/mm3) Éxito virológico en semana 96 (%)
  22. 22. Dolutegravir (estudio SPRING-2). Análisis de eficacia a 48 semanas • DTG es no-inferior a RAL con un margen del 10%: Diferencia: 2,5%; IC95% (-2,2% a 7,1%). • No-inferioridad demostrada con 100.000 c/mL 7,5 (-3,1 a 18). • No-inferioridad demostrada con TDF/FTC: 4,6 (-1,3 a 10,6) y con ABC/3TC -0,8 (-8,2 a 6,6). • Similar recuperación de CD4 entre DTG y RAL (+230 CD4 a las 48 semanas). • Fallo virológico a 48 semanas: DTG 20 (5%; 1 con CV400); RAL: 28 (7%; 5 con CV400). • Resistencias: con DTG: 0 a integrasa, 0 a nucleósidos; RAL: 1 a integrasa, 4 a nucleósidos. • Efectos adversos grado 2-4: 6% DTG vs 7% RAL. Abandonos por EA: 2% DTG, vs 2% RAL. • Incremento de creatinina (grado 1/2): 2%/0,6% para DTG vs 2%/0% para RAL. Raffi F, et al. IAS 2012. Washington DC. 19 - 27 Julio. #THLBB04 100 90 80 70 60 50 40 30 20 10 0 BL Sem 4 Sem 8 Sem 12 Sem 16 Sem 24 Sem 32 Sem 40 Sem 48 Semana Proporción 50 c/mL (%) DTG 50 mg QD RAL 400 mg BID DTG 88% RAL 85%
  23. 23. Snapshot por estrato de randomización DTG 50 mg QD DRV/r 800 mg/ 100 mg QD en la semana 48 A favor DRV/r A favor DTG Globala n=484 90% 83% HIV-1 RNA basalb ≤100.000 c/mL 100.000 c/mL n=362 n=122 88% 93% 87% 70% Nucleósidosb ABC/3TC TDF/FTC n=159 n=325 90% 90% 85% 81% Estudio FLAMINGO: DTG vs DRV/r en pacientes naïve Proporción (IC 95%) de individuos con RNA VIH-1 50 c/mL en el tiempo-snapshot 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% DTG: 90% 0,9 7,113,2 *Diferencia ajustada (DTG-DRV/r) basada en un análisis estratificado CMH ajustando por HIV RNA basal y los nucleósidos acompañantes. Resultados confirmados en el análisis por protocolo: 91% DTG vs. 84% DRV/r, Δ (IC): 7,4 (1,4 – 13,3). -40-30-20-10 0 10 20 30 40 50 Diferencia en la proporción (DGT – DRV/r) Feinberg J. et al. ICAAC. Denver, 10-13 Septiembre 2013. #1464a 0% Proporción (%) BL 4 8 12 16 24 Semanas 36 48 DTG 50 mg QD DRV/r 800 mg/100 mg QD DRV/r: 83% 95% IC para la diferencia* A favor DRV/r A favor DTG -20% -12% 0 20% Test de superioriad: P=0,025 Se demostró superioridad global 60 aDiferencia ajustada (DTG-DRV/r) basada en un análisis estratificado Cochran-Mantel- Haenszel ajustando por HIV RNA basal y los nucleósidos acompañantes. . bLas diferencias no ajustadas apoyan la no-inferioridad de DTG vs DRV/r en los estratos de HIV-1 RNA basal y de nucleósidos acompañantes.
  24. 24. SINGLE Study. Virologic Suppression (HIV-1 RNA 50 c/mL; FDA Snapshot) DTG: 80% EFV: 72% Week 96 adjusted difference in response (95% CI): +8.0% (+2.3% to +13.8%); P=0.006 4 8 1216 24 32 40 48 60 72 84 96 Walmsley et al. CROI 2014; Boston, MA. Poster 543.
  25. 25. Resistance Mutations in Individuals Who Met PDVF Criteria TE = treatment emergent *n=1 with K101E, n=1 with K103N, n=2 with K103K/N, n=1 with G190A and n=1 with K103N + G190A **E157Q/P polymorphism detected with no significant change in IN phenotypic susceptibility Walmsley et al. CROI 2014; Boston, MA. Poster 543. Mutation DTG + ABC/3TC QD (n=414) EFV/TDF/FTC QD (n=419) NRTI TE major mutations 0 1 (K65R) NNRTI TE major mutations 0 6 (K101E, K103N, G190A)* INI-r TE major substitution 0** 0
  26. 26. Avances del tratamiento aannttiirrrreettrroovviirraall
  27. 27. Evolución del tratamiento antirretroviral de inicio Dual NRTIs Dual therapy • IP/r + NRTI • IP/r + NNRTI • IP/r + CCR5 inh • IP/r + II 1987 Zidovudine: ••First First NRTI NRTI 1991–2 ddI and ddC approved 1991–2 ddI and ddC approved 1994 Dual Dual NRTIs NRTIs better better than than monotherapy monotherapy Triple Triple combination combination therapy therapy • NNRTI + 2NRTIs • IP/r + 2NRTIs • II + 2NRTIs • CCR5 i + 2 NRTIs Dual therapy Sequential monotherapy
  28. 28. NEAT 001/ANRS 143 NEAT 001/ANRS 143 study design • Phase III, randomised, open-label, multicenter, parallel-group, non-inferiority, strategic trial • 78 sites, 15 countries (Austria, Belgium, Denmark, France, Germany, Great Britain, Greece, Hungary, Ireland, Italy, Netherlands, Poland, Portugal, Spain, Sweden) DRV+r 800+100 mg QD + RAL 400 mg BID DRV+r 800+100 mg QD + TDF/FTC FDC QD Minimum Week 96 HIV-1 ART-naïve ≥ 18 years HIV-1 RNA 1000 c/ml CD4 ≤ 500/mm3 HBs Ag negative No major IAS-USA resistance mutations • Randomisation 1:1 • stratified by country and participation in virology/immunology substudy • Composite virological and clinical primary endpoint (6 components)
  29. 29. 100 80 60 40 0 NEAT 001/ANRS 143 Percentage of participants with available data 91 % 93 % 89 % 0 4 8 12 18 24 32 48 64 80 96 401 404 385 389 377 385 382 387 376 388 356 374 RAL + DRV/r TDF/FTC + DRV/r 20 Weeks 89 % HIV-1 RNA 50 c/ml n Mean (95% CI) Change From Baseline CD4+ Cell Count (cells/mm3) W48 W96 RAL + DRV/r + 197 (184, 210) + 267 (250, 285) TDF/FTC + DRV/r + 193 (180, 206) + 266 (249, 283)
  30. 30. NEAT 001/ANRS 143 Renal safety Creatinine clearance (eGFR, ml/min [Cockroft-Gault formula] Mean (95% CI) change from baseline 5 0 -5 -10 -15 + 0.9 0 4 8 12 18 24 32 48 64 80 96 Weeks RAL + DRV/r TDF/FTC + DRV/r No grade 2-4 creatinine elevation in either arm - 3.8 p=0.02
  31. 31. Estudio Gardel: LPV/r + 3TC GGAARRDDEELL:: DDeessiiggnn – Phase III, randomized, international , controlled, open-label study – Study included adult patients from Argentina, Chile, Mexico, Peru, Spain, US. Cahn P, et al. EACS, 2013. Brussels, Belgium. Wk 24 interim analysis DT: LPV/r 400/100mg BID + 3TC 150 mg BID (n=217) TT: LPV/r 400/100mg BID + 3TC or FTC and a third investigator-selected NRTI in fixed-dose combination (n=209) Stratified by screening HIV-1 RNA (≤ or 100,000 copies/mL) ARV- naive patients, ³18 years HIV-1 RNA 1000 copies/ml No IAS-USA defined NRTI or PI resistance at screening* HB(s)Ag negative (N = 426) Wk 48 primary endpoint *Defined as 1 major or 2 minor LPV/r mutations) LPV major mutations include the following mutations: V32I; I47V/A; L76V; V82A/F/T/S
  32. 32. Estudio Gardel: LPV/r + 3TC GGAARRDDEELL:: VViirraall llooaadd 5500 ccooppiieess//mmLL aatt wweeeekk 4488 ((IITTTTee)) Cahn P, et al. EACS, 2013. Brussels, Belgium. (p= 0.171, difference +4.6% [CI95%:-2.2% to +11.8%])
  33. 33. GARDEL: Viral load 50 copies/mL at week 48 (ITTe), baseline VL 100.000 copies/mL) (p= 0.145, difference +9.3% [CI95%:-2.8% to +21.5%]) Cahn P, et al. EACS, 2013. Brussels, Belgium. Estudio Gardel: LPV/r + 3TC
  34. 34. Avances del tratamiento aannttiirrrreettrroovviirraall
  35. 35. STRATEGY - PI Study Design Multicenter, randomized, open-label, 96-week study n =293 n =140 STRATEGY-PI • HIV-1 RNA 50 c/mL for ≥6 months • ≤ 2 prior ARV regimens • No resistance to FTC or TDF • eGFRCG ≥70 mL/min 2:1 E/C/F/TDF (Stribild®) PI + RTV + FTC/TDF PI + RTV + FTC/TDF Week 48 Week 96 Primary endpoint: HIV-1 RNA 50 c/mL at Week 48 by Snapshot (noninferiority margin of 12%). If noninferiority is established, then superiority will be tested. Secondary endpoint: Safety and tolerability at Week 48 96 Other endpoints: Patient reported outcomes* *HIV Symptom Index and HIV Treatment Satisfaction questionnaires E/C/F/TDF: single-tablet regimen elvitegravir 150mg, cobicistat 150mg, emtricitabine 200mg, tenofovir DF 300mg; Stribild® PI + RTV + FTC/TDF: ritonavir-boosted protease inhibitor and emtricitabine/tenofovir DF Study GS-US-236-0115 is registered with ClinicalTrials.gov, number NCT01475838.
  36. 36. STRATEGY - PI PI and Number of Prior Regimens at Randomization Reasons subject choose to enroll in study Desire to simplify current regimen 86% Concerned about long-term side effects of current regimen 12% ATV, atazanavir, DRV, darunavir; FPV, fosamprenavir; LPV, lopinavir; SQV, saquinavir
  37. 37. 95% CI for Difference Favors E/C/F/TDF 0.4 13.7 12% Favors STRATEGY - PI Primary Endpoint: HIV-1 RNA 50 c/mL E/C/F/TDF (n=290) PI + RTV + FTC/TDF (n=139) PI + RTV + FTC/TDF 6.7 -12% 0 Percentage of Subjects (%) 94% 1% 6% 87% 1% 12% 100 90 80 70 60 50 40 30 20 10 0 Virologic Success W48 Virologic Failure W48 No Virologic Data W48 Prespecified sequential testing Statistical superiority (p = 0.025) CD4 Cell Count (cells/mm3) Baseline (mean) ΔWeek 48 (mean) P-value (Δ W48 - BL) E/C/F/TDF 603 +40 0.001 PI + RTV + FTC/TDF 625 +32 =0.025 Full analysis set excluded subjects with protocol-prohibited mutations on historical genotype and those not on PI at randomization.
  38. 38. STRATEGY – PI Patient Reported Outcomes % of Subject Reporting Symptoms HIV Symptom Index Diarrhea 100 126 284 132 222 ** * 77 260 68 211 56 133 63 102 53 116 53 87 108 283 84 223 Bloating Baseline E/C/F/TDF PI + RTV + FTC/TDF 86 264 41 208 PI + RTV + FTC/TDF BL W48 BL W48 BL W48 BL W48 Subjects who switched to E/C/F/TDF from PI + RTV + FTC/TDF had Week 48 E/C/F/TDF 44 134 32 101 48 118 38 87 Lower rates of diarrhea and bloating at Week 48 compared to baseline Higher treatment satisfaction scores at Week 24 (mean: 23 vs. 15, p 0.001)^ 34 100 *P 0.04 **P 0.001 (comparison with baseline within each treatment group). Decreases noted at week 4 sustained to week 48. P 0.001, diarrhea P=0.019, bloating (comparison of changes from baseline at week 48 between treatment group). ^ HIV Treatment Satisfaction questionnaire, score range: -30 to 30
  39. 39. STRATEGY - NNRTI Study Design Multicenter, randomized, open-label, 96-week study n =291 n =143 STRATEGY-NNRTI • HIV-1 RNA 50 c/mL for ≥6 months • ≤ 2 prior ARV regimens • No resistance to FTC or TDF • eGFRCG ≥70 mL/min 2:1 E/C/F/TDF (Stribild®) NNRTI + FTC/TDF NNRTI + FTC/TDF Week 48 Week 96 Primary endpoint: HIV-1 RNA 50 c/mL at Week 48 by Snapshot (noninferiority margin of 12%). If noninferiority established, test for superiority Secondary endpoint: Safety and tolerability at Week 48 96 Other endpoints: Patient reported outcomes* *Expanded HIV Symptom Index and HIV Treatment Satisfaction questionnaires E/C/F/TDF: single-tablet regimen elvitegravir 150mg, cobicistat 150mg, emtricitabine 200mg, tenofovir DF 300mg; Stribild® NNRTI + FTC/TDF: non-nucleoside reverse transcriptase inhibitor and emtricitabine/tenofovir DF Study GS-US-236-0121 is registered with ClinicalTrials.gov, number NCT01495702.
  40. 40. Single-tablet Regimen (n =338; 78%) Atripla (n =322; 74%) Complera (n =16; 4%) STRATEGY - NNRTI NNRTI and Number of Prior Regimens EFV, efavirenz; ETR, etravirine; NNRTI, non-nucleoside reverse transcriptase inhibitors; NVP, nevirapine; RPV, rilpivirine
  41. 41. 95% CI for Difference Favors E/C/F/TDF -0.5 12.0 12% Favors STRATEGY - NNRTI Primary Endpoint: HIV-1 RNA 50 c/mL NNRTI + FTC/TDF 5.3 -12% 0 Percentage of Subjects (%) 93% E/C/F/TDF (n=290) NNRTI + FTC/TDF (n=143) 1% 6% 88% 1% 11% 100 90 80 70 60 50 40 30 20 10 0 Virologic Success W48 Virologic Failure W48 No Virologic Data W48 CD4 Cell Count (cells/mm3) Baseline (mean) ΔWeek 48 (mean) P-value (Δ W48 - BL) E/C/F/TDF 586 +56 0.001 NNRTI + FTC/TDF 593 +58 0.001 The full analysis set excluded subjects with prohibited mutations on historical genotype and those not on NNRTI at randomization.
  42. 42. STRATEGY – NNRTI: Efavirenz Subgroup Patient Reported Outcomes % of Subject Reporting Symptoms HIV Symptom Index Vivid Dreams Insomnia 100 Anxiety Dizziness 136 224 ** * 75 212 65 101 56 87 119 224 * 84 209 48 100 41 87 103 222 71 208 Baseline E/C/FTDF NNRTI + FTC/TDF 40 100 E/C/FTDF NNRTI + FTC/TDF ** Week 48 BL W48 BL W48 BL W48 BL W48 BL W48 BL W48 BL W48 BL W48 Subjects who switched to E/C/F/TDF from EFV + FTC/TDF had 34 87 90 225 49 211 Lower rates of neuropsychiatric symptoms at Week 48 compared to baseline Higher treatment satisfaction scores at Week 24 (mean: 21 vs. 14, p 0.001)^ 37 99 32 87 * P 0.01 **P 0.001 (comparison with baseline within treatment group). Decreases noted at week 4 sustained through week 48. P 0.001, vivid dreams P 0.01, dizziness (comparison of changes from baseline at week 48 between treatment group). ^ HIV Treatment Satisfaction questionnaire, score range: -30 to 30
  43. 43. Avances del tratamiento aannttiirrrreettrroovviirraall
  44. 44. Study Effect size (CI) TDF/FTC oral-PrEP in MSM (iPrEx, Grant et al 2010) Medical male circumcision (MMC) (Orange Farm, Rakai, Kisumu) 44% (15, 63) 57% (42, 68) Prime-boost HIV Vaccine (Thai RV144) 31% (1, 51) 0% 10 20 30 40 50 60 70 80 90 100% Efficacy 1% tenofovir gel (Caprisa 004, Karim et al.) 39% (6, 60) Immediate ART for positive Partners (HPTN052) *Provisional 96% (82, 99)* TDF/FTC oral-PrEP in heterosexuals (TDF2, CDC) TDF oral-PrEP in serodiscordant Partner (Partners PrEP) 63% (22, 83)* TDF/FTC oral-PrEP in serodiscordant Partner (Partners PrEP) 62% (34, 78)* 73% (49, 85)* Profilaxis pre-exposición al VIH
  45. 45. Partner Cohort Study Estudio en 1.140 parejas serodiscordantes, 40% HSH. Criterios para incluir en el estudio – Manifestar que realizaban relaciones sexuales sin preservativo – No seguir estrategias de profilaxis pre-exposición o postexposición Análisis a 767 parejas Al inicio del estudio – Los VIH de las parejas HSH llevan TAR con una media de 5 años – Los VIH de las parejas HTS llevaban TAR entre 7-10 años Se realizaron: 16.400 RS entre los HSH y 28.000 en los HTS – No transmisión del virus dentro de la pareja Riesgo de transmisión con un IC95% del 0,45% anual general y 1% en el caso de las RS anales No son datos definitivos: el estudio finaliza en el año 2017 Author’s Last Name, Conference Name, Year, Presentation # 45
  46. 46. Avances del tratamiento aannttiirrrreettrroovviirraall
  47. 47. Consenso sobre el inicio del tratamiento: Recomendaciones de GESIDA 2014
  48. 48. Consenso sobre el inicio del tratamiento: Recomendaciones de la DHHS Recuento de CD4 (cél/mm3) DHHS 2013 350 TAR recomendado (AI) 350 a 500 TAR recomendado (AII) 500 TAR recomendado (BIII)
  49. 49. Avances del tratamiento aannttiirrrreettrroovviirraall
  50. 50. Avances del tratamiento aannttiirrrreettrroovviirraall
  51. 51. OBJETIVOS o Analizar la valoración que los pacientes con VIH en España hacen de las diferentes características del tratamiento antirretroviral (TARV) o Estudiar el perfil de los pacientes, sus necesidades de información, la relación médico-paciente y su bienestar.
  52. 52. MÉTODO DISEÑO Encuesta transversal MUESTRA 370 personas con VIH PROCEDIMIENT O Recogida datos en 6 hospitales: -Mutua Terrassa (BCN), Miguel Servet (ZGZ), Reina Sofía (Córdoba), Xeral (Vigo), Universitario (La Coruña) VARIABLES (a)Datos socio-demográficos , (b) Datos sanitarios (c) Información sobre el VIH, (d) características TARV, (e) Relación médico-paciente, (f) Bienestar
  53. 53. DATOS SANITARIOS MEDIANA 12 AÑOS
  54. 54. IMPORTANCIA CARACTERISTICAS TRATAMIENTO PARA ADHERENCIA
  55. 55. IMPORTANCIA CARACTERISTICAS TRATAMIENTO PARA ADHERENCIA
  56. 56. IMPORTANCIA CARACTERISTICAS TRATAMIENTO PARA ADHERENCIA
  57. 57. IMPORTANCIA CARACTERISTICAS TRATAMIENTO PARA ADHERENCIA (FACTORES)
  58. 58. Avances del tratamiento aannttiirrrreettrroovviirraall
  59. 59. LIMITACIONES PARA ESTOS AVANCES 61

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