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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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Avances del tratamiento antirretroviralAvances del tratamiento antirretroviral
Avances del tratamiento antirretroviralAvances del tratamiento antirretroviral
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)• Darunavir (DRV)Boosters
• Ritonavir (RTV)Fusion Inhibitor• Enfuvirtide (T-20)
CCR5 Antagonist• Maraviroc (MVC)
Integrase Inhibitors• Raltegravir (RAL)• Elvitegravir
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)• Darunavir (DRV)Boosters
• Ritonavir (RTV)• Cobicistat* (cobi) Fusion Inhibitor
• Enfuvirtide (T-20)
CCR5 Antagonist• Maraviroc (MVC)
Integrase Inhibitors• Raltegravir (RAL)• Elvitegravir•Dolutegravir*
MK-1439 (Doravirine): A New NNRTI
� <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.
EfavirenzEfavirenz
MK-1439 200 mgMK-1439 200 mg
EfavirenzEfavirenz
96 Week End of Study Treatment
for Part 1
96 Week End of Study Treatment
for Part 1
MK-1439 Selected Dose
MK-1439 Selected Dose
PART 1 Dose-Ranging ~200 patients (~40/group)
PART 1 Dose-Ranging ~200 patients (~40/group)
MK-1439 50 mgMK-1439 50 mg
MK-1439 100 mgMK-1439 100 mg
MK-1439 25 mgMK-1439 25 mg
24 Week Primary Time Point for Dose Selection
24 Week Primary Time Point for Dose Selection
Dose-Ranging Trial in Treatment-naïve Patients
Virologic Response by Screening RNAAd hoc analysis (Week 24), Observed Failure
≤100,000 c/mL >100,000 c/mL
27 12 13 1211
Copyright © 2014 Merck & Co. Inc. All Rights Reserved.
All MK = 86% All MK = 92% All MK = 66% All MK = 94%
Virologic Response by Screening RNAAd hoc analysis (Week 24), Observed Failure
≤100,000 c/mL >100,000 c/mL
27 12 13 1211
Copyright © 2014 Merck & Co. Inc. All Rights Reserved.
All MK = 86% All MK = 92% All MK = 66% All MK = 94%
La coformulación de Darunavir pronto seráposible
Avances del tratamiento antirretroviralAvances del tratamiento antirretroviral
� 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
GSK1265744 (744)
Margolis et al. CROI 2014; Boston, MA. Abstract 91LB.
Spreen et al. HIV Clin Trials. 2013;14:192-203.
� Phase IIb, randomized, multicenter, partially blind , dose-ranging study
� 744 + NRTI subjects with a W20 HIV-1 RNA <50 c/mL s implified to 744 + RPV at W24
� 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) – recei ved at least one maintenance dose
LATTE Study Design
*ABC/3TC or TDF/FTC
HIV ART-naive
HIV-1 RNA ≥≥≥≥1000 c/mL
CD4 ≥≥≥≥200 cells/mm3
1:1:1:1 Randomization
Stratified by VL
and NRTI
744 30 mg + 2 NRTIs
744 10 mg + 2 NRTIs*
Oral Induction Phase
744 60 mg + 2 NRTIs
EFV 600 mg + 2 NRTIs
Oral Maintenance Phase
744 10 mg + RPV 25 mg
744 30 mg + RPV 25 mg
744 60 mg + RPV 25 mg
Week
Primary Endpoint Virologic Success: HIV-1 RNA <50 c/mL by FDA Snapsh ot (ITT-E)
Week
744 overall response W4882%
EFV response W4871%
744 overall response W2487%
EFV response W2474%
Median (IQR) change from baseline CD4+ cell count
(cells/mm 3)Week 48
744 overall +219 (141,343)
EFV +227 (134,369)
Pro
po
rtio
n, %
242 4 8 12 16 4032 483626 28BL
Induction Phase Maintenance Phase
Margolis et al. CROI 2014; Boston, MA. Abstract 91LB.
Avances del tratamiento antirretroviralAvances del tratamiento antirretroviral
Choice of Initial Regimen
Tenofovir/emtricitabine (TDF/FTC) ORAbacavir/lamivudine (ABC/3TC)
WITH
Third agent (NNRTI, boosted PI, or InSTI):
• Efavirenz OR
• Atazanavir/r OR
• Darunavir/r OR
• RaltegravirThompson et al, JAMA, 2012.
A5257 Study Design*
RAL 400 mg BID + RAL 400 mg BID +
FTC/TDFFTC/TDF 200/300200/300 mgmg QDQDDRV 800DRV 800 mgmg QDQD ++ RTV 100RTV 100 mgmg QD QD
+ FTC/TDF 200/300 mg QD+ FTC/TDF 200/300 mg QDATV 300ATV 300 mg QD + RTV 100mgmg QD + RTV 100mg QDQD
+ FTC/TDF 200/300 mg QD+ FTC/TDF 200/300 mg QD
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
HIV-infected patients, ≥18 yr, with no previous ART, VL ≥ 1000 c/mL at US Sites
Randomized 1:1:1 to Open Label TherapyStratified by screening HIV-1 RNA level (≥ vs < 100,000 c/mL), A5260s
metabolic substudy participation, cardiovascular risk
*With the exception of RTV, all ART drugs were provided by the study
600 PACIENTES POR RAMA
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
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
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
ACTG 5257: Failure Comparisons at 96 Weeks
Avances del tratamiento antirretroviralAvances del tratamiento antirretroviral
Elvitegravir/c: Eficacia y seguridad en los estudios 102 y 103
en semana 96
• 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
80 80 82 85 81 82
0
20
40
60
80
100
>50 a ≤200 >200 a ≤350 >350
TDF/FTC/EVG/c (n=701) EFV/TDF/FTC (n=352) ATV/r + FTC/TDF (n=355)
CD4 (cels/mm 3)
Éxi
to v
iroló
gico
en
sem
ana
96 (
%)
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 CV>400); RAL: 28 (7%; 5 con CV>400). • 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
Pro
porc
ión
<50
c/m
L (%
)
DTG 50 mg QD
RAL 400 mg BID
DTG 88%
RAL 85%
DTG
50 mg QD
DRV/r
800 mg/
100 mg QD
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
Feinberg J. et al. ICAAC. Denver, 10-13 Septiembre 2013. #1464a
Proporción (IC 95%) de individuos con RNA VIH-1 <50 c/mL en el tiempo-snapshot
Snapshot por estrato de randomizaciónen la semana 48
*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, ∆∆∆∆ (IC): 7,4 (1,4 – 13,3).
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Pro
porc
ión
(%)
BL 4 8 12 16 24Semanas
36 48
DTG 50 mg QD
DRV/r 800 mg/100 mg QD
DRV/r: 83%
DTG: 90%
95% IC para la diferencia *
A favor DRV/r
A favorDTG
0 20%-12%-20%
Test de superioriad: P=0,025
0,9 7,113,2
Se demostró superioridad global
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.
A favor DRV/r
A favor DTG
60
Diferencia en la proporción (DGT – DRV/r)
50403020100-10-20-30-40
SINGLE Study. Virologic Suppression (HIV-1 RNA <50
c/mL; FDA Snapshot)
Walmsley et al. CROI 2014; Boston, MA. Poster 543.
24 32 40 48 60 8472 96161284
Week 96 adjusted difference in response (95% CI): +8.0% (+2.3% to +13.8%); P=0.006
DTG: 80%
EFV: 72%
Resistance Mutations in Individuals Who Met PDVF
Criteria
Walmsley et al. CROI 2014; Boston, MA. Poster 543.
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
MutationDTG + 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
Avances del tratamiento antirretroviralAvances del tratamiento antirretroviral
Evolución del tratamiento antirretroviral de inicio
DualNRTIsDual
NRTIs
• IP/r + NRTI• IP/r + NNRTI• IP/r + CCR5 inh• IP/r + II
1987Zidovudine:•First NRTI
1987Zidovudine:•First NRTI
1991–2ddI and ddC approved
1991–2ddI and ddC approved
1994Dual NRTIs better than monotherapy
1994Dual NRTIs better than monotherapy
• NNRTI + 2NRTIs• IP/r + 2NRTIs• II + 2NRTIs • CCR5 i + 2 NRTIs
Triple
combination
therapy
Triple
combination
therapy
Dual
therapy
Dual
therapySequential
monotherapySequential
monotherapy
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 + TDF/FTC FDC QD
DRV+r 800+100 mg QD + RAL 400 mg BID
Minimum
Week 96• Randomisation 1:1 • stratified by country and participation in virology/immunology substudy
HIV-1 ART-naïve≥≥≥≥ 18 years
HIV-1 RNA > 1000 c/mlCD4 ≤≤≤≤ 500/mm3
HBs Ag negativeNo major IAS-USA resistance mutations
• Composite virological and clinical primary endpoint (6 components)
NEAT 001/ANRS 143
0
0 4 8 12 18 24 32 48 64 80 96
401404
385389
377385
382387
376388
356374
RAL + DRV/r
TDF/FTC + DRV/r
20
40
60
80
100
Weeks
Percentage of participants with available data
89 %
91 % 93 %
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)
NEAT 001/ANRS 143
Creatinine clearance (eGFR, ml/min [Cockroft-Gault formula]Mean (95% CI) change from baseline
No grade 2-4 creatinine elevation in either arm
-15
-10
-5
0
5
0 4 8 12 18 24 3232 48 64 80 96
Weeks
RAL + DRV/r TDF/FTC + DRV/r
- 3.8
+ 0.9
p=0.02
NEAT 001/ANRS 143Renal safety
– Phase III, randomized, international , controlled, open-label study
– Study included adult patients from Argentina, Chile, Mexico, Peru, Spain, US.
GARDEL: DesignGARDEL: Design
Cahn P, et al. EACS, 2013. Brussels, Belgium.
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)
ARV- naive patients,
≥18 years
HIV-1 RNA
>1000 copies/ml
No IAS-USA defined NRTI
or PI resistance at
screening*
HB(s)Ag negative
(N = 426)
Stratified by screening
HIV-1 RNA
(≤ or > 100,000 copies/mL)
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
Wk 24
interim analysis
Estudio Gardel: LPV/r + 3TC
GARDEL: GARDEL: Viral load <50 copies/mL at week 48 (ITTe)Viral load <50 copies/mL at week 48 (ITTe)
Cahn P, et al. EACS, 2013. Brussels, Belgium.
(p= 0.171, difference +4.6%
[CI95%:-2.2% to +11.8%])
Estudio Gardel: LPV/r + 3TC
(p= 0.145, difference +9.3%
[CI95%:-2.8% to +21.5%])
GARDEL: Viral load <50 copies/mL at week 48 (ITTe), baseline VL >
100.000 copies/mL)
Cahn P, et al. EACS, 2013. Brussels, Belgium.
Estudio Gardel: LPV/r + 3TC
Avances del tratamiento antirretroviralAvances del tratamiento antirretroviral
Multicenter, randomized, open-label, 96-week study
n =293
n =140• 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
PI + RTV + FTC/TDF
E/C/F/TDF (Stribild®)PI + RTV + FTC/TDF
Week 96Week 48
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*
STRATEGY-PI
*HIV Symptom Index and HIV Treatment Satisfaction questionnairesE/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 DFStudy GS-US-236-0115 is registered with ClinicalTrials.gov, number NCT01475838.
STRATEGY - PI
Study Design
ATV, atazanavir, DRV, darunavir; FPV, fosamprenavir; LPV, lopinavir; SQV, saquinavir
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%
95% CI for Difference
12%
0.4 13.7
FavorsPI + RTV + FTC/TDF
6.7
FavorsE/C/F/TDF
0 -12%
Per
cent
age
of S
ubje
cts
(%)
94%
<1%6%
87%
1%
12%
0
10
20
30
40
50
60
70
80
90
100
Virologic SuccessW48
Virologic FailureW48
No Virologic DataW48
E/C/F/TDF (n=290) PI + RTV + FTC/TDF (n=139)
Prespecified sequential testing Statistical superiority (p = 0.025)
CD4 Cell Count (cells/mm 3) Baseline(mean)
ΔΔΔΔWeek 48(mean)
P-value(ΔΔΔΔ W48 - BL)
E/C/F/TDF 603 +40 <0.001
PI + RTV + FTC/TDF 625 +32 =0.025
STRATEGY - PI
Primary Endpoint: HIV-1 RNA < 50 c/mL
Full analysis set excluded subjects with protocol-prohibited mutations on historical genotype and those not on PI at randomization.
*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
% o
f Sub
ject
Rep
ortin
g S
ympt
oms
HIV Symptom Index
� Subjects who switched to E/C/F/TDF from PI + RTV + FTC/TDF had� 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)^
STRATEGY – PI
Patient Reported Outcomes
Diarrhea100
132222
68211
63102
5387
84223
41208
32101
3887
34100
Baseline
E/C/F/TDFPI + RTV + FTC/TDF
Week 48
E/C/F/TDF
** *
86264
48118
108283
44134
126284
56133
77260
53116
BL W48 BL W48 BL W48 BL W48
Bloating
PI + RTV + FTC/TDF
Multicenter, randomized, open-label, 96-week study
n =291
n =143• 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
NNRTI + FTC/TDF
E/C/F/TDF (Stribild®)NNRTI + FTC/TDF
Week 96Week 48
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*
STRATEGY-NNRTI
*Expanded HIV Symptom Index and HIV Treatment Satisfaction questionnairesE/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 DFStudy GS-US-236-0121 is registered with ClinicalTrials.gov, number NCT01495702.
STRATEGY - NNRTI
Study Design
EFV, efavirenz; ETR, etravirine; NNRTI, non-nucleoside reverse transcriptase inhibitors; NVP, nevirapine; RPV, rilpivirine
Single-tablet Regimen(n =338; 78%)
Atripla (n =322; 74%)
Complera (n =16; 4%)
STRATEGY - NNRTI
NNRTI and Number of Prior Regimens
95% CI for Difference
12%
-0.5 12.0
FavorsNNRTI + FTC/TDF
5.3
FavorsE/C/F/TDF
0 -12%
Per
cent
age
of S
ubje
cts
(%)
93%
1%6%
88%
<1%
11%
0
10
20
30
40
50
60
70
80
90
100
Virologic SuccessW48
Virologic FailureW48
No Virologic DataW48
E/C/F/TDF (n=290) NNRTI + FTC/TDF (n=143)
CD4 Cell Count (cells/mm 3) Baseline(mean)
ΔΔΔΔWeek 48(mean)
P-value(ΔΔΔΔ W48 - BL)
E/C/F/TDF 586 +56 <0.001
NNRTI + FTC/TDF 593 +58 <0.001
STRATEGY - NNRTI
Primary Endpoint: HIV-1 RNA < 50 c/mL
The full analysis set excluded subjects with prohibited mutations on historical genotype and those not on NNRTI at randomization.
* 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
% o
f Sub
ject
Rep
ortin
g S
ympt
oms
HIV Symptom Index
� Subjects who switched to E/C/F/TDF from EFV + FTC/TDF had� 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)^
STRATEGY – NNRTI: Efavirenz Subgroup
Patient Reported Outcomes
Vivid Dreams Insomnia Anxiety Dizziness100
136224
75212
65101
5687
119224
84209
48100
4187
103222
71208
40100
3487
90225
49211
3799
3287
BL W48 BL W48 BL W48 BL W48 BL W48 BL W48 BL W48 BL W48
****
**
BaselineE/C/FTDFNNRTI + FTC/TDF
Week 48E/C/FTDFNNRTI + FTC/TDF
Avances del tratamiento antirretroviralAvances del tratamiento antirretroviral
StudyEffect size (CI)
Medical male circumcision (MMC) (Orange Farm, Rakai, Kisumu)
57% (42, 68)
Prime-boost HIV Vaccine (Thai RV144)
31% (1, 51)
Efficacy0% 10 20 30 40 50 60 70 80 90 100%
TDF/FTC oral-PrEP in MSM (iPrEx, Grant et al 2010)
44% (15, 63)
1% tenofovir gel (Caprisa 004, Karim et al.)
39% (6, 60)
*Provisional
Immediate ART for positivePartners (HPTN052)
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
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
Avances del tratamiento antirretroviralAvances del tratamiento antirretroviral
Consenso sobre el inicio del tratamiento: Recomendaciones de GESIDA 2014
Consenso sobre el inicio del tratamiento: Recomendaciones de la DHHS
Recuento de CD4
(cél/mm 3)DHHS 2013
<350 TAR recomendado (AI)
>350 a <500 TAR recomendado (AII)
>500 TAR recomendado (BIII)
Avances del tratamiento antirretroviralAvances del tratamiento antirretroviral
Avances del tratamiento antirretroviralAvances del tratamiento antirretroviral
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.
MÉTODO
DISEÑO Encuesta transversal
MUESTRA 370 personas con VIH
PROCEDIMIENTO
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
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 antirretroviralAvances del tratamiento antirretroviral
LIMITACIONES PARA ESTOS AVANCES
61