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.

1. X

2. Avances del tratamiento aannttiirrrreettrroovviirraall

3. Avances del tratamiento aannttiirrrreettrroovviirraall

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. 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. 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. 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. 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. La coformulación de Darunavir pronto será
posible

10. Avances del tratamiento aannttiirrrreettrroovviirraall

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. 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. 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. Avances del tratamiento aannttiirrrreettrroovviirraall

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. 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. 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. 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. 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. Avances del tratamiento aannttiirrrreettrroovviirraall

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. 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. 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. 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. 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. Avances del tratamiento aannttiirrrreettrroovviirraall

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. 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. 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. 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. 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. 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. 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. Avances del tratamiento aannttiirrrreettrroovviirraall

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. 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. 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. 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. 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. 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. 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. 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. Avances del tratamiento aannttiirrrreettrroovviirraall

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. 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. Avances del tratamiento aannttiirrrreettrroovviirraall

47. Consenso sobre el inicio del tratamiento:
Recomendaciones de GESIDA 2014

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. Avances del tratamiento aannttiirrrreettrroovviirraall

52. Avances del tratamiento aannttiirrrreettrroovviirraall

53. 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.

54. 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

55. DATOS SANITARIOS
MEDIANA 12
AÑOS

56. IMPORTANCIA CARACTERISTICAS TRATAMIENTO
PARA ADHERENCIA

57. IMPORTANCIA CARACTERISTICAS TRATAMIENTO
PARA ADHERENCIA

58. IMPORTANCIA CARACTERISTICAS TRATAMIENTO
PARA ADHERENCIA

59. IMPORTANCIA CARACTERISTICAS TRATAMIENTO
PARA ADHERENCIA (FACTORES)

60. Avances del tratamiento aannttiirrrreettrroovviirraall

61. LIMITACIONES PARA ESTOS AVANCES
61