PrEP

PROS
LA PROFILAXIS PREEXPOSICIÓN FRENTE A VIH
Roger Paredes
Unitat VIH i Institut de Recerca de la SIDA irsiCaixa
Hospital Universitari Germans Trias i Pujol
Las nuevas infecciones por VIH no han disminuido, e
incluso aumentan en grupos vulnerables
500
450
400
350
300
250
200
150
100
50
0
Figura 1.8. Evolució de la prevalença del VIH en dones treballadores
del sexe segons país d'origen. Catalunya 2005-2011
1000
2001
2003
2005
2007
UDVP
Home HTS
Dona HTS
TV
2009
2011
HSH
SIVES 2015: http://www.ceeiscat.cat/documents/sives2015.pdf
2013
30
27
24
21
18
15
12
9
6
3
0
800
600
400
200
0
Global
Taxa Home
Taxa Global
Taxa Dona
Taxa casos per 100.000 habitants
Figura 1.17. Evolució anual de la taxa de diagnòstics del VIH
segons el sexe. Registre del VIH i sida de Catalunya, 20012013
Nombre de casos de VIH
Nombre de casos de VIH
Figura 1.20. Evolució dels diagnòstics de VIH segons els
grups de transmissió. Registre de VIH i sida de Catalunya,
2001-2013
Con el preservativo no basta
Estudi ÍTACA - BCN Checkpoint
(2008-2011)
Ús del preservatiu
Sempre
714 56,3%
Gairebé
sempre
476 37,5%
A vegades
34
2,7%
Gairebé mai
15
1,2%
Mai
17
1,3%
No contesta
13
1,0%
Total
SIVES 2015: http://www.ceeiscat.cat/documents/sives2015.pdf
1,269
93,8%
Riesgo de transmisión VIH
Acute “Early” HIV patients responsible for 8-43%
of HIV transmission in serodiscordant couples
(Pinkerton, AIDS Behavior, 2008)
Source: Galvin/Cohen, 2004
6
La PrEP es eficaz
La PrEP es eficaz
Study name
Target
Drug / Dosing
Country/Region
% Protection
iPrex
(n=2499)
HSH
TDF/FTC QD vs
placebo
Peru, Ecuador, South
Africa, Brazil, Thailand,
and the United States
•
•
44% overall
92% if detectable drug
levels
TDF2
(n=1219)
HTS men &
women
TDF/FTC QD vs
placebo
Botswana
•
62%
Partners PrEP
(n=4758 couples)
Men & women,
serodiscordant
couples
TDF QD vs
TDF/FTC QD vs
placebo
Kenya and Uganda
•
•
67% TDF
75% TDF/FTC (90% if
detectable drug levels)
Bangkok
Tenofovir Study
(n=2413)
IVDU
TDF
Thailand
•
•
49% overall
74% if detectable drug
levels
FEM-PrEP
(n=2120)
HTS women
TDF/FTC QD
South Africa, Kenya,
and Tanzania
•
•
•
No reduction
<50% with drug levels
Early stop: low power
VOICE
(n=5029)
HTS women
TDF/FTC QD vs
topical vaginal
TDF vs oral &
topical placebos
Southern Africa
•
•
No reduction
<30% with drug levels
* In all cases, PrEP provided alongside condoms, individualised risk reduction, adherence counselling, etc
8
La PrEP es eficaz (si se toma…)
www.prepwatch.org
9
PrEP “on demand” funciona
N=414, randomized 1:1
13 months follow-up
16 new HIV transmission:
•2 in active arm (incidence 0.94 per 100 PY)
•14 in placebo group (incidence 6.6 per 100 PY)
86% reduction in the incidence of HIV T
NNT for one year to prevent an infection = 18
U S Pu
b lic H
ealth
Población diana (CDC 2014)
Servic
e
P R EE
X P OS
U RE
F OR
PRO P
T HE
PR
H YL
I NF E
AX
CT I O E V E N T I O
N IN
N O F IS
STAT
T HE
ES - 2
U NI T HI V
0 14
A CL
ED
INIC
AL
PR AC
T ICE
G UID
E LIN
E
BB
ox
efining
ox3.3.DD
efining“substantial
“substantialrisk”
risk”
Substantial risk of HIV infection is provisionally defined as HIV incidence greater than 3 per 100
Substantial risk of HIV infection is provisionally defined as HIV incidence greater than 3 per 100
person–years in the absence of PrEP. HIV incidence greater than 3 per 100 person–years has
person–years in the absence of PrEP. HIV incidence greater than 3 per 100 person–years has
been identified among some groups of men who have sex with men, transgender women in
been identified among some groups of men who have sex with men, transgender women in
many settings and heterosexual men and women who have sexual partners with undiagnosed
many settings and heterosexual men and women who have sexual partners with undiagnosed
or untreated HIV infection. Individual risk varies within groups at substantial risk depending on
or untreated HIV infection. Individual risk varies within groups at substantial risk depending on
individual behaviour and the characteristics of sexual partners. Most of the PrEPtrials reviewed
individual behaviour and the characteristics of sexual partners. Most of the PrEPtrials reviewed
for this recommendation identified and recruited groups at substantial risk of acquiring HIV
for this recommendation identified and recruited groups at substantial risk of acquiring HIV
infection, as demonstrated by the HIV incidence rate among participants in control arms that
infection, as demonstrated by the HIV incidence rate among participants in control arms that
ranged between 3 to 9 per 100 person-years in most studies. Indeed, the HIV incidence in
ranged between 3 to 9 per 100 person-years in most studies. Indeed, the HIV incidence in
control arms of PrEPtrials was often higher than anticipated, suggesting that PrEPattracts
control arms of PrEPtrials was often higher than anticipated, suggesting that PrEPattracts
people at particularly high risk (187). In locations where the overall incidence of HIV infection is
people at particularly high risk (187). In locations where the overall incidence of HIV infection is
low, there may be individuals at substantial risk who would be attracted to PrEPservices.
low, there may be individuals at substantial risk who would be attracted to PrEPservices.
HIV incidence greater than 2 per 100 person–years was considered sufficient to warrant
HIV incidence greater than 2 per 100 person–years was considered sufficient to warrant
offering oral PrEPin the recommendations issued by the International Antiviral Society – USA
offering oral PrEPin the recommendations issued by the International Antiviral Society – USA
expert panel in 2014 (191). Thresholds for offering PrEPmay vary depending on a variety of
expert panel in 2014 (191). Thresholds for offering PrEPmay vary depending on a variety of
considerations, including available resources and the relative costs, feasibility and demand for
considerations, including available resources and the relative costs, feasibility and demand for
PrEPand other opportunities.
PrEPand other opportunities.
12
La PrEP tiene una toxicidad leve /
moderada y reversible
Study name
Target
Drug / Dosing
Toxicity
iPrex
(n=2499)
HSH
TDF/FTC QD vs placebo
Nausea 9% vs 5%
US-MSM Safety
(n=400)
HSH
TDF vs Placebo
Back pain
BMD 1%
TDF2
(n=1219)
HTS men & women
TDF/FTC QD vs placebo
Nausea, vomiting, dizziness
(1st month)
Bangkok Tenofovir
Study
(n=2413)
IVDU
TDF
Nausea, vomiting (1st 2
months)
Ipergay ANRS
(n=414)
HSH
On-demand TDF/FTC
Nausea, vomiting (1st 2
months)
13
Ningún estudio ha demostrado
incremento en toxicidad grado 3 o 4
Table 5: Evidence Summary— Safety and Toxicity
Outcome Analyses
Study
Agent
Control
Grade 3/4 Adverse Clinical Eventsa
iPrEx
TDF2
West African Trial
52 events
9 events
NR
59 events
10 events
NR
Grade 3/4 Adverse Laboratory Events a
iPrEx
TDF2
West African Trial
59 events
32 events
1 event
48 events
32 events
5 events
Grade 3/4 Adverse Events (Clinical and Laboratory)a
Partners PrEP
TDF: 323 events
TDF/FTC: 337 events
FEM-PrEP
NR
US MSM Safety Trial
36 events
VOICE
NR
BTS
175 events
NR, not reported.
307 events
NR
26 events
NR
173 events
14
Las resistencias no justifican no
realizar PrEP
Table 6: Evidence Summary— HI V Resistance Findings (TDF or FTC Drug Resistant Virus Detected)
Outcome Analyses
Study
iPrEx
US MSM Safety Trial
Partners PrEP
TDF2
FEM-PrEP
West African Trial
VOICE
BTS
NR, not reported.
Agent
2 resistant viruses among 2 persons infected at baseline
0 resistant viruses among 36 persons infected after baseline
0 resistant viruses among 3 persons infected after baseline (in delayed
arm before starting drug)
2 resistant viruses among 5 persons infected at baseline and randomly
assigned to TDF
1 resistant virus among 3 persons infected at baseline and randomly
assigned to TDF/FTC
0 resistant viruses among 27 persons infected after baseline
1 resistant virus in 1 person infected at baseline
0 resistant viruses among 9 persons infected after baseline
Control
1 resistant virus among 8 persons infected at baseline
0 resistant viruses among 64 persons infected after baseline
1 resistant virus among 1 person infected at baseline
0 resistant viruses among 3 persons infected after baseline
0 resistant viruses among 6 persons infected at baseline
0 resistant viruses among 51 persons infected after baseline
1 resistant virus in 1 person infected at baseline (very low
frequency and transient detection)
0 resistant viruses among 24 persons infected after baseline
4 resistant viruses among 33 persons infected after baseline
1 resistant virus in 35 persons infected after baseline
0 resistant viruses among 2 persons infected while on TDF
NR
NR
—
0 resistant viruses among 49 persons infected after baseline
Las resistencias no justifican no
realizar PrEP
• La mayoría de infecciones a pesar de la PrEP son por virus
susceptibles a los fármacos o tratables
• Mayoría de casos, M184V/I a FTC (o 3TC) hipersusceptibilidad a TDF y ABC
• Raramente K65R a TDF (potencialmente más problemático en África)
• A menudo se trata de infecciones en fase hiperaguda no
diagnosticadas
• Se puede prevenir con tests de 4ª generación (ventana 4-10 días) y incluso CV
Coste-efectividad
• El coste es la limitación real
• A precio actual y administración continuada
Los costes de la PrEP son sustanciales
• Es coste-efectiva en poblaciones de alto
riesgo. Tasas incidencia
•
• 2-3/100.000 PY <100.000 US$/QALY
• 0.8/100.000 PY >200.000 US$/QALY
•
Muy sensible a coste o efectividad
• Llega TDF genérico 2017
• PrEP “on demand” menor coste
• Es posible simplificar el seguimientoJA
James Carville – Clinton 1992 Campaign aganst Bush Sr.
Dr Vall
Yo
Counseling i
Test del VIH
Control de las ITS
Condones
Microbicidas
Prevención
integral
Vacunas
Anillos
vaginales
Circumcisión
masculina
Profilaxis basada en
ARV
TasP
PEP
PrEP
La PrEP ya está
en la calle… y
en Tinder® !
Encuesta ACCEPT >600 HSH VIH•22%
HSH VIH- conocían la PrEP,
sobretodo mediante internet
•60% aceptación, 25% NS/NC
•75% la tomarían como inyección
mensual o toma única pre-sexo
•46% si causara efectos adversos
•Sólo un 12% si costara 400€
•19% no utilizaría preservativo ante
PrEP
SIVES 2015: http://www.ceeiscat.cat/documents/sives2015.pdf
19
Conclusiones
• En VIH, tratar es prevenir
• La PrEP funciona
• La PrEP a demanda funciona
• La toxicidad o resistencias no justifican no hacerla
• La limitación real es el coste y la implementación
• Y las ideas preconcebidas, incluídas las de índole moral /
religiosa ¿por qué tengo que pagar yo para que “ellos”
tengan relaciones sexuales?
• La PrEP no evita embarazos ni otras ITS Con PrEP no
basta
• No existe evidencia sólida de compensación de riesgo
• Vamos por detrás de muchos otros países