Pre-Exposure Prophylaxis: The Missing
Piece of Combination Prevention
Fabio Mesquita, MD, PhD
Director
Department of STI, AIDS and Viral Hepatitis
MoH - Brazil
Use of PrEP for other conditions
• Antimalarial prophylaxis
• Isoniazid prophylaxis for TB
• Opportunistic infections prophylaxis in AIDS
– Co-trimoxazol for Pneumocystis jirovecii
– Azitromycin for Mycobacterium avium
• Contraceptive pill
Use of ART to prevent HIV transmission
ACTG 076 Study Group
Use of ART to prevent HIV transmission
67.5% reduction in MTCT
The beginning…
• First studies with PrEP in the early 2000s
• Some studies interrupted:
– Cambodia, Cameroon, Nigeria
• New studies after 2005
• First promising results
The beginning…
Effectiveness of Studies
PROUD (TDF/FTC)
ipergay (TDF/FTC)
West African Trial (TDF)
Bangkok tenofovir study (Women)
Bangkok tenofovir study (Men)
Bangkok tenofovir study (TDF Detectable)
Bangkok tenofovir study (IDU General)
MTN003/VOICE (TDF)
MTN003/VOICE (TDF/FTC)
MTN003/VOICE (TDF Gel)
CAPRISA 004 (TDF Gel)
iPrEX (TDF/FTC Detectable)
iPrEX (Adh. >90%)
iPrEX (Adherence >50%)
iPrEX (MSM - General)
FEMPrEP
TDF2 (TDF Detectable)
TDF2 (Women)
TDF2 (Men)
TDF2 (TDF/FTC General)
Partners PrEP (TDF Detectable)
Partners PrEP (TDF/FTC Detectable)
Partners PrEP (TDF/FTC Men)
Partners PrEP (TDF Men)
Partners PrEP (TDF/FTC Women)
Partners PrEP (TDF Women)
Partners PrEP (TDF general)
Partners PrEP (TDF/FTC General)
86,0%
86,0%
65,0%
79,0%
37,6%
73,5%
48,9%
-49,0%
-60,0%
-4,0%
15,0%
39,0%
92,0%
73,0%
50,0%
44,0%
6,0%
85,0%
49,0%
80,0%
63,0%
86,0%
90,0%
84,0%
63,0%
66,0%
71,0%
67,0%
75,0%
-40,0%
-20,0%
0,0%
20,0%
40,0%
60,0%
80,0%
100,0%
McCormack S (2015), Molina JM (2015), Baeten JM (2015), Murnane PM (2013), Baeten JM (2012), Donnell D (2014), Thigpen MC (2012), Damme LV (2012), Grant RB (2010), Anderson PL
(2012), Karim A (2004), Marrazzo JM (2015), Choopanya K (2013), Peterson L (2006)
VOICE
Bangkok Tenofovir Study Group
Effectiveness: 48.9%
Partners PrEP Study Team
4747 HIV-1 serodiscordant couples
(Kenya and Uganda)
TDF x TDF/FTC x Placebo
Partners PrEP Study Team
Kaplan–Meier Estimates of the Primary End Point in the Modified Intention-to-Treat Analysis,
According to Study Treatment.
Effectiveness:
TDF: 67%
TDF/FTC: 75%
Baeten JM et al. N Engl J Med 2012;367:399-410
iPrEx
iPrEX Study Team
2499 MSM
(Peru, Ecuador, South Africa, Brazil, Thailand, United States)
TDF/FTC x Placebo
iPrEX Study Team
Kaplan–Meier Estimates of Time to HIV Infection (Modified Intention-to-Treat Population).
Effectiveness: 44%
Grant RM et al. N Engl J Med 2010;363:2587-2599
Effectiveness and Adherence
Baeten JM (2015), Murnane PM (2013), Baeten JM (2012), Donnell D (2014), Thigpen MC (2012), Damme LV (2012), Grant RB (2010), Anderson PL (2012), Marrazzo JM (2015), Choopanya K (2013),
Ipergay Trial
Ipergay Trial
Ipergay Trial
Ipergay Trial
Ipergay Trial – no evidence of risk compensation
Ipergay Trial
• No evidence of Risk Compensation:
– reporting non-condom receptive anal intercourse decreased from 34% to 25%
among PrEP group
– reporting non-condom receptive anal intercourse decreased from 27% to 20%
among control group
– Syphilis incidence was similar among PrEP recipients and non-recipients
(7·2 infections per100 patient-years vs 5·4 infections per 100 patient-years, HR 1·35, 95 CI 0·83–2·19).
PROUD Study
PROUD Study
PROUD Study
PROUD Study
Ongoing and Planned PrEP studies
Study
Partners Demonstration Project
AMPrEP (Amsterdam PrEP
PRELUDE Study
PrEPBrasil
CHAMPS
Sibanya Health Project
VicPrep Demonstration Project
SAPPH-Ire
MP3-Youth
Benin Demonstration Project
Senegal Demonstration Project
TAPS Demonstration Project
IPCP-Kenya
Nigerian National Agency for the Control of AIDS
Durbar (DMSC)
Be PrEPared - Antwerp PrEP Project
NZ PrEP
Health4Men initiative
Bangkok Tenofovir Study Follow-up
The Demo Project
East Bay Consortium/CRUSH
LAC PATH PrEP
ALERT
SHIPP
SPARK Project
Project PrEPare
HPTN 073
iPrex OLE
CDC494 (TDF2 follow-up)
PROUD
IPERGAY
HPTN067 (ADAPT)
HPTN 069 (NEXT-PrEP)
HPTN 082 (Vanguard Study)
HPTN 077
HPTN 076
HPTN 083
Location
Kenya, Uganda
Netherlands
Australia
Brazil
South Africa
South Africa
Australia
Zimbabwe
Kenya
Benin
Senegal
South Africa
Kenya
Nigeria
India
Belgium
New Zealand
South Africa
Thailand
US
US
US
US
US
US
US
US
Brazil, Peru, Ecuador, South Africa,
Thailand, US
Botswana
UK
Canada, France
South Africa, Thailand, US
US
Population
Serodiscordant couples
MSM, Transgender
Men and Womem at high risk
MSM, Transgender
Heterosexual Adolescents
MSM
MSM, Transgender, serodiscordant
FSW
Adolescents
FSW
FSW
FSW
FSW, MSM, Young Womem
Serodiscordant couples
Female and Transgender SW
MSM
People at high risk
MSM
PWID
MSM, Trangender Women
Young MSM of color
MSM
MSM
MSM and Womem
MSM and Transgender Womem
Adolescents MSM (15-22)
MSM
South Africa, Zimbabwe, US
TMC278 LA - Women
MSM, Transgender Women
Heterosexual Men and Women
MSM
MSM
Womem, MSM and trangender
MSM and Womem
Young African Women
GSK1265744 - Men and Women
Cabotegravir - MSM and Transgender
Women
Completion
2016
2018
2016
2016
2016
2016
2018
2015
2016
2017
2017
2017
2016
2016
2017
2015
2017
2017
2015
2017
2017
2016
2015
2015
2016
2016
2015
2015
PrEP uptake and associated factors
among MSM and TGW in the PrEP Brazil
demonstration project
Brenda Hoagland, Valdilea G. Veloso, Raquel B. De Boni, José Valdez Madruga, Esper G.
Kallas, Nilo Martinez Fernandes, Ronaldo I. Moreira, Albert Y. Liu and Beatriz Grinsztejn
for the PrEP Brazil Study Team
IAS 2015- Vancouver
My personnal position
WHO and UNAIDS Positions
Where are we?
US
A
THAILA
ND
MALAYSIA
ARV Costs
ARV Costs
Questions to be adressed
•
•
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•
•
•
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Dosing (7 days, 4 days or event driven 4 pills)
Target population
When to stop
TDF x TDF/FTC
Costs
Public x Private
Ongoing Studies
Conclusion
• High efficacy for many key populations
• Adherence is a major issue
• No evidence of risk compensation
• No evidence of ARV resistance
Comprehensive HIV Prevention
Acknowledgments
•
•
•
•
•
•
Leandro Sereno (WHO Brazilian CO)
Beatriz Grinsztejn (FIOCRUZ)
Valdiléa G. Veloso (FIOCRUZ)
Jean-Michel Molina (ANRS France)
Marcelo Freitas (Brazilian MoH)
Chris Beyrer (IAS)
Thank you
Obrigado
[email protected]