Oral pre-exposure prophylaxis (PrEP) for populations
at substantial HIV risk
Dr. Rachel Baggaley, HIV dept. WHO, Geneva
GNP+ WEBINAR: What does PrEP mean for
people living with HIV: science, policy
and implementation?
Date: Thursday, 30th July 2015
Time: 4pm CET
Why consider PrEP
2.1 million people infected with HIV in 2013
Among key populations:
 Burden of HIV infection is 19 fold higher among MSM and 49 fold
higher among transgender women compared with the general
population.
 High rates of HIV incidence among MSM across all regions.
 High HIV prevalence among sex workers in Africa >20% in
Nigeria;>50% in South Africa and Zimbabwe.
 Estimates from South Africa show a 5.6% HIV prevalence among girls
aged 15–19 years, increasing to 17.4% for young women aged 20–
24 years.
Demonstrated need for more prevention options
HIV incidence in 18-35 year
women in this community:
9.1%
9.1 per 100 women-yrs
(95% CI: 7 - 12)
Source: Abdool Karim Q et al, Science 2010
HIV in pregnant women in
rural
South Africa (2001-2013)
Age Group
(Years)
HIV Prevalence
(N=4818)
≤16
11.5%
17-18
21.3%
19-20
30.4%
21-22
39.4%
23-24
49.5%
>25
51.9%
Source: Abdool Karim Q, Int J Epi, 2014
“Explosive HIV epidemic”
among MSM in Bangkok
Rationale to focus initial PrEP
efforts on younger MSM
60-month cumulative HIV-incidence among MSM in Bangkok, 2006–2012.
MSM=men who have sex with men
Source: van Griensven F, et al. AIDS, 2013 Mar 13;27(5):825-32.
Study
Overall evidence for PrEP: July 2015
Effect size (CI)
IPERGAY – on demand Truvada
86% (39; 99)
(MSM – France & Canada)
PROUD – daily oral Truvada
86% (62; 96)
(MSM – United Kingdom)
Partners PrEP – daily Truvada
75% (55; 87)
(Discordant couples – Kenya, Uganda)
Partners PrEP – daily oral Tenofovir
67% (44; 81)
Oral PrEP
(Discordant couples – Kenya, Uganda)
TDF2 – daily Truvada
62% (22; 84)
(Heterosexuals men and women- Botswana)
iPrEx – daily Truvada
44% (15; 63)
(MSM - America’s, Thailand, South Africa)
FEMPrEP – daily Truvada
6% (-52; 41)
(Women – Kenya, South Africa, Tanzania)
MTN003/VOICE – daily Truvada
-4% (-49; 27)
(Women – South Africa, Uganda, Zimbabwe)
MTN003/VOICE – daily Viread
-49% (-129; 3)
Topical PrEP
(Women - South Africa, Uganda, Zimbabwe)
CAPRISA 004 – coital Tenofovir gel
39% (6; 60)
(Women – South Africa)
MTN003/VOICE – daily Tenofovir gel
15% (-21; 40)
(Women – South Africa, Uganda, Zimbabwe)
FACTS 001– coital Tenofovir gel
0% (-40, 30)
(Women – South Africa)
-130
-60
-40
-20
0
20
40
Effectiveness (%)
60
80
100
Adherence and effectiveness
GRADE table: HIV infection
Quality assessment
No of
studies
Design
Risk of bias
Inconsistency Indirectness Imprecision
No of patients
Oral PrEP
Other
(containing
considerations
tenofovir)
Control
Effect
Relative
(95% CI)
Quality
Importance
Absolute
HIV Infection--PrEP vs. Placebo--Adherence >70%
3
randomised
trials
no serious
risk of bias
39/3866
(1%)
79/2284
(3.5%)
RR 0.30
(0.21 to
0.45)
24 fewer per 
1000 (from 19 HIGH
fewer to 27
fewer)
CRITICAL
53/2455
(2.2%)
97/2457
(3.9%)
RR 0.55
(0.39 to
0.76)
18 fewer per
1000 (from 9
fewer to 24
fewer)

HIGH
CRITICAL
no serious
no serious no serious none
inconsistency indirectness imprecision
146/3002
(4.9%)
95/2031
(4.7%)
RR 0.95
(0.74 to
1.23)
2 fewer per 
1000 (from 12 HIGH
fewer to 11
more)
CRITICAL
no serious
no serious no serious none
inconsistency indirectness imprecision
3/367
(0.82%)
22/353
(6.2%)
RR 0.15
(0.05 to
0.46)
53 fewer per 
1000 (from 34 HIGH
fewer to 59
fewer)
CRITICAL
no serious
no serious no serious none
inconsistency indirectness imprecision
HIV Infection--PrEP vs. Placebo--Adherence 40-70%
2
randomised
trials
no serious
risk of bias
no serious
no serious no serious none
inconsistency indirectness imprecision
HIV Infection--PrEP vs. Placebo--Adherence <40%
2
randomised
trials
no serious
risk of bias
HIV infection--PrEP vs. no PrEP
2
randomised
trials
no serious
risk of bias
Systematic review results
Analysis
No. of
studies
RCTs comparing PrEP to placebo
Overall
10
Adherence
High (>70%)
3
Moderate (41-70%)
2
Low (≤40%)
2
Mode of Acquisition
Rectal
4
Vaginal/penile
6
Biological sex1
Male
7
Female
6
2
Age
18 to 24 years
3
≥25 years
3
Drug Regimen
TDF
5
FTC/TDF
7
Drug Dosing
Daily
8
Intermittent
1
RCTs comparing PrEP to no PrEP
Overall
2
1
Sample Size
(N)
Risk Ratio
(95% CI)
p-value
17424
0.49 (0.33-0.73)
0.001
70.9
--
6150
4912
5033
0.30 (0.21-0.45)
0.55 (0.39-0.76)
0.95 (0.74-1.23)
<0.0001
<0.0001
0.70
0.0
0.0
0.0
<0.0001
0.009
ref
3167
14252
0.34 (0.15-0.80)
0.54 (0.32-0.90)
0.01
0.02
29.1
80.1
0.36
8706
8716
0.38 (0.25-0.60)
0.57 (0.34-0.94)
<0.0001
0.03
34.5
68.3
0.19
2997
5129
0.71 (0.47-1.06)
0.45 (0.22-0.91)
0.09
0.03
20.5
72.4
4303 active
5693 active
0.49 (0.28-0.86)
0.51 (0.31-0.83)
0.001
0.007
63.9
77.2
0.88
17024
400
0.54 (0.36-0.81)
0.14 (0.03-0.63)
0.003
0.01
73.6
0.0
0.14
720
0.15 (0.05-0.46)
0.001
0.0
NA
I2
P-value (metaregression)
The iPrEx trial included 313 (13%) transgender women. 2 Includes only studies that stratified age by
<25 and ≥25.
0.29
WHO guidance on PrEP (2012,
2014, 2015, 2016)
2012. Guidance for MSM & Serodiscordant Couples in the context of
demonstration projects to encourage countries to conduct such
demonstration projects
201. Consolidated KP Guidelines
Recommendation for MSM
Among men who have sex with men, PrEP is recommended as an additional HIV
prevention choice within a comprehensive HIV prevention package (strong
recommendation, high quality of evidence).
2015
Oral PrEP (containing TDF) should be offered as an additional prevention
choice for people at substantial risk of HIV infection as part of combination
prevention approaches forthcoming
2016
Implementation guidance, package of implementation tools for a variety of
implementers and populations forthcoming
Implementation tool / guidance, forthcoming
Forthcoming new WHO PrEP recommendation
New PrEP recommendation in 2015 interim ARV GL forthcoming
Oral PrEP (containing TDF) should be offered as an additional prevention choice for people
at substantial risk of HIV infection as part of combination prevention approaches
• Enabling recommendation
• Not population specific
– For people at substantial HIV risk (provisionally defined as HIV incidence > 3 per 100 person–years in the
absence of PrEP)
• Offer as an additional prevention choice
• Provide PrEP within combination prevention
–
–
–
Condoms and lube
Harm reduction
HIV testing and links to ART
• Provide PrEP with comprehensive support
–
–
–
–
Adherence counselling
Legal and social support
Mental health and emotional support
Contraception and reproductive health services
Who might benefit from PrEP –
people at 'substantial' HIV risk
Step 1. consider an incidence in a community/population of ≈ 3 per 100 person–years
Step 2. Within a population with incidence ≈ 3% there will be significant heterogeneity.
Not all people will have high HIV risk. Simple screening questions will help identify those at
most risk within this population or community and those who are not using other effective
HIV prevention methods
Step 3 .Those who are identified at highest HIV risk and a would welcome and want to take
an additional prevention option
'offering PrEP' could be considered.
Defining ‘substantial risk’
• PrEP trials recruited populations at substantial risk of
acquiring HIV infection, as defined by HIV incidence
of >2 / 100 PY in control arms.
• HIV incidence >2.0 per 100 person years was deemed
sufficient to warrant offering oral PrEP in the
recommendations by IAS-USA expert panel in 20141.
• Modeling suggests that incidence >2-3/100 PY would
be cost effective
1Marrazzo
JM, del Rio C, Holtgrave DR, et al. HIV prevention in clinical care settings: 2014 recommendations
of the International Antiviral Society– USA Panel. JAMA 2014; 312:390–409.
Defining ‘substantial risk’
HIV incidence in control arms of PrEP studies
Study
Population
BKK TDF
IDU
FEM PREP Women
VOICE
Women
iPrEx RCT MSM and
TGW
iPrEx Gap MSM and
TGW
iPrEx OLE MSM and
TGW
Partners
Men and
PrEP RCT
women
in SDC
TDF2
Men and
Women
PROUD
MSM
Ipergay
MSM
Incident HIV
Infections
Person Years
HIV Incidence
Rate
95% CI
33
35
60
83
4823
n/a
1308
2113
0.7
5.0
4.6
3.9
0.47 to 0.96
n/a
3.5 to 5.9
3.1 to 4.8
43
1044
4.1
3.1 to 5.6
13
n/a
2.1
1.5 to 4.5
52
1578
2.0
n/a
24
n/a
3.1
n/a
19
14
214
n/a
8.9
6.6
6.0 to 12.7
n/a
Van Damme NEJM 2012; Baeten NEJM 2012; Marrazzo NEJM 2015; Thigpen NEJM 2012; Choopanya
Lancet 2013; Grant CROI 2013; Grant Lancet Infectious Diseases 2014.
Where we are now ?from trials to implementation
• Who will be offered PrEP?
– What subgroups of population/s at 'substantial HIV risk' would benefit most
– How to identify/screen for/target
– Who in those groups would find acceptable/ most likely to use
• PrEP delivery approaches and issues?
– Where best to deliver PrEP
• STI, FP, ANC/PNC, HIV, community…
– Monitoring issues
• Frequency of visits/follow up
• Frequency of HIV re-testing for those on PrEP
• How much screening for safety
• How to deliver PrEP effectively?
– How to support adherence to daily PrEP use
– What does adherence to PrEP "mean" – how good is good enough
– How to monitor adherence to PrEP? (differs from treatment)
Implementation guidance
• Identifying people at substantial risk – modelling and costing
• Testing – options and in line with national testing algorithms, ?role of self-
testing
– Prior to offer
– During taking
• Pre-screening and monitoring
– Renal – systematic review
– (bone) – systematic review
– Hepatitis B – systematic review
• Drug resistance – systematic review
• Issues for different populations
–
–
–
–
–
MSM
Transgender
PWID
Sex workers
AGYW – esp. adolescent specific issues
Immediate issues to address
•
•
•
Making the case for PrEP, but not overselling it
– Cost and cost-effectiveness
– How does cost compare to other prevention options
Defining and identifying the populations
– Initial focus of the very high incidence populations
– Screening tools for assessing risk
Policy
– How to support PrEP availability in countries
– How to involve communities where PrEP programmes are planned to inform and
empower them to choose
– How to address legal issues and constraints
• Social issues and human rights
– Always within a comprehensive prevention programme
– Always voluntary and informed
Listening to and learning from communities
“Young people need more
than just PrEP tablets. They
need social support to foster
their self-esteem and
motivation.”
Ivan Fahy
ShOUT! LGBT Youth Group
(Ireland)
"PrEP empowers me"
Bathabile, 23
Zimbabwean
sex worker on PrEP
“If we continue to see sexual health as taboo,
more unnecessary infections will occur.”
Mark Josef Rapa
University of Malta LGBT Society