1. Can we prevent infection after an exposure
Can we prevent infection after an exposure? The world of post-exposure prophylaxis (PEP)
James Wilton
Project Coordinator
Biomedical Science of HIV Prevention 1

2. HIV/AIDS in Canada Number of people living with HIV2
Number of people living with HIV
57,000 in 2005
65,000 in 2008
2,200 to 4,200 infected in 2005
2,300 to 4,300 infected in 2008
MSM (44%)
People who use injection drugs (17%)
Women (26%)
Aboriginal (12.5%)
Source: Public Health Agency of Canada 2 2

3. Improving HIV prevention3
Improving HIV prevention
Do better with the strategies that we already have
Develop new biomedical technologies to prevent HIV
Adopt a more comprehensive approach to HIV/AIDS prevention

4. What is post-exposure prophylaxis (PEP)?
 After
Exposure
 When a fluid containing HIV comes into contact with mucous membranes or non-intact skin
Prophylaxis
 An action taken to prevent infection or disease

5. What is PEP to prevent HIV infection?
The use of a combination of antiretrovirals by HIV-negative individuals for a short period of time after a suspected or known exposure to HIV
Must be started as soon as possible but within hours after the exposure
Must be taken everyday for 28 days
Must avoid additional exposures while taking PEP
Types of exposures
Occupational
Non-occupational 5 5 5 5

6. Occupational vs. non-occupational exposures
Work-related exposures to HIV
Needle-stick injuries
Sharp objects
“Standard of care”
Non-occupational (nPEP)
Exposures outside of the workplace
Non-consensual sex
Consensual sex
Needle sharing
Not “standard of care”

7. Does PEP work? No randomized controlled studies Observational studies
Studies with control groups
Evaluations of PEP programs
Indirect evidence
Non-human primate (monkey) studies
Prevention of mother-to-child transmission

8. How does PEP work?
Infection does not occur instantly after an exposure to HIV
The virus needs to spread throughout the body
This may take up to 3 days after the exposure
The “window of opportunity” for PEP
The brief period of time - after an exposure - where infection has not yet occurred
During this time, PEP may be able to stop HIV from causing an infection 8 8 8 8 8

9. How well does PEP work? We don’t know how protective PEP is
We know it is not 100% protective
People have become infected despite using PEP
Protection likely depends on:
Starting PEP quickly
Being adherent
The risk of transmission from the exposure
Avoiding additional exposures
The number and type of antiretrovirals used 9 9 9

10. Does occupational PEP work?
Study details
712 healthcare workers exposed to HIV-infected blood
Study findings
256 did use PEP
9 became infected
456 did not use PEP
24 became infected
PEP reduced the risk of HIV transmission by 81%

11. Does non-occupational PEP work?
Study details
200 gay men in Brazil given a 4-day starter-pack of PEP
Followed for over 2 years
Study findings
68 men did use PEP after a high risk exposure
1 became infected
86 men did not use PEP after a high risk exposure
10 became infected
Study did not calculate effectiveness of nPEP

12. Failure of nPEP to prevent infection is rare
# People who used nPEP
# HIV infections
Amsterdam
261 5
France
776 1
Denmark
374
Australia
1552
Switzerland
710
San Francisco
702 6
Montreal
~900
It is difficult to interpret how protective PEP is…
Would people have remained uninfected without using PEP?
Among those who became infected, was PEP used correctly? 12 12

13. What’s involved in taking PEP?
Assessment
Counseling
Prescription
Follow-up

14. What’s involved in taking PEP?
Assessment
Was the exposure within the last 72 hours?
Is the exposed person HIV-negative?
Was the exposure high-risk?
What activity led to the exposure?
What was the HIV status of the source person?
Counseling
Prescription
Follow-up 14 14

15. Guidelines for non-occupational PEP
When is PEP recommended?
Example, the CDC nPEP guidelines
Is there a substantial risk from the activity?
No  PEP not recommended
If yes, was the exposure to someone who was HIV-positive?
Unknown  Case-by-case basis
Yes  PEP recommended

16. What’s involved in taking PEP?
Assessment
Counseling
What are the risks and benefits of starting PEP?
Is the exposed person ready to start PEP?
Adherence and risk-reduction counseling
Prescription
Follow-up 16 16

17. What’s involved in taking PEP?
Assessment
Counseling
Prescription
What antiretrovirals? How many?
Starter-packs
Follow-up 17 17

18. Guidelines for non-occupational PEP
USA
Australia
WHO UK
Europe
Timing of PEP
Within 72 hours
Within 48 hours
Number of antiretrovirals
2 or 3 3
What antiretrovirals?
Two NRTIs
Two NRTIs + PI/NNRTI
Two NRTIs + tenofovir
Two NRTIs + PI
Truvada + Kaletra
Duration
28 days
Barber and Benn 2010
NRTI = nucleoside reverse transcriptase inhibitor
NNRTI = non-nucleoside reverse transcriptase inhibitor
PI = protease inhibitor
Truvada = tenofovir + emtricitabine
Kaletra = Lopinavir 18 18

19. What’s involved in taking PEP?
Assessment
Counseling
Prescription
Follow-up
Ongoing risk-reduction and adherence counseling
Monitoring/management of side-effects and toxicity
HIV testing 19 19

20. Why do so few people use nPEP in Canada?
People may not think they are at risk
Lack of national and provincial guidelines
Use of nPEP is not promoted
Only available in some emergency departments and urgent care clinics
Cost is only covered by some provincial and private insurance plans
Side-effects, adherence, monitoring, counseling 20 20 20 20

21. Why is there reluctance to make nPEP more widely available?
Feasibility
Cost-effectiveness
Risk compensation

22. Why is there reluctance to make nPEP more widely available?
Feasibility
Research suggests that nPEP programs are feasible but challenges exists
Cost-effectiveness
Research suggests that targeted nPEP programs are cost-effective
Risk compensation
Research shows that there is little evidence of risk compensation 22 22

23. Enhancing the potential benefit of PEP
Access to PEP provides an opportunity to offer additional services to people at high risk of infection
Research study
Study details
In addition to PEP, participants received either:
Standard risk-reduction counseling (2-sessions)
Enhanced risk-reduction counseling (5-sessions)
Participants followed for a year after initiating PEP
Study findings
Standard counseling  12.3% became infected
Enhanced counseling  2.4% became infected
Combining PEP with enhanced risk-reduction counseling can make it a more effective prevention tool

24. A comprehensive approach to PEP
Integration into a comprehensive prevention program
Targeted outreach and educational campaigns
Prevention, care and support services
Adherence counseling and support
Risk-reduction counseling
Psychological counseling and trauma support
Mental health and addiction services
Advocacy to improve access

25. Clinique l’Actuel: 9 years experience with nPEP
Sexual health clinic in Montreal, Quebec
Over 1,139 consultations
Prescribed to over 900 people
Majority of PEP users are gay men
80% first time using PEP
Average time to consultation after exposure - 29 hours
Challenges
68% complained of side-effects
50% completed follow-up
6 HIV infections
Many reported ongoing exposures

27. CATIE’s Programming Connection

28. CATIE Resources: PEP factsheet and article

29. I also wanted to draw your attention to an excellent position paper created by the Health Initiative for Men – a gay men’s sexual health organisation in BC.
The position paper reviews the evidence on PEP and the need for improved access to PEP in Canada, particularly for gay men

30. 30 30

31. Thank you!