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 jwilton@catie.ca 1

HIV/AIDS in Canada Number of people living with HIV 2 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

Improving HIV prevention 3 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

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

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 48-72 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

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”

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

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

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

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%

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

CATIE’s Programming Connection

CATIE Resources: PEP factsheet and article

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

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Thank you!