1. Pre-exposure Prophylaxis (PrEP)
Policy, Practice and Politics
Pre-exposure Prophylaxis (PrEP)
Preparing for PrEP
Yasmin Halima
Consultant, AIDS Vaccine Advocacy Coalition (AVAC)
AIDS 2008, Mexico City
3 August 2008

2. Highlight research, policy and political issues
Clinical trials update
Introduce framework for panel discussion

3. Public notices observed in India
In a hotel
You are invited to take advantage of the chambermaid.
At Edwards Laundry
Drop your trousers here for best results.
Please leave your values at the front desk.
On the office door of a gynaecologist
Specialist in women and other diseases. 3

6. What is PrEP and why do we need it?
Pre-exposure prophylaxis (PrEP) involves the use of antiretrovirals to prevent HIV
infection. Unlike post-exposure prophylaxis (PEP), prescribed following potential
exposure to HIV such as a needle-stick injury, or therapy to prevent mother-to-child
transmission, PrEP is intended for use by those who may be at frequent risk for HIV.
Global burden Over 4 million new infections occur every year
To impact the epidemic we have to reduce transmission
Vulnerability to HIV Prevention can protect those most vulnerable
- feminisation of HIV
- IDUs, MSM
Biological plausibility Potential agents and technologies are promising
Lessons learned from PMTCT, PEP

7. Caveats of current research
PrEP trials
Status of research
Caveats of current research
Investment in PrEP

8. Study of daily oral chemoprophylaxis to prevent HIV-1 infection
Design
Phase II/III placebo-controlled randomised trials to determine if daily oral tenofovir (TDF, 300 mg) or TDF and emitricitabine (TDF/FTC, 300 mg mg) prevents HIV-1 acquisition and has acceptable safety in HIV uninfected men and women.
Primary and secondary objectives
Study rates of adverse events in TDF or TDF/FTC arm compared to placebo
Determine if daily PrEP reduces HIV-1 seroincidence
Determine if HBV flares follow cessation of TDF or TDF/FTC
Substudy of changes in bone mineral density or body fat distribution
Evolution of drug resistance in seroconverters
Determine if viral load set point and immune characteristics are affected in seroconverters
Impact on risk behaviors and adherence

10. Caveats and issues related to current research
Test only TDF-based regimens
Test once-daily regimens
Selecting risk groups
If PrEP works, who will pay?
The treatment and prevention dichotomy
Increasing but limited investment in PrEP
Industry commitment?

12. Investment in PrEP research in 2007
CDC $15.6m
Gates $12.56m
USAID $6.0m
NIH $4.1m
Gilead $1.25m

13. Anticipating PrEP
‘For the first time, research that is traditionally thought of by the public as some mystified and esoteric process has immediate relevance and significance to many millions - there is a demand for accountability and transparency for how public funds are being used; a demand to see what scientific priorities are set and how; what scientific progress is being made and at what pace; a demand for findings from studies to be translated into policy and practice.
As scientists we would do well to pause and reflect on this.’
Quarraisha Abdool Karim, University of KwaZulu Natal, South Africa

14. Courage is what it takes to stand up and speak.
Engaging with PrEP
Courage is what it takes to stand up and speak.
Courage is also what it takes to sit down and listen.
Winston Churchill

15. Thank you

16. Assumptions for hypothetical scenarios
Size n = 3,000
Trial designed to test efficacy of 70%
Lower range of CI 30%
SOC for prevention includes regular counselling, male/female condoms
Toxicity monitoring includes HBV, bone-mineral density, renal, hepatic impairments
Primary endpoints are efficacy and safety; protect against HIV; safe to use on daily basis
Secondary endpoints are lower viral set point, higher CD4, viral resistance and behaviour changes
HIV testing conducted monthly
Resistance testing as follow-up for all seroconverters
Post-trial care includes 1 yr provision of PrEP if proven effective for those who do not seroconvert

17. Results from a PrEP trial testing Truvada (TDF/FTC)
Scenario 1
Results from a PrEP trial testing Truvada (TDF/FTC)
shows that it is 70% effective at reducing acquisition of
HIV in this group.

18. Results from a PrEP trial testing TDF show that it is
Scenario 2
Results from a PrEP trial testing TDF show that it is
50% effective at reducing acquisition of HIV in injecting
drug users (IDU) when tested as directly-observed
therapy (DOT).

19. Results from a PrEP trial testing Truvada (TDF/FTC)
Scenario 3
Results from a PrEP trial testing Truvada (TDF/FTC)
show that it is 70% effective at reducing acquisition of
HIV in a heterosexual group of young men and
women.
However, 2% of those who seroconverted in
the trial demonstrated resistance with K65R mutation.