This presentation on PrEP research and policy was given by Dr. Iryna Zablotska, of the Kirby Institute, at the AFAO Members Forum - May 2015.

2. PrEP:
Research update and
implementation program in NSW
Dr. Iryna Zablotska
The Kirby Institute
AFAO, 15 May 2015

3. Start of the PrEP era

4. PrEP effectiveness
a. In intent-to-treat analyses b. In individuals with detectable levels of
TDF/FTC in blood
Source: Plenary presentation by Raphael Landovitz on 23 February 2015

5. What do we know from placebo-
controlled clinical trials of PrEP?
PrEP trials have not seen major short-term issues with:
• Risk compensation
however observation and counselling were intensive, presence of placebo
• Drug resistance
however adherence was too poor to develop drug resistant virus
• Safety and tolerability of Truvada when used by HIV negative
people
however trials enrolled healthy participants, their observation was relatively short
Still need evidence for long-term users of daily PrEP

6. What do we know from placebo-
controlled clinical trials of PrEP?

7. CROI 2015: New evidence from PROUD
• Study aim: To determine whether PrEP worked as well in the
UK as in iPrEx (44% risk reduction in HIV)
• Assumption: effectiveness may be lower in real world because:
– Adherence levels are lower
– Behavior is riskier
• Study design:
– “as close to real world as possible”
– Randomisation to “Truvada now” and “Truvada AFTER 12 months” arms
(randomised treatment stopped in October 2014, all patients continuing on Truvada)
Source: Oral presentation by Chief Investigator Sheena McCormack on 24 February 2015

8. CROI 2015: New evidence from PROUD
STI levels: very high, no difference between study arms
Risk behaviour: no significant difference between arms
Source: Oral presentation by Chief Investigator Sheena McCormack on 24 February 2015

9. CROI 2015: New evidence from iPERGAY
Source: Oral presentation by Chief Investigator Jean Michel Molina on 24 February 2015

10. CROI 2015: New evidence from iPERGAY
• HIV incidence in the placebo arm: higher than expected
• PEP: 48 participants (12%), 25 in the TDF/FTC and 23 in the placebo arm (p=0.73)
• Incidence of STI: very high, no difference between groups
• Sexual behaviour: median # sexual acts/month -10 in both arms, stable,
~70% having unprotected anal intercourse
• Median number of pills/month (IQR): 16 (10-23) in the placebo arm
16 (12-24) in the TDF/FTC arm (p=0.84)
Source: Oral presentation by Chief Investigator Jean Michel Molina on 24 February 2015

11. iPERGAY and PROUD conclusions:
• Both studies enrolled very high risk participants
• HIV incidence in control arms was very high, despite the use of PEP
• STIs: high incidence, no evidence of difference between study arms
• Concerns about PrEP being less effective were unfounded
• Daily PrEP is effective in very high-risk individuals
• Evidence about intermittent (on demand) PrEP insufficient to make
judgement
• CDC Statement on 24 February 2015:
CDC continues to recommend daily dosing of PrEP

12. What does the future hold for PrEP?
Other ongoing trials:
• Alternative schedules of PrEP use – HPTN 069
• Long acting therapies
– Rilpivirine (TMC278) – HPTN 078
– Cabotegravir (GSK1265744) – HPTN 077/ECLAR
• Combinations of interventions

13. Why do we need PrEP?
• PrEP is one of the most efficacious interventions we
have so far
• Ideal prevention intervention for:
– High risk homosexual men
– Injecting drug users
– Some high risk heterosexuals
• Ambitious targets for HIV prevention VS reality
– Global target: reduce sexual transmission by 50% by 2015
and eliminate by 2020
– Reality: In the last decade, increasing HIV incidence in
homosexual men in almost all settings (except San
Francisco, US)

14. PrEP policy in Australia
• Truvada not yet approved by TGA as PrEP (application lodged
by Gilead Sciences in March 2015)
• PrEP Guidelines:
• October 2014 - interim NSW PrEP guidelines (to guide the
NSW PrEP demonstration project PRELUDE)
• February 2015 - national guidelines for PrEP
implementation

15. 16 February 2015: national PrEP guidelines released

16. Defining behavioural eligibility for PrEP: factors associated
with the highest HIV incidence in NSW (HIM study, 2001-2007)
Risk factor Associated HIV incidence
(95% CI)
All patients regardless of practices 0.78 per 100 PY (0.59-1.02)
Regular sexual partner of an HIV-infected man with whom
condoms were not consistently used in the last 3 months
5.36 per 100 PY (2.78-10.25)
>1 episode of receptive unprotected anal intercourse (UAI)
with any casual HIV-infected male partner or a male partner
of unknown HIV status during the last 3 months;
2.31 per 100PY (1.48-3.63)
Rectal gonorrhoea diagnosis 7.01 per 100PY (2.26-21.74)
Rectal chlamydia diagnosis 3.57 per 100PY (1.34-9.52)
Methamphetamine use 1.89 per 100PY (1.25-2.84)
>1 one episode of anal intercourse during the last 3 months
when proper condom use was not achieved (e.g., condoms
slipped off or broke)
1.30 per 100 PY (0.95-1.77)
>1 episode of insertive UAI where the serostatus of partner
was not known or was HIV positive and not on treatment in
the last 3 months
0.94 per 100 PY (0.35-2.52)
- In circumcised men 0.65 per 100PY (0.16-2.61)
- In uncircumcised men 1.73 per 100PY (0.43-6.90)

17. Defining behavioural eligibility: MSM
High risk - recommend prescribing daily PrEP if the client acknowledges:
being likely to have multiple events of unprotected anal intercourse (UAI), (+/-sharing IDU), in the next 3 months (indicating
sustained risk)
AND
Having any of the following:
• Regular sexual partner of an HIV-infected man with whom condoms were not consistently used in the last 3 months (HIV
positive partner is not on treatment and/or has detectable viral load);
• At least one episode of receptive UAI with any casual HIV-infected male partner or a male partner of unknown HIV status
in the last 3 months;
• Rectal gonorrhoea or chlamydia diagnosis during the last 3 months or at screening;
• Methamphetamine use in the last 3 months
Medium risk - consider prescribing daily PrEP if the client acknowledges:
being likely to have multiple events of UAI (+/-sharing IDU) in the next 3 months (indicating sustained risk)
AND
Having any of the following:
• More than one episode of anal intercourse in the last 3 months when proper condom use was not achieved (e.g.,
condoms slipped off or broke);
• if client is uncircumcised and reports more than one episode of insertive CLAI in the last 3 months where the
serostatus of partner was not known or was HIV positive and not on treatment.
Note: MSM who have only infrequent exposures to HIV (e.g., an occasional broken condom or lapse in condom use) may be good candidates for nPEP
rather than PrEP. These men, as well as men who fall into low risk category C, should be educated about safer sex strategies, nPEP and PrEP, and decision
about PrEP use should be made on a case by case basis.

18. Access to and use of PrEP in NSW
I. Informal use
– recorded by Sydney Gay Community Periodic Surveys since 2011 @ about 2.5%
– Schedule of use: unknown
– Sources of medication: varying
II. PrEP demonstration projects
– NSW (300 participants)
– Victoria (100 participants)
– Queensland (50 participants)
III. PrEP prescribing outside demonstration studies
– Levels of prescribing: unknown
– Schedule of use: daily per national guidelines
– Source of medication: purchase online or overseas with self-importation

19. Demonstration project PRELUDE
AIM:
• Develop and evaluate a model of evidence-based delivery of PrEP as part
of HIV prevention strategy in NSW
Progress to date:
• Stage I:
• Sydney Sexual Health (enrolling)
• St Vincent’s Hospital (enrolling)
• Western Sydney Sexual Health Clinic (enrolling)
• RPA Sexual Health (enrolling)
• Stage II:
• Holdsworth House (enrolling)
• Taylor Square (enrolling)
• Newcastle Community Health Services (approval process)
• Clinic 16 (approval process)
• We collect information about all services provided to PrEP users per
guidelines and additional services requested by clinicians (when
necessary) – to assess the amount and cost of services for PrEP users)

20. Demonstration project PRELUDE
AIM:
• Assess the acceptability of PrEP among clients at high risk for HIV (overall
uptake by individuals offered PrEP; reasons for declining PrEP, patterns of
use, self-reported preferences for alternative schedules and/or duration of
PrEP use).
Progress to date:
• # participants enrolled: ~170 out of 300
• First participants reached 6 months of follow-up
• Only 3 people stopped PrEP (all @ 1 month)
• Self-reported willingness to take PrEP for >12 months (at baseline):
96%
• Patterns of use: once daily Truvada pill

21. Demonstration project PRELUDE
• Cohort of very high-risk participants
• Expected HIV incidence (using indicators from HIM study):
1.7 – 7.0 per 100 PY
• Adherence to PrEP and safety issues:
– At this early stage, no major issues with adherence
– No HIV seroconversions
– No drug related serious adverse events
– Most common side-effects: Nausea (7), diarrhea (6), fatigues (6), headache (5) – none that stopped PrEP
– STI incidence:
• Chlamydia detected at baseline – 18, FU1 – 5
• Gonorrhea detected at baseline – 12, FU1 – 0
• Syphilis detected at baseline – 2, FU1 – 1
Important issue to consider in PrEP users: treatment/prophylaxis of STIs

22. Current and future of PrEP in Australia
• Undeniably, PrEP is an efficacious HIV prevention strategy
• Australia is only the 3rd country to have national PrEP guidance
• PrEP is already part of our HIV prevention work
• Strong community advocacy and provider interest to PrEP
• Work is ongoing on establishing and evaluating our new standard of care
PrEP services
• Issues to consider:
• Growing demand for PrEP
• access to and cost of PrEP in Australia

23. Acknowledgements
• Sheena McCormack (PROUD) and Jean-Michel Molina
(iPERGAY) for sharing slides
• PrEP guideline development group (NSW)
• PrEP guideline development group (ASHM)
• NSW Ministry of Health - for funding evaluation research on PrEP
• Gilead Sciences - for providing the study medication TRUVADA
• NSW partner organisations (ACON, Positive Life) – for active
support of PrEP evaluation research
• NSW and ASHM PrEP expert policy development groups
• Clinics participating in the PRELUDE study
• PRELUDE study investigators and management team
• Study participants: PRELUDE study and other research on PrEP