This presentation was given by Dr Dan Clutterbuck of NHS Lothian and NHS Borders, at the HIV Scotland 'PrEP Roundtable Discussion' event on 25 August 2015.

1. PrEP: Clinical Perspectives
Dr Dan Clutterbuck
Consultant in Genitourinary & HIV medicine
NHS Lothian

2. What we know
…and don’t know
• PrEP Studies
• PROUD Study
• IPERGAY
• Partners PrEP Demonstration project
• Some questions

3. PrEP Studies
• 10 studies of PrEP: 7 showed effect
– 3 trials of oral TFV/FTC in MSM
– 1 trial of oral TFV/FTC in heterosexual men and women
– 2 of oral TFV alone in young heterosexuals and in IVDU
– 1 of TFV 1% vaginal gel
• 3 others showed no benefit (oral Tenofovir, Truvada, Tenofovir vaginal gel
in women in sub-saharan Africa)
• Adherence is everything
• Adherence needs to be higher in women than in MSM

4. The PROUD pilot
• Randomised controlled pilot trial.
• PRe-exposure Option for reducing HIV in the UK
• To assess recruitment, adherence, feasibility
• Not powered to show a difference in HIV incidence between
groups
• Assumed an HIV seroconversion rate of 3% in the deferred
arm
• Immediate PrEP vs PrEP delayed for 1 year

5. Study outline
• Intended as a ‘Real life’ study
• Eligibility: MSM who had had condomless anal sex in the last
3 months (insertive and/or receptive) and thought likely to do
so again
• Randomised to receive Truvada one tablet daily immediately,
or in one year’s time
• Baseline and 3 monthly HIV test, U+Es, STI screen,
behavioural questionnaire

6. Results
• 22 HIV seroconversions: 3 in immediate and 19 in deferred arm.
• 92% retained in the immediate group and 88% in the deferred group
(remarkable)
• Equates to 1.3 seroconversions per year in immediate group vs 8.9 per
year in deferred group – an 86% reduction in incidence (p=0.0002)
• The number needed to treat for one year to prevent 1 infection was 13
• High risk men can self-select for PrEP

7. PROUD findings
• Men who seroconverted on PrEP:
– Strong suggestion that they were not taking ART when they acquired
infection.
• Behavioural risk compensation
– Slightly more STIs in immediate than deferred group (57% vs 50%) –
but they had more STI screens
– No difference in rectal STIs (35% vs 32%)
– BUT an upward shift in the proportion of men who had 10 or more
UPAI partners
– And a VERY high rate of STIs

8. Ipergay
• Intervention Préventive de l'Exposition aux Risques avec et
pour les hommes Gays
• Randomised placebo controlled trial
• Truvada vs placebo tablets
• ‘On demand’ dosing
– Double dose Truvada 2-24 hours before sex
– Then one dose every day of unprotected sex until the day
after the last exposure

9. Results
• 445 men recruited (less than planned because of PROUD
results)
• 16 HIV seroconversions. 2 in the Truvada arm and 14 in the
placebo arm.
• Equates to 0.9 seroconversions per year in immediate group
vs 6.6 per year in deferred group – an 86% reduction in
incidence (p=0.0002)
• The number needed to treat for one year to prevent 1
infection was 18

10. Other issues - Ipergay
• Median adherence 16 pills a month, used correctly at 43% of
sexual exposures reported
• About half the number of doses of Truvada than in PROUD
• What does this mean for intermittent use at <4 doses per
week?

11. Partners PrEP Demonstration
• Enrolled 1,013 heterosexual serodiscordant couples in Uganda and Kenya
• “Higher risk”= Risk factors (such as younger age, reporting condomless sex
in the last month, or higher viral loads in the HIV-positive partner) that
might make transmission more likely
• PrEP for HIV-negative partner only until the HIV-positive partner on ART
for six months
• Two HIV transmissions occurred compared to historical controls (data
from previous studies of serodiscordant couples predicting 39.7 HIV
infections)
• A 96% reduction in transmissions
• Neither had detectable tenofovir levels in their plasma samples taken
when tested positive.

12. Questions for clinicians
• To what extent will PrEP be NHS funded?
– According to PROUD criteria
– More restrictive criteria?
• Cost effectiveness
– Depends on generic drugs (Truvada out of license 2016)
– Depends on frequency (Ipergay vs PROUD daily dosage)
• Access to therapy
– On line purchase – private prescriptions
– Licensing and regulation
– Misappropriation of prescribed drugs (ART,PEP)
– Supervision and monitoring for those who have purchased drugs

13. Supply questions
• Safety and cost of supply
– Aidsdrugsonline: $115 for Tenvir EM 200/300 30 tablets
– Other online suppliers: $70
• Awareness and securing equity of access
– 50% of MSM aware of PrEP
– Lower awareness among other groups
– Most studies >50% highly educated

14. Clinical questions
• How much is enough?
– Ipergay average 4 tablets a week
– What if you use less frequently?
• How many is enough?
– Tenofovir alone effective in heterosexual men and women
and IVDU
• How soon is enough?
– 2 hours before sex provides emtricitabine alone

15. Other issues
• Effect on rates of other STIs (more UPAI)
• STIs in men not using PrEP
• Clinic capacity: 3 monthly follow up
• Duration of PrEP