Anne Robertson, Sexual Health Physician, MidCentral Health, New Zealand

1. Pre-exposure prophylaxis
Sexually Transmitted Infections
Anne Robertson
Sexual Health Physician, MidCentral Health, New Zealand

2. Aotearoa New Zealand
MidCentral Health (Palmerston North)
Home base – population 174 000
Wider services – population 398 000
(Hawkes Bay and Whanganui)

3. Overview
• The rationale for PreP for STIs
• The current use of antibiotics in STI disease control
• Pilot study evidence
• The questions and challenges
• PrEP as part of wider STI control strategies

4. Why consider PrEP for STIs?

5. Current strategies for STIs have had only had
modest impact
• Behavioural interventions
• Integration of services into primary care settings to improve access
• Evidence based guidelines
• Chlamydia screening programmes and strategies
• Mass treatment
• Multiple component population level interventions (PREVEN, Peru)
• Efforts hampered by difficulties in addressing social determinants

6. Chlamydia testing programmes
• Leaky bucket if emphasis on testing
and not good case management
(Woodhall, Saunders UK)
• NZ data has shown similar pattern for
integrated services – appear
successful in project phase but poor
STI case management when business
as usual
• New biomedical approach for STI
disease control required

7. PrEP for HIV – an apparent success story
• The use of tenofovir 300mg/emtricitabine 200mg daily prior to exposure to
possible HIV
• Initial studies showed mixed results but subsequently demonstrated that
when people are motivated to take PreP, it works (e.g Iprex and PROUD/
Ipergay – different study design but similar results with 86% reduction )
• Implementation of pre-exposure prophylaxis for HIV programmes in
conjunction with treatment as prevention and improved testing has led to
a reduction in new HIV notifications
• But rapid rise in bacterial infections – decoupling of HIV and STI prevention

8. PreP works for HIV so why not for
STIs?

9. QUESTIONS
• PrEP works for HIV so can pre-exposure antibiotic prophylaxis work
for the prevention of sexually transmitted infections?
• If it works, does the risk of prophylactic antibiotic prophylaxis on the
development of antimicrobial resistance outweigh the benefits of
prevention?

10. Widespread use of antibiotics for infection
control is not new
• For non STI disease control
• malaria control (prophylaxis)
• Prevention of surgical infections (prophylaxis)
• Yaws, trachoma eradication (mass treatment)
• For STI disease control in populations where only a certain % are
infected
• Syndromic management
• Empirical treatment
• Partner management
• Mass treatment strategies
• Post exposure prophylaxis (sexual assault)(Ipergay study)

11. Back to Basics - The Reproduction Number
Ro = βcD
Ro = reproduction no. or no. of secondary cases generated from 1
infected individual in a fully susceptible population
β = transmission co-efficient
C = pattern of contact between infected and susceptible
D = duration of infection

12. • By altering β, the ability to transmit, D the duration of infectivity and c
the number of infected contacts
Ro will fall
It should be noted that for some of the interventions the focus was on
reducing inflammation from STIs to reduce HIV transmission with
reduction in STI case notifications being a secondary aim

13. Population level strategies – mixed results
and much debate
• Apparent success of Mwanza study (Tanazania) vs Rakai and Masaka
(Uganda)
• Different approaches (mass rx, strengthened syndromic management,
+/- behavioural intervention) and different results
• Mwanza apparent decrease in HIV incidence out of proportion to STI
reduction
• A number of reasons given for different outcomes:
• Different phases of HIV epidemic, differences in risk behaviours, ?contribution
of rural and roadside communities
• Need to consider context when implementing and evaluating
strategies

14. Meta-analysis of potential effect of biomedical
interventions on STI prevalence (Ng (Cochrane), 2011)
• Combined mass treatment and strengthened STI management data:
• Reduction in syphilis 12%
• Reduction in gonorrhoea 51%
• No effect on chlamydia
• With current increase in antimicrobial resistance to NG can effect on
gonorrhoea be maintained?

15. Mass trachoma treatment strategy
• Mass drug administration of azithromycin for trachoma reduces the
prevalence of genital Chlamydia trachomatis infection in the Solomon
Islands
• 40% reduction in age adjusted genital Chlamydia trachomatis with no
impact on Neisseria gonorrhoeae in survey group of women
• Marks M, Bottomley C, Tome H, et al. Sex Transm Infect 2016;92:261–
265.

16. Mass treatment of syphilis outbreak (Canada)
• British Colombia
• Heterosexual outbreak
• No sustained effect
• Rekart, 2003

17. Evidence for PreP for STIs

18. A small randomised pilot study (Bolan, 2015)
• 30 HIV positive MSM with history of syphilis x 2 randomised
• 2 arms – doxycycline for 36 weeks vs contingency management (CM -
financial incentive to stay STI free)
• Tested for bacterial STIs at weeks 12, 24, 36 and 48
• Reduced incidence of STIs in intervention group despite no
differences in behavioural risk (OR 0.27, p=0.02)
• Doxycyline 100mg single daily dose, adherence assessed by blood
concentration
• The majority were adherent with 1 discontinuation (reflux)

19. Bolan contd.
• Syphilis 2 cases in rx group vs 6 in CM
• 6/53 visits associated with STDs (chlamydia, NG, syphilis) in rx group
vs 15/49 in CM group
• Statistical difference at 48 weeks (beyond cessation of rx)
• ?continued rx in active arm
• Weakness of study was that doxycycline levels not measured in CM
group

20. Potential choices of agent?
• Doxycyline
• little evidence of chlamydia or syphilis resistance to doxycycline
• Not used for NG rx
• Not considered effective for Mycoplasma genitalium rx despite lack of in vitro
resistance
• But ?impact of effect on gut flora
• What dose should be used?
• Not known what dose of doxycycline effective against syphilis
• Half life of 12 hrs but once daily dose gave levels of 1000-4000 ng/ml

21. Choice of antimicrobials
• Azithromycin
• Used in non-STI mass rx disease eradication
• Concerns re emerging resistance in NG and Mycoplasma genitalium
• Shift in microbiome composition with long term persistence of resistant
strains
• Fluoroquinolones
• High level resistance and ecological impact

22. Other questions (Dubourg, Raoult, 2016)
• ?Inclusion in MSM PrEP programmes
• But increase in bacterial STIs not restricted to MSM community
• Youth - students
• Correctional facilities
• Military
• Overseas travel
• Impact on extra-genital infections in non-MSM
• ?Strategies for Neisseria gonorrhoeae
• ?Antiseptic mouth rinses (Chow)

23. Comparison of PrEP for HIV and PrEP for STIs
PrEP for HIV PrEP for STIs
Of proven benefit ?Of modest benefit only
Prevents HIV and Hepatitis B Potential action against multiple infections –
?synergies or ?negative impacts on other infections
Political support in principle to reduce new HIV
infections although PrEP not currently funded in most
jurisdictions
Little political will
Strong advocacy – HIV high profile Little advocacy support - STIs low profile at both
community and national level
Easy to demonstrate potential cost effectiveness
despite moderately high cost
Inexpensive but harder to provide cost effectiveness
data
Low risk of antiviral resistance unless missed early
seroconversion
Effect on resistance and microbiome to be evaluated
Challenge of maintaining monitoring standards when
rolled out to wider range of providers
Easily prescribed in all health care settings but
challenge of monitoring population level impact

24. CONCLUSION
• There is a need for new interventions to combat rising rates of bacterial
STIs
• Following on from the success of Pre-exposure prophylaxis for HIV, PrEP for
STIs is worthy of consideration
• Evidence for PrEP for STIs is only emerging – more in pipeline
• Initial evidence suggests modest rather than dramatic effect for syphilis
and ?chlamydia
• Any PreP for STI programme requires careful implementation with
consideration of:
• Who to target
• How to monitor and evaluate – effect on antimicrobial resistance and microbiome

25. Conclusion continued
• Implementation of PreP for STIs requires to be considered as part of
the broader strategy for STI prevention
• Five strategic directions underpin the Global STI Strategy.
• Information for focused action
• Interventions for impact
• Delivering for equity
• Financing for sustainability
• Innovation for acceleration.
• But PrEP for STIs may contribute to achieving one of the Strategy
targets of a 90% reduction in Treponema pallidum incidence by 2030

27. Any questions?