Associate Prof. Dr. Jason Ong STI incidence and prevalence in PrEP programmes – highlights from a systematic review Associate Prof. Dr. Jason Ong

Acknowledgements LSHTM Philippe Mayaud, Fern Terris-Prestholt, Joseph Tucker, Sabrina Rafael, Vanessa Anglade, Jane Falconer East Virginia Medical School Hongyun Fu University of Minnesota Twin Cities Kumi Smith WHO Rachel Baggaley, Teodora Wi, Ioannis Mameletzis, Michelle Rodolph Acknowledgements jason.ong@lshtm.ac.uk

All investigators state they do not have any conflicts of interest Funding from WHO HIV department to conduct the systematic review Conflicts of interest jason.ong@lshtm.ac.uk

Background Aims Outline Methods Key messages Full paper has been submitted - jason.ong@lshtm.ac.uk

BACKGROUND

PrEP works! i.e. safe and effective (esp when adherence is high) 1-4 WHO advocates PrEP for those with HIV incidence > 3 per 100 PY 5 1 Cohen (2011) NEJM 365(6):493-505 2 Grant (2010) NEJM 363(27):2587-99 3 McCormack (2016) The Lancet 387(10013):53-60 4 Molina (2015) NEJM 373(23):2237-46 5 https://www.who.int/hiv/pub/prep/policy-brief-prep- 2015/en/ Background jason.ong@lshtm.ac.uk

Background Concern about rising incidence/prevalence of STIs globally High incidence/prevalence of STIs in PrEP users 1-3 “Risk compensation” 4,5 Antimicrobial resistance 1 Liu. (2016) JAMA Intern Med 176:75-84 2 Kojima (2016) AIDS 30:2251-2 3 Traeger (2018) CID 67(5):676-86 4 Blumenthal (2014) Virtual Mentor 16(11):909-15 5 Hojilla (2016) AIDS Behav. 20(7):1461-1469 jason.ong@lshtm.ac.uk

Background Is PrEP contributing to this? Can PrEP programs be harnessed to help mitigate these upward trends in STIs? Is PrEP contributing to this? Leads to behavioural changes i.e. more condomless sex? Rising STI rates before PrEP implementation Can PrEP programs be harnessed to help mitigate these upward trends in STIs? Attracting groups already at high risk for STIs Background jason.ong@lshtm.ac.uk

Could PrEP progams be a gateway for empowering comprehensive sexual health services? Caveat that in some settings – PrEP is integrated into strong sexual health services … will discuss models later… jason.ong@lshtm.ac.uk

AIMS

Determine baseline STI prevalence of PrEP users Need for better STI services? Determine incidence of STIs during PrEP use Ongoing high risk of STIs? Aims jason.ong@lshtm.ac.uk

METHODS

Methods 2 sources of data Systematic literature review Directly from PrEP implementers Methods jason.ong@lshtm.ac.uk

Methods – systematic review 9 databases searched Two key concepts: (STIs) and (PrEP) Followed procedures as per Cochrane Handbook 5.1 Methods – systematic review jason.ong@lshtm.ac.uk

Methods – systematic review Inclusion RCTs Observational/demonstrati on projects Report on at least one of: Lab-confirmed STI incidence/prevalence Cost measures Description of program to test STI Methods – systematic review jason.ong@lshtm.ac.uk

Methods – systematic review Pathogens Chlamydia trachomatis Neisseria gonorrhoeae Treponema pallidum Hepatitis A/B/C Trichomonas vaginalis Mycoplasma genitalium Herpes simplex virus Methods – systematic review jason.ong@lshtm.ac.uk

Methods – systematic review Exclusion Systematic reviews/Letter/editorials Qualitative research about outcomes Studies restricting study population e.g. men with urethritis, women with cervicitis (No language or time restrictions) PROSPERO registration: CRD42018116721 Methods – systematic review jason.ong@lshtm.ac.uk

Methods – systematic review Meta-analysis using random effects model Prevalence at baseline Incidence during PrEP use Subgroup meta-analysis and meta-regression Methods – systematic review jason.ong@lshtm.ac.uk

Methods – Data from PrEP implementers Email sent 14th December 2018 to 82 contacts 45 indicated willingness to share data 25 sent data by deadline (31st Jan 2019) Data requested In any form related to STI prevalence/incidence in PrEP users, STI services Survey jason.ong@lshtm.ac.uk

RESULTS

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Countries with PrEP programs (PrEP Watch) jason.ong@lshtm.ac.uk

jason.ong@lshtm.ac.uk

Pooled STI prevalence at baseline   Our study Global estimates 2016 Pathogen Weighted average (95% CI) Men Women Chlamydia 10.8 (6.4-16.1) 2.7 (1.9-3.7) 3.8 (3.3-4.5) Gonorrhoea 11.6 (7.6-16.2) 0.7 (0.5-1.1) 0.9 (0.7-1.1) Early syphilis 5.0 (3.1-7.4) 0.5 (0.4-0.6) Hepatitis A 5.4 (4.1-7.0) Hepatitis B 1.3 (0.1-3.5) Hepatitis C 2.0 (0.8-3.7) Any Ct/Ng/Tp 23.9 (18.6-29.6) jason.ong@lshtm.ac.uk

Pooled STI prevalence at baseline   Our study Global estimates 2016 Pathogen Pooled prevalence (95% CI) Men Women Chlamydia 10.8 (6.4-16.1) 2.7 (1.9-3.7) 3.8 (3.3-4.5) Gonorrhoea 11.6 (7.6-16.2) 0.7 (0.5-1.1) 0.9 (0.7-1.1) Early syphilis 5.0 (3.1-7.4) 0.5 (0.4-0.6) Hepatitis A 5.4 (4.1-7.0) Hepatitis B 1.3 (0.1-3.5) Hepatitis C 2.0 (0.8-3.7) Any Ct/Ng/Tp 23.9 (18.6-29.6) jason.ong@lshtm.ac.uk

Paper’s appendices Subgroup analyses Meta-regression Pathogen Anatomical site (Pharyngeal vs. Rectal vs. urethral) Subpopulations (MSM only vs. mixed) Type of study (Routine vs. “trial”) World Bank Income group (High-income vs. LMIC) Meta-regression Funnel plots/Egger’s test jason.ong@lshtm.ac.uk

Gonorrhoea prevalence by anatomical site

Gonorrhoea prevalence by country income level jason.ong@lshtm.ac.uk

Gonorrhoea prevalence by study type jason.ong@lshtm.ac.uk

Meta-regression results for the predictors of gonorrhoea prevalence Characteristic Variable OR (95% CI) p value AOR (95% CI) Anatomical site Oral 1   All sites 1.06 (1.00-1.11) 0.05 1.08 (0.99-1.18) 0.09 Genital 0.92 (0.86-0.99) 0.02 0.97 (0.88-1.07) 0.57 Anorectal 1.02 (0.95-1.09) 0.63 1.05 (0.95-1.16) 0.35 Population Mixed MSM only 1.02 (0.94-1.10) 0.66 1.11 (1.00-1.22) 0.04 Country income level LMIC High 1.01 (0.95-1.07) 0.74 0.97 (0.91-1.03) 0.26 Study type Routine RCT 0.96 (0.89-1.02) 0.18 0.94 (0.85-1.04) 0.22 Cohort 1.00 (0.94-1.06) 0.95 0.96 (0.87-1.05) 0.33 Demonstration 0.73 0.52

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Pooled STI incidence Our study Global estimates 2016 Pathogen   Our study Global estimates 2016 Pathogen Pooled incidence per 100 PY (95% CI) Men Women Chlamydia 21.5 (17.9-25.8) 3.3 (2.1-4.8) 3.4 (2.5-4.5) Gonorrhoea 37.1 (18.3-25.5) 2.6 (1.5-4.1) 2.0 (1.4-2.8) Early syphilis 11.6 (9.2-14.6) 0.2 (0.1-0.2) Hepatitis A - Hepatitis B 1.2 (0.6-2.6) Hepatitis C 0.3 (0.1-0.9) Any Ct/Ng/Tp 72.2 (60.5-86.2) jason.ong@lshtm.ac.uk

Pooled STI incidence Our study Global estimates 2016 Pathogen   Our study Global estimates 2016 Pathogen Pooled incidence per 100 PY (95% CI) Men Women Chlamydia 21.5 (17.9-25.8) 3.3 (2.1-4.8) 3.4 (2.5-4.5) Gonorrhoea 37.1 (18.3-25.5) 2.6 (1.5-4.1) 2.0 (1.4-2.8) Early syphilis 11.6 (9.2-14.6) 0.2 (0.1-0.2) Hepatitis A - Hepatitis B 1.2 (0.6-2.6) Hepatitis C 0.3 (0.1-0.9) Any Ct/Ng/Tp 72.2 (60.5-86.2) jason.ong@lshtm.ac.uk

Limitations Most STI data were from high income countries Data gaps from major parts of the world – be careful about extrapolation Selection bias rectal STI may be a inclusion criteria e.g. some US programs Others did not – NSW-EPIC Detection bias for incidence rates More frequent STI screening in PrEP users Limitations jason.ong@lshtm.ac.uk

Limitations Lack of uniform measures in reporting (esp. incidence) By pathogen, subpopulations Inaccessible data A lot of data out there Many are still behind “locked” doors – needing ethics or not easily obtained by implementers Limitations jason.ong@lshtm.ac.uk

Key messages jason.ong@lshtm.ac.uk

Key messages Incredibly high burden of STIs (compared to non- PrEP) Prevalence and incidence Key messages jason.ong@lshtm.ac.uk

And also have ongoing risk for STIs We have an opportunity PrEP is attracting people with behaviors that put them at high risk for HIV/STIs And also have ongoing risk for STIs So, ‘basic’ STI services for prevention, early detection and Rx of STIs should be a priority Ideally extra-genital testing Ct/Ng (Mg) jason.ong@lshtm.ac.uk

STI service models in PrEP programs PrEP services with Rapid or POCT for STI UK – Dean St Express PrEP integrated into STI services UK, Australia Multi-site Ct/Ng screening PrEP services with minimal STI screening Japan, Brazil, Thailand Syphilis only Often no CT/NG screening due to costs PrEP services with syndromic management +/- presumptive treatment South Africa, Kenya PrEP services with referral to another clinic sites STI services Thailand (some sites) PrEP services with no STI service jason.ong@lshtm.ac.uk

Barriers/Facilitators for providing STI services for PrEP users Barriers/Challenges STI diagnostics PrEP program logistics STI capacity building Facilitators Money Training Research jason.ong@lshtm.ac.uk

PrEP programs can be a gateway for empowering comprehensive sexual health services Caveat that in some settings – PrEP is integrated into strong sexual health services … will discuss models later… jason.ong@lshtm.ac.uk

Thank you Finally I want to thank you for your attention.