Prof. Mufuta Tshimanga Co-Principal Investigator PrePex Device for Rapid Scale up of Male Circumcision Programmes in Zimbabwe: Results of 3 Studies Prof. Mufuta Tshimanga Co-Principal Investigator

Background Zimbabwe started VMMC programme in mid 2009 Part of a comprehensive HIV prevention programme Phased approach with learning phase Different models of service delivery, integrated, fixed, outreach and mobile services Target: 1.3 Million , 80% of 13-29 age group by 2015, reached 75,000 since inception MOHCW interested in innovative models to increase scale up of VMMC MOVE Adult male circumcision devices, such as PrePex To increase the feasibility of accomplishing this target, MOHCW has been interested in a non-surgical circumcision device such as PrePex Device for scaling up male circumcision

Trial Phases Each phase examines safety and acceptability Phase 1 - Safety and Efficacy study Phase 2- RCT surgery vs device Phase 3 - Field studies  Each phase examines safety and acceptability

Inclusion Criteria Procedures Above 18 years Agrees to be circumcised by any of the study methods, PrePex or Surgical, accepts study procedures and requirements HIV sero-negative Procedures Screening Psychosocial Interview Deployment of Device Removal of Device Follow-up visits to day 90

Safety Study One arm, open label, prospective study to assess safety and efficacy 53 Men Overall procedure duration was 11 minutes 33 sec (SD=3.19 min) for deployment and removal Median time for complete healing was 35 days post device removal No SAE recorded

Safety Study-Pain Scores Time VAS Scale Pain N Level 0 Level 2 Level 4 During device Placement 53 48 (90.6%) 5 (9.4) 3 hours post-Placement 53 (100%) 2 days post-Placement 33 (62.3%) 19 (35.8%) 1 (1.9%) Before device and foreskin removal 52 27 (50.9%) 21 (39.6%) 4 (7.5%) During device removal 26 (50.0%) 25(48.1%) 1 minute post-device removal 12 (23.1%) 38 (73.1%) 2 (3.8%) 2 week post-device removal 48 43 (89.6%) 4 (8.3%) 1 (2.1%)

Safety Study Acceptability All participants were satisfied with the circumcision procedure and the aesthetic result 90 days post-procedure 55.5% stated the abstinence period as too long

Comparative Study - Design RCT comparing PrePex (n=160) to Forceps Guided Surgery (n=80) Compare the surgery and PrePex : Procedure time Time to complete healing Costing

Comparative Study-Results Surgical MC Prepex MC ( placement and removal) Median Procedure Time* 15.3 Min (Q1=15.3, Q3=23.9) 4.6 Min (Q1=4.0, Q3=5.8) Time to complete healing (Median) 42 days (Q1=42, Q3=42) 35 days (Q1=35, Q3=42) Include timing of each step of the procedure *p<0.001

Ongoing Field Study One arm, open label, prospective, cohort field study, 600 participants Assess safety of PrePex when circumcision is performed by nurses Evaluate PrePex training needs Evaluate acceptability of PrePex by patients, partners and care givers Evaluate the effectiveness and cost-effectiveness of the PrePex device

Field Study-Preliminary Results Recruitment started 9th May, 2012 at 3 study sites 750 devices were successfully deployed and removed by Nurses 150 during training phase Recruitment completed 9th July, 2012 No SAE recorded Follow up visits, to end on 16 Oct, 2012

Conclusions PrePex device is safe to use for MC delivered by physicians and nurses Pain related to PrePex appears to be minor Our findings reaffirm and validate similar clinical studies on PrePex done in Rwanda

Investigators Dr Gerald Gwinji, MBChB, MPH. PS MoHCW, Principal Investigator Prof Mufuta Tshimanga, MD; Department of Community Medicine, University of Zimbabwe, Co-Principal Investigator Dr. Tonderai Mangwiro,MMed Urology, Department of Surgery, University of Zimbabwe Dr. Owen Mugurungi, MBChB, Msc; Director AIDS /TB unit , MoHCW Dr. Munyaradzi Murwira, MBChB, MPH, Director ZNFPC Dr. Dan Montano, PhD, Batelle Memorial Institute Dr. Danuta Kasprzyk, PhD, Batelle Memorial Institute Mrs. Daisy Nyamukapa, Program Officer, UNFPA Mr. Sinokuthemba Xaba, MC Program Officer, MOHCW Dr Karin Hatzold, MD, MPH, Deputy Director SRH, HIV &TB, PSI Dr Christopher Samkange, Director ICHE, College of Health Sciences, University of Zimbabwe

Acknowledgements MoHCW ZNFPC UNFPA Gates Foundation PSI ZiCHIRe

Summary of Scientific Validation and Implementation of PrePex for Non-Surgical Adult Male Circumcision MUTABAZI Vincent Rwanda Ministry of Health AIDS 2012 Conference July 22nd-27th , 2012

Background Rwanda has a national goal to significantly decrease its HIV incidence rate, by launching a VMMC to reach 2 million adults in 2 years as part of a comprehensive HIV prevention strategy.  WHO TAG recommendation to scale up PrePex MC in Rwanda received in March 2012.

PrePex Innovation Non Surgical MC No injected anesthesia Bloodless procedure No sutures No sterile settings FDA approved, CE Mark

PrePex Placement Procedure Disinfection Measuring Marking the Circumcision Line Applying Cream Apply the Placement Ring Inserting the Inner Ring Aligning Placement Ring to the Inner Ring and Adjusting the Foreskin Elastic Ring Over the Inner Ring – Creates Pressure on the Foreskin

PrePex Removal Procedure Disinfection Measuring Marking the Circumcision Line Applying Cream Apply the Placement Ring Inserting the Inner Ring Aligning Placement Ring to the Inner Ring and Adjusting the Foreskin Elastic Ring Over the Inner Ring – Creates Pressure on the Foreskin

Clinical Roadmap Clinical studies of PrePex were planned using the WHO Evaluation Framework of Adult MC Devices. PrePex Safety & Efficacy Study - 105 subjects, including first cases of natural detachment by day 15 that was found to be safe Visited onsite by WHO, Gates. Manuscript Published in JAIDS. CROI, AUA Comparison Study – 144 PrePex/73 Surgery Audited onsite by WHO, USAID. Manuscript accepted (not yet published) to JAIDS Nurses Feasibility Study – 49 subjects, 6 nurses Nurses cohort Study – 590 subjects, 10 nurses Oral Presentation in ICASA Dec 2011, IAS 2012

PrePex Center of Excellence 6 physicians and 41 nurses were successfully trained as PrePex operators in Rwanda. Teams from Zimbabwe were trained by Rwanda. Hosted delegations from Uganda, Botswana, USA and more in 2012. 1 paper published, 1 accepted, 1 under review and 2 in writing. PrePex Train the Trainer available to train Sub-Saharan Africa. Gates Foundation to sponsor capacity building for PrePex Center of Excellence.

First Steps Towards Scale-up Hearts & Hands Campaign (June 2012) – Sponsored by Korean NGO, 6 nurses from Byumba hospital (rural),1,000 successful MC within 3 weeks with a total of 7 mild AEs, (0.7%). The campaign was closely supervised by MoH, physicians and nurses from PrePex Center of Excellence, All AEs gathered and analyzed. Army Week Campaign (July 2012) – Sponsored by the Rwanda Military Hospital, 7 teams of nurses performed 1,500 procedures within two weeks on 8 rural health centers across the Cyangugu district. Closely supervised for AEs, 6 mild AEs, AE rate 0.4%. Operational Pilot Demonstration (Q3 2012) – Sponsored by Global Fund and Bill & Melinda Gates Foundation. Defining parameters for scale up and studying removal with one nurse and AE monitoring for scale up. 10,000 clients.

Key Takeaways SAFE: Very low AE rate demonstrating high safety of PrePex by nurses. 18 related AES from total of 4166 procedures (0.46%) EASY TO TRAIN: Nurses with no prior knowledge, can be trained in 3 days course to perform Safe, Effective and Efficient MC. Proper supervision is important to ensure safe implementation before releasing to the field. NATURAL DETACHMENT – a pre-safety study was conducted in March 2009, to alleviate concerns about men not returning for removal. The outcome assured us that PrePex was safe, and would naturally detach for complete circumcision, if men did not come back to the clinic.

Next Steps Scale up – Q3 2012 Rwanda plans to initiate scale up program Pilot of 10,000 to inform scale up (Global Fund, Gates) 2 Million MCs in 2 years ~150 teams of 2 nurses (full time – 8 hours a day) 54 procedures per team per day (Placement +Removal) 4000 MCs Per day (4000 placements 4000 removals) 250 working days per year Adolescents study – 10 to 17 years old

Thank You