1. RTI International RTI International is a trade name of Research Triangle Institute. www.rti.org Vaginal Ring Adherence in sub-Saharan Africa: expulsion, removal and perfect use Presented by: Elizabeth T. Montgomery IAS Conference on Pathogenesis, Treatment and Prevention Rome, Italy July 18, 2011

2. RTI International Co-Authors and Partner Institutions  International Partnership for Microbicides – Cynthia Woodsong – Katherine Young – Joseph Romano – Annalene Nel – Claire von Mollendorf (PI)  Medical Research Council, Durban, South Africa – Shay Ganesh  RTI International, San Francisco, USA – Ariane van der Straten – Helen Cheng – Lynn Wegner  KCMC Tanzania – Gileard Masenga  Univ of Cape Town – Linda-Gail Bekker  WRHI – Helen Rees

3. RTI International Background  Promising antiretroviral-based microbicide candidates are being formulated for delivery in vaginal rings for female-initiated HIV prevention.  A critical advantage of rings over other microbicide delivery mechanisms is that they can be continuously worn, and are thus both coitally-independent and require minimal user action.

4. RTI International Methods I: Study Design  International Partnership for Microbicides, IPM 011 Study  Open-label, randomized crossover design – 12 weeks of placebo ring, 12 weeks of no product, or vice versa  Study Sites in Tanzania (1) and South Africa (3) – N = 170

5. RTI International Study Product  Off-white, flexible vaginal ring  Tin-catalyzed, silicone elastomer matrix  56 mm outer diameter; 7.7 mm cross-sectional diameter  Intended for monthly use

6. RTI International Adherence Study Objectives  To measure adherence to ring use  To quantify ring expulsions and removals and to describe circumstances surrounding these events

7. RTI International Adherence Measures  Adherence assessed every 4 weeks during 12 weeks of ring use – Self-reported use; face-to-face Adherence Interview – Pharmacy records (data not shown here)  Expulsions: voluntary and involuntary  Adherence level: – Perfect adherence: VR never came out during 12 weeks of ring-use – Monthly adherence: proportion of whole or partial days (>12 hours) participants wore the VR in each visit interval.  80% adherent VR was in the vagina for ≥80% days (or partial days)  100% adherent VR was in the vagina for 100% days (or partial days)

8. RTI International Analysis  Quantitative Analysis – Frequencies and circumstances of ring expulsion or removal quantitatively tabulated – Predictors of “perfect adherence” were modeled using multivariable logistic regression.  Qualitative – 6 Exit focus group discussions (FGD) with 48 female participants and 19 male partners interviews (MPI). – Data coded and analyzed using Nvivo software.

9. RTI International Results 1: Study sample  Analytic sample n = 157  Mean age of 27 (Range: 18-35)  Majority (70%) unmarried  Almost three-quarters (72%) had more than 1 partner within three months prior to enrollment  82% ever-used male condom  30% had ever used vaginal products for any reason

10. RTI International Ring Removals  34 ring removals were reported by 28 participants (18%)  Evenly attributed to voluntary and involuntary circumstances Week 4Week 8Week 12TOTAL Voluntary67316 (47%) Involuntary84517 (50%) Unknown0101 (3%) TOTAL1412834

11. RTI International Reasons for Removal  Involuntary – Menses-related most common – Removals associated with defecation, urination, or sex were described less frequently  Voluntary – Menses-related most common – Other reasons  Cleaning VR (2)  Showing VR to partner (1 )  Fear of VR causing damage (1)  Investigating discharge or smell (2)  Having an infection (2)  Checking VR was there (2)

12. RTI International Results 3: Adherence  147 women provided data at each follow-up visit during ring use period, 82% of whom reported being perfectly adherent.  At each visit interval, at least 94% of women reported to wear the ring for all or part of the days (minimum 12 hours) and were defined as “100% adherent”  Almost all participants (99%) were at least 80% adherent at each visit.

13. RTI International Predictors of Perfect Adherence: MLR AOR est95% CIp-value Demographic and Sexual Behavior Characteristic (Baseline) Married vs. not married0.690.18-2.600.58 High perceived risk of HIV vs. Same or lower than others5.220.53-51.550.16 Ever used male condom vs. Never1.060.14-7.870.95 Ever used vaginal products for menstruation0.220.05-0.890.03 Site Moshi (vs. Cape Town)8.591.00-73.380.05 Johannesburg (vs. Cape Town)6.231.21-32.170.03 Durban (vs. Cape Town)2.420.47-12.460.29 Study group A (IVR> no IVR) vs. B (no IVR> IVR)0.210.07-0.64<0.01 Sexual Behavior, Product Attitudes and Use (at Exit) Ever had concerns about IVR coming out vs. never0.770.23-2.610.68 Ever had concerns about losing IVR inside body vs. Never0.350.10-1.210.1 Ever experienced physical problems with IVR vs. Never0.420.06-3.090.4 Partner knew about study prior to start of IVR use vs. After IVR use initiated or never1.260.39-4.080.7

14. RTI International Results 4: Qualitative  Qualitative data described removals associated with ring disclosure and device presentation to male partners. – She showed me the ring and said I am returning this ring. I asked her what is it for, and she said that was having it all the days even when having sex. I was so surprised, as I knew nothing at all. (Male partner, Moshi site)  Many women were concerned that the VR might be spontaneously expelled from their vagina, especially during sex – there are some days you will having sex with your partner and he might touch something strange…he will then ask you what is inside…you might end up being beaten. Until you show him what is inside (Female participant, Moshi site)

15. RTI International Results 4: Qualitative  Only one actual expulsion described in FGD – That morning when I went to the toilet it was too much [(menstrual) blood that came out and I was scared…Then I went to the clinic to tell them the ring might have come out because I didn’t feel it anymore. …when they checked me they found that the ring is out, then inserted another ring. (Female participant, Johannesburg site)

16. RTI International Conclusions  Self-reported adherence of placebo ring use for 12 weeks was very high.  Reasons for ring removal included menses-related and partner-related issues that could be addressed pre- emptively through counseling and product use instructions.  Trial designs with no product/condom-only run-in periods may select for more adherent study participants

17. RTI International More information See Also Poster# TUPE367 (011 Acceptability Poster, van der Straten et al.) For More information:  emontgomery@rti.org  Cynthia Woodsong cwoodsong@ipmglobal.org.za