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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, ItalyJuly 18, 2011

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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

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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.

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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

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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

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Adherence Study Objectives

To measure adherence to ring use To quantify ring expulsions and removals and

to describe circumstances surrounding these events

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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)

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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.

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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

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Ring Removals

34 ring removals were reported by 28 participants (18%) Evenly attributed to voluntary and involuntary circumstances

Week 4 Week 8 Week 12 TOTALVoluntary 6 7 3 16 (47%)Involuntary 8 4 5 17 (50%)Unknown 0 1 0 1 (3%)TOTAL 14 12 8 34

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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)

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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.

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Predictors of Perfect Adherence: MLR    AOR

    est 95% CI p-value

Demographic and Sexual Behavior Characteristic (Baseline)

Married vs. not married 0.69 0.18-2.60 0.58

High perceived risk of HIV vs. Same or lower than others 5.22 0.53-51.55 0.16

Ever used male condom vs. Never 1.06 0.14-7.87 0.95

Ever used vaginal products for menstruation 0.22 0.05-0.89 0.03

Site

Moshi (vs. Cape Town) 8.59 1.00-73.38 0.05

Johannesburg (vs. Cape Town) 6.23 1.21-32.17 0.03

Durban (vs. Cape Town) 2.42 0.47-12.46 0.29

Study group A (IVR> no IVR) vs. B (no IVR> IVR) 0.21 0.07-0.64 <0.01

Sexual Behavior, Product Attitudes and Use (at Exit)

Ever had concerns about IVR coming out vs. never 0.77 0.23-2.61 0.68

Ever had concerns about losing IVR inside body vs. Never 0.35 0.10-1.21 0.1

Ever experienced physical problems with IVR vs. Never 0.42 0.06-3.09 0.4

 Partner knew about study prior to start of IVR use vs. After IVR use initiated or never 1.26 0.39-4.08 0.7

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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)

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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)

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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

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More information

See AlsoPoster# TUPE367(011 Acceptability Poster,

van der Straten et al.)

For More information: emontgomery@rti.org Cynthia Woodsongcwoodsong@ipmglobal.org.za