A study was conducted in South Africa and Tanzania to assess the safety and acceptability of silicone elastomer vaginal rings as a potential method for delivering HIV microbicides. 169 women participated, with 85% completing the study. The vaginal ring was found to be safe and well tolerated, with vaginal candidiasis being the most common adverse event. While 10% reported the ring being expelled and 11% removed it, mostly related to menstruation, 82% reported no removals and 99% reported wearing it over 80% of the time. Male partners did not report feeling the ring impacting sexual pleasure. 95% found the ring comfortable and all women said they would use it if it prevented HIV. Rem

1. Annalene Nel1, Katherine Young1, Joseph Romano1, Cynthia Woodsong1, Elizabeth Montgomery2, Lungwani GileardMuungo, Masenga , Helen Rees4 , Linda-Gail
Bekker
5
, Shay Ganesh
6
1International Partnership for Microbicides, Silver Spring, MD, USA; 2Research Triangle Institute, San Francisco, CA, USA; 3Kilimanjaro Christian Medical Centre, Moshi, Tanzania; 4Reproductive Health and HIV Research Unit, Johannesburg, South Africa; 5Desmond
Tutu HIV Foundation, Cape Town, South Africa; 6Medical Research Council, Durban, South Africa
Safety & Acceptability of Silicone Elastomer Vaginal Rings as Potential Microbicide
Delivery Method in African Women
Abstract
Background: Vaginal rings are a long-acting dosage form in development for delivery of
HIV microbicides. Rings have been marketed in the US and Europe since the mid 1990s
for menopausal symptoms and since 2002 for contraception; however, African women, a
target population for HIV microbicides, have limited experience with vaginal rings.
Methods: A crossover, safety and acceptability study was conducted in healthy, sexually
active women at 3 research centers in South Africa and 1 in Tanzania. Women were
randomized 1:1 to a placebo vaginal ring for 12 weeks, followed by a 12-week no
treatment observation period, or vice versa. Safety was assessed by colposcopy,
adverse events, and laboratory assessments. Ring acceptability and adherence were
assessed by questionnaires.
Results: Of 169 women, 85% completed the study. Ring expulsions and removals were
reported by 10% and 11% of participants, respectively. The most common reason for
both expulsion and removal was menses related. In most cases (64%), the ring was
washed and re-inserted. Eighty-two percent of participants reported no ring removals for
the duration of the trial, and 99% of women reported wearing the ring for at least 80% of
the time. Male partner interviews indicated that men did not feel the ring during
intercourse, that it did not impact their sexual pleasure, and that they did not suffer any
side effects from the rings. Ninety-five percent of women found the ring to be very
comfortable. Vaginal candidiasis was the most common adverse event, occurring in 11%
of women during each period. Vaginal discharge (2%), vaginal odor (2%), and bacterial
vaginitis (2%) were assessed as possibly or probably related to the ring, and occurred
with similar frequency in the observation period. One SAE of appendicitis was assessed
as probably not related to the ring. Thirty-four percent of participants had STIs at
screening, and 12% had STIs at the crossover and final study visits. Three participants
(2%) tested HIV positive during the study, two at the crossover visit and one at the final
visit. All questionnaire responders were willing to use the vaginal ring if shown to be
effective for HIV prevention.
Conclusions: The vaginal ring was safe and well tolerated for 12 weeks in African
women. Participant removal of the ring for menses and cleaning indicates a need for
enhanced adherence counseling. All study participants found the ring acceptable and
would use it if shown to prevent HIV infection.
Figure 2. Flowchart of Study Events
Group A used the placebo ring for 12 weeks followed by a 12-week safety observation period. Group B was
observed for safety for 12 weeks followed by a 12-week period of placebo ring use. Participants with genital
symptoms or abnormal colposcopy findings at the crossover visit were to return to the research center 2 weeks
later to confirm resolution before participation in the second half of the study. Safety was assessed by pelvic
examinations, colposcopy, and monitoring of adverse events at the time points indicated. STI testing (bacterial
vaginosis, trichomonas gonorrhea, and chlamydia) and HIV rapid testing were done at the indicated time points.
A=Group A; B=Group B; AB=Groups A and B
Study Design
• Healthy, sexually active women aged 18-35 years
• 3 sites in South Africa, 1 site in Tanzania
• Participants randomized to 3 months of ring use and 3 months of observation (no product use) in a
crossover design
• Safety assessed by pelvic/speculum examination, colposcopy, and adverse event
monitoring
• Acceptability and adherence questionnaires administered at 5 points during the study (Figure 2)
• Participant focus groups and male partner interviews conducted at end of study
Study Design
• Healthy, sexually active women aged 18-35 years
• 3 sites in South Africa, 1 site in Tanzania
• Participants randomized to 3 months of ring use and 3 months of observation (no product use) in a
crossover design
• Safety assessed by pelvic/speculum examination, colposcopy, and adverse event
monitoring
• Acceptability and adherence questionnaires administered at 5 points during the study (Figure 2)
• Participant focus groups and male partner interviews conducted at end of study
• Off-white, flexible
• Tin-catalyzed, silicone
elastomer matrix ring
• 56 mm outer diameter;
7.7 mm cross-sectional
diameter
• Intended to be used
monthly or longer
Figure 1. Placebo Vaginal Ring
Safety Results
• 144 of 169 women (85%) completed the study
• No ring-related SAEs were reported
• Vaginal candidiasis was the most common TEAE, and occurred in 11% of
women during each study period
• 4 women had TEAEs assessed as probably related to the ring: coital
bleeding, vaginal odor, genital discomfort, and vulvovaginal discomfort;
All were mild with 1-2 days duration
• 5 women had TEAEs that resulted in temporary or permanent ring removal:
genital pruritus, vaginal candidiasis (2), coital bleeding, cervical erythema,
abdominal tenderness/lower abdominal pain, and vaginal laceration;
All were mild or moderate in intensity
• 1 pelvic/colposcopy finding assessed as probably related to the ring:
superficial labial abrasion (<5 mm) at 6 weeks post ring insertion; moderate
intensity, resolved at 8 weeks
• 34% of women had STIs at screening; 12% had STIs at crossover and final visits
• 3 women (2%) tested HIV positive; 2 at crossover visit and 1 at final visit
Safety Results
• 144 of 169 women (85%) completed the study
• No ring-related SAEs were reported
• Vaginal candidiasis was the most common TEAE, and occurred in 11% of
women during each study period
• 4 women had TEAEs assessed as probably related to the ring: coital
bleeding, vaginal odor, genital discomfort, and vulvovaginal discomfort;
All were mild with 1-2 days duration
• 5 women had TEAEs that resulted in temporary or permanent ring removal:
genital pruritus, vaginal candidiasis (2), coital bleeding, cervical erythema,
abdominal tenderness/lower abdominal pain, and vaginal laceration;
All were mild or moderate in intensity
• 1 pelvic/colposcopy finding assessed as probably related to the ring:
superficial labial abrasion (<5 mm) at 6 weeks post ring insertion; moderate
intensity, resolved at 8 weeks
• 34% of women had STIs at screening; 12% had STIs at crossover and final visits
• 3 women (2%) tested HIV positive; 2 at crossover visit and 1 at final visit
Table 1. Participants with Adverse Events Probably
or Possibly Related to Vaginal Ring*
MedDRA Preferred Term
Number and Percentage
with Event
N=169
Ring Removed Because
of Event
N=169
Any possibly/probably related
event
19 (11.2) 0
Vaginal discharge 3 (1.8) 0
Vaginal odor 3 (1.8)** 0
Vaginitis bacterial 3 (1.8) 0
Abdominal pain lower 2 (1.2) 1 (0.6)
Cervix erythema 2 (1.2) 1 (0.6)
Vaginal candidiasis 2 (1.2) 0
Vulvovaginal discomfort 2 (1.2)** 0
Abdominal tenderness 1 (0.6) 1 (0.6)
Cervical discharge 1 (0.6) 0
Cervix hemorrhage uterine 1 (0.6) 0
Coital bleeding 1 (0.6)** 1 (0.6)
Genital discomfort 1 (0.6)** 0
Genital erythema 1 (0.6) 0
Gynecological chlamydia infection 1 (0.6) 0
Uterine pain 1 (0.6) 0
*All of these events occurred during the Intervention Period. The event of gynecological chlamydia
infection and one event of vaginitis bacterial were reported on the day that the ring was removed and
the participant crossed over to the Observation Period.
**One of these events was assessed as “probably related” to the ring. All other events in the table were
assessed as “possibly related” to the ring.
Adherence
• 10% of women reported ring expulsions; 11% reported ring removals
• Most common reason for expulsion/removal was “menses related”
• In 64% of cases, ring was washed and re-inserted
Adherence
• 10% of women reported ring expulsions; 11% reported ring removals
• Most common reason for expulsion/removal was “menses related”
• In 64% of cases, ring was washed and re-inserted
Acceptability
• All questionnaire responders (152/152) were willing to use the vaginal
ring if shown to be effective for HIV prevention
• 99% rarely felt the ring during daily activities
• 95% found the ring to be very comfortable
• 94% found ring insertion to be very easy; 92% found removal very
easy
• 47% reported their opinion of the ring improved after 3 months of use;
53% reported no change in their opinion
• Of the 19 male partners that were interviewed, only 2 (11%) reported
a negative impact of the ring on his sexual pleasure
• A few men reported feeling the ring during sex
Acceptability
• All questionnaire responders (152/152) were willing to use the vaginal
ring if shown to be effective for HIV prevention
• 99% rarely felt the ring during daily activities
• 95% found the ring to be very comfortable
• 94% found ring insertion to be very easy; 92% found removal very
easy
• 47% reported their opinion of the ring improved after 3 months of use;
53% reported no change in their opinion
• Of the 19 male partners that were interviewed, only 2 (11%) reported
a negative impact of the ring on his sexual pleasure
• A few men reported feeling the ring during sex
Conclusions
• Use of a silicone vaginal ring for 3 months
was safe and acceptable to African women
• Removal of the ring for menses and cleaning
indicates a need for enhanced adherence
counseling
• All participants reported that they would
use a vaginal ring for HIV protection in the
future if it is shown to be effective to prevent
HIV transmission
Conclusions
• Use of a silicone vaginal ring for 3 months
was safe and acceptable to African women
• Removal of the ring for menses and cleaning
indicates a need for enhanced adherence
counseling
• All participants reported that they would
use a vaginal ring for HIV protection in the
future if it is shown to be effective to prevent
HIV transmission
CROI 2011
Poster no: 1004
Boston
Feb 27-Mar 2, 2011
8401 Colesville Road, Suite 200
Silver Spring, MD, USA 20910
anel@ipmglobal.org.za
TEL: 301-608-2221
FAX: 301-608-2241
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