HIV-1 Incidence, Adherence to Ring Use and Safety in an

Open-label Trial of Dapivirine Vaginal Ring - DREAMA Nel1, N van Niekerk1, M Malherbe1, W Mans1, L Solai1, C Louw3, T Gwetu4, Z Mabude4, P Kotze5, S Kusemererwa6, K Gill7, R Moraba8, H Tempelman8, B Van Baelen9, L-G Bekker7, Z Rosenberg2

1International Partnership for Microbicides, South Africa, Paarl, 2International Partnership for Microbicides, United States of America, Silver Spring, 3Madibeng Centre for Research, South Africa, Brits,4MatCh Research Unit, South Africa, Edendale5Qhakaza Mbokodo Research Clinic, South Africa, Ladysmith, 6Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit on AIDS, Masaka, Uganda7Desmond Tutu HIV Foundation, South Africa, Fish Hoek, 8Ndlovu Research Consortium, South Africa, Elandsdoring, 9BVB Clin Consult BVBA, Belgium, Herent

Background:DREAM is an ongoing Phase IIIb, multi-center, open-label follow-on trial to The Ring Study, a Phase III trial of the monthly Dapivirine Vaginal Ring (25 mg), to evaluate

continued safety and adherence to ring use. All participants who had previously participated in The Ring Study and were HIV-negative, and not pregnant or breastfeeding at

screening for DREAM, were eligible for enrollment.

P19.48LB

Conclusion:The HIV-1 incidence rate is approximately 59% lower than the expected rate in the absence of Dapivirine Vaginal Ring use. The lack of a placebo arm

limits interpretation but increased efficacy can be expected due to observed higher adherence to ring use in DREAM than in Phase III. DREAM

demonstrates a similar safety profile of Dapivirine Vaginal Ring to that observed in Phase III.

Methods:1034 women who participated in The Ring Study were screened, and 941 were enrolled at 5 Research Centers

(RCs) in South Africa and 1 in Uganda. All enrolled participants use the monthly Dapivirine Vaginal Ring.

Monthly RC visits occur up to 3 months after enrolment, followed by quarterly visits for a study period of

approximately 12 months.

HIV testing and safety evaluations are conducted at each visit, and returned used rings are analyzed for

dapivirine residual levels. The observed HIV-1 incidence rate was compared descriptively to the rate expected

by bootstrap sampling, based on the placebo arm of The Ring Study, selecting 10 000 times for a subset of

women matched for research center, age, and presence of a curable sexually transmitted infection at enrolment.

A total of 1054.1 person-years of follow-up have been reported up to 30 April 2018. An expected 100 additional

person-years will be accrued until the planned completion of the trial by end 2018.

Results:• By 30 April 2018, 571 (61%) completed, 67 (7%) discontinued early and 302 (32%) participants were ongoing.

• The observed HIV-1 incidence rate is 1.61 per 100 person-years (95% CI: 0.94 to 2.58).o HIV-1 seroconversion occurred in 26 participants; 17 were infected while using Dapivirine Vaginal Ring.

o Although interpretation of the data is limited by the lack of a placebo arm, the rate is approximately 59%

lower than the expected rate (3.92 per 100 person-years; 95% CI: 2.99 to 4.93 based on bootstrap analysis)

in the absence of access to the Dapivirine Vaginal Ring.

• Dapivirine residual levels in used rings are consistently lower in DREAM compared to The Ring Study:o 96% of returned used rings had a residual level ≤ 23.5 mg, indicating some ring use during the month,

compared to 83% in The Ring Study.

o Overall, most of the participants self-reported adherence to ring use to be in the ≥ 90% category.

• DREAM results indicate a similar safety profile to that observed in the Phase III trials:o SAEs were reported for 20 (2.1%) participants; no SAE or AEs led to permanent discontinuation of ring use.

o Pregnancies occurred in 26 (2.8%) participants.

o Social harms were reported by 24 (2.6%) participants.

RESULTS SUMMARY Overall

n (%)

Number of women screened 1034

Number enrolled a 941 (91.0%)

Number of enrolled participants with:

HIV-1 seroconversion 26 (2.8%)

HIV-1 seroconversion on IP b 17 (1.8%)

Adverse events (AEs) 602 (64.0%)

Serious AEs 20 (2.1%)

AEs resulting in permanent IP discontinuation 0

Pregnancies 26 (2.8%)

Social harms 24 (2.6%)

HIV-1 SEROCONVERSION RATE Overall

n (%)

Number of participants in m-ITT population c 935

HIV-1 seroconversions on IP b 17 (1.8%)

Number of person-years (PY) 1054.14

Seroconversion incidence rate (per 100 PY) 1.61

95% confidence interval (per 100 PY) 0.94 to 2.58

IP = investigational product, Dapivirine Vaginal Ring; n = number of participants with observation;SAE = Serious Adverse Event; AE = Adverse Eventa Percentage calculation based on total number of participants screened.b HIV-1 infected while using Dapivirine Vaginal Ring, based on reverse sequential HIV RNA PCR testing. Confirmation of HIV-1 infection on

IP was received for 2 additional participants after the data cut-off date. Of the remaining 7 HIV-1 seroconverters, 3 were already HIVinfected at enrolment, before commencing IP use; 3 were infected after last product use; and 1 participant discontinued ring use for 5months before seroconverting, as she was not planning on continuing in the trial.

c Includes all enrolled participants who were HIV-negative at enrollment.

Also see Poster Abstract Presentation P12.02

HIVR4P2018Madrid, Spain

21 – 25 October 2018

IPM’s work is made possible through generous support from the Ministry of Foreign Affairs of Denmark, Flanders Department of Foreign Affairs, Irish Aid, German Federal Ministry of Education and Research (BMBF) through the KfW Development Bank, the Ministry of Foreign Affairs of the Netherlands, the

United Kingdom Department for International Development (DFID), the American people through the United States Agency for International Development (USAID) in partnership with the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR), and the Bill & Melinda Gates Foundation.