ASPIRE Overview Where we are today

Transcription

1 ASPIRE Overview Where we are today Flavia Matovu Kiweewa, MBChB, Msc. Makerere University-Johns Hopkins University (MU-JHU) Research Collaboration Beyond Phase III: Seeking civil society perspectives on next steps with the dapivirine ring for HIV prevention in women 16 July 2014, Kampala

2 Overview o ASPIRE at a glance, timeline and sites o Study design o Primary and secondary objectives o Summary

3 ASPIRE at a Glance o Phase III trial evaluating safety and effectiveness of the dapivirine ring when worn for 4 weeks at a time o Being conducted at trial sites affiliated with the Microbicide Trials Network (MTN) o MTN and ASPIRE are both funded by the U.S. National Institutes of Health o IPM is the regulatory sponsor and providing the rings for the study o ASPIRE is being led by: n Protocol Chair - Jared Baeten (University of Washington/USA) n Protocol Co-Chair - Thesla Palanee (Wits Reproductive Health and HIV Institute/SA)

4 ASPIRE Timeline o Started August 2012 o Completed enrollment June 13, 2014 o Expect to complete follow-up of all participants June/July 2015 o Results expected late 2015 or early 2016

5 ASPIRE has enrolled 2,629 women at 15 sites in 4 countries Blantyre Lilongwe Malawi (272 women) Cape Town Durban (7 sites) Johannesburg South Africa (1,426 women) Kampala Uganda (253 women) Harare/Chitungwiza (3 sites) Zimbabwe (678 women)

6 ASPIRE in Uganda Makerere University-Johns Hopkins University (MU-JHU) Research Collaboration Kampala

7 ASPIRE Study Design o Women randomly assigned to use a ring with dapivirine or one with no active drug both look alike o Blinded - neither participant nor study staff knows which ring o All women use the ring for at least 1 year, replacing it every month o All receive HIV prevention package

8 Study Objectives Primary Objectives o Is the ring effective in preventing HIV? o Is the ring safe to use? Secondary Objectives o Will women find it acceptable to use? o Will women actually use the ring, and use it properly? o If a woman becomes infected, will drug resistance be a problem?

9 How will we know it s effective? n At the end of the study we will compare the number of HIV infections that occurred among women in the group using the dapivirine ring with the number of HIV infections in the group using a placebo ring n ASPIRE is designed to see 60% fewer infections compared to the placebo n A reduction that s less than 60% could still be statistically significant and considered a success

10 How will we know it s safe? o o o Participants health is assessed at each monthly study visit We will compare the number, frequency and type of side effects/problems between the two groups Safety data are reviewed at multiple levels: the site, the study as a whole, and by the independent Data and Safety Monitoring Board (DSMB)

11 How will we know if she likes the ring and is using it? o Participants are asked questions by staff and also answer questions using ACASI (Audio Computer-Assisted Self-Interview) o Looking to know: n Does she have discomfort? n Does she notice the ring during daily activity or sex? n Is her partner aware of the ring during sex? n Did she take the ring out or did it come out on its own? n If so, why? And how long was it out?

12 Adherence is Important o Even the most effective products don t work if they are not used o Adherence is being monitored by: n Self-report n Measuring dapivirine levels in blood samples and in the used rings (while maintaining the blinding of the trial)

13 Adherence Action! Sites are using creative approaches to engage participants and talk about the importance of adherence

14 Is drug resistance a concern? o Resistance is only possible in someone who has HIV, and women who enroll in this trial are HIV negative o Women are tested monthly for HIV and if a woman tests positive, product is stopped immediately to reduce risk for resistance o Resistance has been rare in prevention trials involving tenofovir-based products o Women who acquire HIV are linked to HIV care and closely monitored to understand possible resistance to dapivirine that could possibly affect response to treatment with other NNRTIs, including nevirapine and efavirenz

15 Summary o ASPIRE is a Phase III trial evaluating safety and effectiveness of the dapivirine ring when worn for 4 weeks at a time n Being conducted in parallel with The Ring Study o Have enrolled 2,629 women at 15 sites in Malawi, South Africa, Uganda and Zimbabwe o Expect to complete follow-up of all participants June/ July 2015 o Results expected late 2015 or early 2016

16 Thank you ASPIRE and the MTN are funded by the U.S. National Institutes of Health grants UM1AI068633, UM1AI068615, UM1AI106707