1. Getting the FACTS Right!
Update & Scenario Planning for FACTS001 Trial
Manju Chatani-Gada & Kay Marshall
February 2015

2. (Thanks to FACTS001 team for the update slides)
FACTS 001 UPDATE
(Thanks to FACTS001 team for the update slides)

3. CAPRISA 004 results in 2010
Ground-breaking South African study was first to show microbicide could work to prevent HIV
Study showed tenofovir gel reduced the risk of vaginally transmitted HIV by 39% when used before and after sex (BAT24)
Also demonstrated a reduction in the risk of Herpes Simplex Virus 2 (HSV2) by 51%.

4. Why do a confirmatory study?
Build safety data required for licensure
Safety
CAPRISA 004 Results showed 39% effectiveness
Need to better understand level of effectiveness the gel can provide
HIV Protection
CAPRISA 004 only included 899 women in KZN
Need to test product in more women in diverse settings
Generalizability
Need to confirm and expand data on level of effectiveness of tenofovir gel to prevent HSV-2
HSV-2
**Note that CAPRISA 004 plus VOICE combined do not provide the required 3000 women years of safety data that the FDA wants. MTN plans to fill that gap with data from CHOICE, but FACTS 001 ALSO will provide that critical data.

5. FACTS 001 Overview & Timelines
Large-scale, double-blinded placebo-controlled
Aimed at confirming and expanding the CAPRISA 004 findings for licensure
Enrolment started Oct 2011
2,059 healthy, HIV-negative women,18 to 30 years, enrolled at 9 sites
Participant follow-up concluded in August 2014
Results expected at CROI 2015
Positive results could lead to licensure of first vaginal microbicide and expand women’s options for HIV prevention methods
(Slide Adapted by AVAC – Feb 2015)

6. WHEN USED BEFORE AND AFTER SEX.
Purpose of the study
Is 1% tenofovir gel:
safe for women,
effective for preventing HIV infection,
effective for preventing genital herpes
WHEN USED BEFORE AND AFTER SEX.

7. Who could participate in FACTS 001?
HIV-uninfected women
Sexually-active
Aged 18 to 30 years
Agreed to be on hormonal contraceptive
Women WERE still allowed to enroll if they:
had genital herpes
had Hepatitis B
were breastfeeding

9. “Active” gel with tenofovir Placebo gel without tenofovir
How the study worked
After recruitment, all participants were randomly placed in 1 of 2 groups OR
“Active” gel with tenofovir
Placebo gel without tenofovir

10. They were instructed to use study gel before and after sex…
asap
12 hours
12 hours
A woman must insert the gel vaginally within 12 hours before having sex (this could even be in the few minutes before sex) and then another gel must be inserted as soon as possible and within 12 hours after sex. The sooner she inserts it after sex, the better.
FACTS 001: Community Presentation V June 2012

11. They had monthly follow up visits
Monthly follow up visit procedures included:
Clinical
HIV counselling and testing
STI testing and treatment
Pregnancy testing
Physical examination
Participant support
Risk reduction counselling and provision of condoms
Motivational interviews to support participants to use gel
FACTS Clubs (social and support groups)

12. What happens between now and when the results are announced?
(*AVAC Note: This is what they said in August 2014 at community dialogues)
What happens between now and when the results are announced?
Participants have finished their study visits as required by the protocol.
The study team is now preparing the data to be analysed (by checking that everything was filled in correctly and completely) that has been collected over the past 3 years.
Once the data is analysed, final results will be released (planned for early 2015).
Each participant has made valuable contributions to this study.

13. And now?
FACTS001 results will be announced at the 2015 Conference for Retroviruses and Opportunistic Infections (CROI) on 24 February in Seattle
Trial participants, other stakeholders, media will also hear the results around that time
But the first set of results will only be top-level, still more analysis to do… (won’t have all the answers)

14. And then - if it works? And if it works – what about other countries?
The study team, sponsor and other stakeholders are planning for possible positive results of FACTS 001
Open-Label Extension study –will invite all eligible former FACTS participants to join OLE and receive active tenofovir gel
Additional research to facilitate product licensure (e.g. Adolescent safety study)
Licensure preparations
Social marketing research
Manufacturing, packaging, costing and distribution
Demonstration projects and roll-out plans
And if it works – what about other countries?

15. Consider…
If you were to asked to speak to an audience of other advocates about FACTS study, what are the three most important messages you would want to convey?
And what would you say to your aunty – about why this South African study is important for you to follow?

16. 3 Key Points to remember:
FACTS001 is meant to confirm previous positive results about tenofovir gel
Even if the results show it works – the gel will not be available immediately: there are several different processes from research to rollout
Even if the results do not show it works (well) – there is other ongoing microbicide research; the research will still teach us many important things (That’s how scientific enquiry goes!)

17. Considering the results…
What will the results be?
What will be their implications?
What could they mean for the HIV field?
Let’s consider the possible scenarios… but before that….

18. News: Final VOICE study data
Final study results published Feb 5
Bottom line remains the same: 3 products tested were safe but overall not effective in preventing HIV
Additional analysis (blood drug levels) shows 3 months into the trial, majority of participants not using any product
But among women who did use tfv gel (had drug in blood at 3 mo. visit) – a 66% reduction in HIV risk (statistically significant, BUT small group; not primary analysis)
Encouraging, but we cannot infer from this that FACTS will work

19. Consider and plan How will you respond? What will the media say?
What would you like the media to say?
How do you want policy-makers to act?
How can you advocate or influence messages and follow-up?

20. FACTS 001 Possible scenarios
It works (e.g., 50% effective)
It doesn’t work (e.g. “flat” results)
It’s complicated (e.g., low efficacy, low adherence, not immediately clear how/if it will move forward)

21. Back to the task at hand: Why we need to anticipate results & messages?

22. Top line messages -- It works
Amazing results – exciting moment for women in fight to end HIV
Shows us women will use products
Confirms CAPRISA004
Cannot delay –donors, researchers, advocates, others must work to move forward for licensure and access
Need more research for more, even better options
Grateful for women in trial, researchers, communities

23. Top line messages -- It doesn’t work
Disappointed not to have gotten the result we all hoped for…
…but need to find additional HIV prevention options for women as important as ever
Must continue to support other options being tested and additional research
Grateful for women in trial, researchers, communities

24. Top line messages -- It’s complicated
Could be additional proof for new option for women, but need more information to illuminate way forward
Must be stringently reviewed by regulators to determine way forward
Researchers, advocates, others must engage with regulators and policymakers as decisions being made
At same time, must continue to support other options being tested and additional research
Grateful for women in trial, researchers, communities

25. Consider and plan How will you respond? What will the media say?
What would you like the media to say?
How do you want policy-makers to act?
How can you advocate or influence messages and follow-up?

26. “After climbing a great hill, one only finds that there are many more hills to climb.”
Nelson Mandela