Andrew Grulich, HIV Epidemiology and Prevention Program, Kirby Institute, UNSW

1. BBVSS ETAG on revised HIV prevention targets for the proposed National HIV Strategy Update: Reportback to BBVSS Andrew Grulich, HIV Epidemiology and Prevention Program, Kirby Institute, UNSW

2. ETAG on revised HIV prevention targets Membership • Andrew Grulich, David Wilson, Kirby Institute • Darryl O’Donnell, NSW Health • Jo Watson, NAPWA • John de Wit, NCHSR • Christine Selvey, Chair, National BBV&STI surveillance subcommittee of CDNA • Bill Whittaker

3. ETAG on revised HIV prevention targets Terms of reference • propose and provide expert advice on HIV prevention targets appropriate to the Australian context, derived from the UN Declaration and noting the advice of Bill Whittaker; • advise on the relative contribution of different actions to achieving the targets, including testing, treatment and PrEP (within a culture of continued condom promotion), based on modelling and other evidence; • act as an advisory mechanism to the BBVSS National HIV Strategy Update Working group on the science and Australian data underpinning current discussions.

4. ETAG on revised HIV prevention targets Today’s report back • Science • Actions • Targets others have proposed • Modeling (David Wilson) • Socio-behavioural research • Monitoring • How high should we aim?

5. Science Recent findings in HIV prevention research findings represent a prevention revolution, the prevention equivalent of the 1996 “protease moment”

6. New resultsPre-exposure prophylaxis

7. The iPREX study: PrEP in homosexual men 44% reduction • HIV negative MSM in South/North America, Thailand • Randomized TDF/FTC vs Placebo • No-one with detectable drug levels became HIV infected • Is it really 95% effective? Probably yes • Should be answered by open-label extension phase, due to report end 2012 73% reduction

8. RCTs of PREP in heterosexuals • PARTNERS PrEP (TDF, TDF/FTC; 4,758 heterosexual couples, Africa) • Reduction in HIV risk was: • TDF 67% • TDF/FTC 75% • 90% reduction in risk if drug detectable (CROI 2012) • CDC TDF2 trial (TDF/FTC, 1219 heterosexual men and women in Botswana) • 63% reduction in risk • FEMPREP (TDF/FTC, 1951 African women) • RR 0.94, not sig, trial stopped in April 2011. Adherence 30%

9. What is happening now with PrEP? • Gilead has filed for a “prevention indication” for Truvada for MSM with the US FDA • May be available soon @ $10,000 pa • FDA ruling by mid 2012 • ?In Australia • On cost-effectiveness grounds, PBAC would offer a substantially smaller subsidy than the price for HIV therapy • ?Other funding mechanisms • No roll out or demonstration projects are currently planned • Why not?

10. Treatment as prevention

11. HPTN 052: Does early HIV treatment reduce transmission? A RCT in HIV serodiscordant heterosexual couples Cohen, MS et al, 2011

12. A 96% reduction in HIV transmission risk 96% reduction Cohen, MS et al, 2011

13. Treatment as prevention in homosexual men • A RCT of treatment as prevention is no longer possible • Observational studies of treatment and transmission • PARTNER study • Europe, recruiting currently • Opposites Attract • NHMRC funded 2011-2015, recruiting in Australia from April 2012 • These studies will not report back for several years

14. The evidence revolution has happened: what action is required?

15. Required elements of the prevention revolution • Increase HIV testing in people at risk • Earlier diagnosis of HIV • Increased proportion of those diagnosed with HIV on treatment • Decreased viral load in the community • Decreased new HIV transmissions

16. What might the new landscape look like? • Increased testing • Ramped up, “community-based” rapid testing; “One-stop” traditional testing; easier access to free testing • Average period between infection and diagnosis must be dramatically reduced • Increased treatment • A new type of prevention counselling/community education • Information giving about the likely reduction in transmissibility associated with treatment • Emerging evidence of therapeutic benefit at any stage of HIV • All PLWHIV should be given the choice option of starting treatment early • PrEP available for a small minority of very high risk HIV negative men

17. What needs to change? Change at every level is required…. • Policy • Leadership in embracing the new prevention tools • Clinical/laboratory • Clinical treatment guidelines, rapid test ramp up • Research • Observational studies of effectiveness at the population level • Community • Mobilisation and leadership • Education about viral load and transmission • Industry • Funding for demonstration projects, embracing of prevention goals of therapy

18. Targets

19. Australian national HIV strategy (2010-13)

20. Australian national HIV strategy (2010-13)

21. US National HIV strategy targets (2010)

22. San Francisco HIV prevention plan (2010)

23. European action plan for HIV/AIDS 2012-2015

24. European action plan for HIV/AIDS 2012-2015

25. European action plan for HIV/AIDS 2012-2015

26. UN Political declaration on HIV/AIDS

27. Whittaker paper

28. Modelling David Wilson and James Jannson

29. Sociobehavioural research John de Wit

30. Barriers and facilitators of HIV testing in gay men A substantial proportion of gay men have not recently tested or do not routinely test for HIV and STIs. • New knowledge is needed to understand and address barriers to (routinely) testing in MSM • The survey How much do you care? aimed at − Assessing frequency, recency and perceived patterns of testing for HIV and STIs among gay men (e.g. never tested; tested but no routine; routine testing) − Understanding complex individual, social and structural barriers and facilitators to ever, recently and routinely testing − Prioritizing barriers and facilitators of testing for HIV and/or STIs that need to be addressed by health promotion programs

31. Methods How much do you care? survey Online, quantitative self-report Conducted April - October 2011 Recruitment mostly via targeted ads on Facebook 190 (sets of) questions − Demographics − Sexual and risk practices − Testing practices and patterns − Barriers to and facilitators of testing 1274 male participants − Median age: 27 years − 94% identified as gay − 76% Anglo-Australian background − 95% NSW and ACT

32. Improving antiretroviral treatment (ART) initiation for people living with HIV in Australia: a realistic and viable approach (NHMRC Project Grant 2012-4) Aims (abridged): • Generate robust estimates of ART status of PLHIV (current use, past use, naïve) • Model potential population effects of increases in ART coverage on reducing HIV incidence • Identify key clinical, personal, social and structural barriers to ART uptake and reasons for non-use • Investigate main concerns and practices of S100 prescribers regarding ART initiation

33. Mixed-methods study, two parallel components • Utilisation of existing data • Literature and database review to generate estimate • Mathematical modelling of increased ART coverage • Collection of new data re barriers and concerns • Focus group discussions with NAPWA peer officers • Telephone interviews with ART-naïve PLHIV • Telephone interviews with ART prescribers • Online survey among ART-naïve PLHIV nationally

34. Monitoring

35. Monitoring- testing rates • Self-reported testing in periodic surveys • Men ever tested about 87-90%, slightly declining. • Tested in last 12 months 59-66% • Demonstrated to be an over-estimate

36. Monitoring-CD4 at diagnosis

37. Monitoring-CD4 at diagnosis

38. Monitoring- % of those diagnosed on treatment

39. Monitoring- % of those diagnosed on treatment Futures: around 80% on treatment

40. Monitoring- viral load AHOD Periodic surveys: % HIV+ men with detectable VL has declined from around 40% in the early 2000’s to around 20% now. Futures: 94% of those currently receiving ARV’s have undetectable VL.

41. Monitoring-HIV infections

42. Monitoring: what needs to change Three most important elements • CD4 at HIV diagnosis • Must increase very substantially to 600 or more • Median Viral load • No accurate systems currently in place • Likely a useful early measure of impact • Requires some work to design an efficient system • HIV diagnoses/newly acquired HIV • Should expect substantial increase in year 1 of such a strategy

43. How low should we aim?

44. How low should we aim: for debate A 50% reduction • Arguments for: • Modelling suggests it is ambitious but potentially achievable • Consistent with UN targets • Arguments against • Australia should be able to do better • Modelling doesn’t take into account all potential drivers

45. How low should we aim: for debate An 80% reduction in MSM (as in the Whittaker paper) • Arguments for: • Visionary • Australia should be able to do better than the global target • Modeling cannot take into account all the effects of community mobilisation • Arguments against • Australia has already gone a long way towards implementing treatment as prevention, and further decreases will be even more difficult than in places which have had poor prevention programs until now

46. How low should we aim: for debate What extra would we need to do to go lower? • A major focus on identification of primary infection to allow • Very early treatment • Community education and individual counselling about the high level of infectiousness in people with untreated primary infection • Reductions in risk behaviour