10/05/2016. PrEP : from proof of concept to real life. E. CUA Nice university hospital

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1 PrEP : from proof of concept to real life E. CUA Nice university hospital 1

2 Disclosures Received honoraria and acted as consultant : Merck, Gilead, ViiV Co-investigator: Merck, Gilead, ViiV and BMS phase 3 studies 2

3 3

4 4

5 The burden of the HIV epidemic in MSM : 5

6 Women living with HIV : 6

7 ARV Coverage : 7

8 The cascades : 8

9 Birth of PrEP : 9

10 10

11 J. Gerardo Garcia-Lerma,

12 12

13 FTC-TP TFV- DP Kristine B.Patterson, Sci Transl Med

14 TDF-FTC 24H before and 2H after Vaginal challenge, once week during 18 W Pigtail macaques Jessica Radzio,

15 Urvi M.Parikh. Journal of Virology, Oct

16 Ring strategy : Smith JM, Proc Natl Acad

17 The clinical trials : 17

18 18

19 iprex study : 19

20 Partners PrEP Study: 20

21 TDF2 Study Group : 21

22 FEM-PrEP and VOICE : VOICE FEM PrEP 22

23 ASPIRE Study 23

24 Bangkok Tenofovir Group : 24

25 The sister studies 25

26 PROUD, n= 544 IPERGAY, n = 414 Median Age White 80 % 90 % University degree 60 % 70 % STI 63 % in the past 12 months 30 % at screening Chemsex in the past 3month 45 % 43 % 10 years older than the iprex participants White and well educated High rates of STI at baseline Probably at greater risk of acquiring HIV than the overall MSM population 26

27 5 infections 27

28 28

29 Median number of pills /month : 15 29

30 30

31 Drug concentations associated with HIV protection : 31

32 A TFV-DP of 16 fmol per M is associated with a 90% reduction in HIV acquisition (CI: 3 to 38). 32

33 33

34 Simple dose PK and PD of Truvada in blood, saliva and rectal tissues A Ipergay sub-study, 12 participants, unique dose of 2 pills in morning time Blood and saliva : 0 H, 0.5 H, 1 H, 2 H, 4 H, 8 H, 24 H TFV-DP and FTC-TP in PBMC : 2 H and 24 H post dosing TFV and FTC in rectal biopsies : one before and one post dosing Controls 7 HIV-infected patients on stable TDF/FTC Molina JM, in press 34

35 Results : 2 H 24 H Median TFV-DP 12,2 16,7 % > 16 fmol/10 6 cells 33 % 58 % Median FTC-TP 2,8 2 Ration Saliva / plasma concentration : 17 % for FTC and 2 % for TFV 35

36 Drug concentrations in tissues and compartiments : Ration Saliva / plasma concentration : 17 % for FTC and 2 % for TFV 36

37 Tolerability : 37

38 Bone mineral density in men : 38

39 BMD in Women : 39

40 4640 subjects randomized and followed on either daily TDF, or daily TDF-FTC or placebo from the partner PrEP study in Africa Median follow-up was 18 months The proportion of persons who developed a confirmed > egfr decline more than 25 % from baseline by 12 and 24 months was 1.3 and 1.8 for TDF and 1.2 and 2.5 for TDF-FTC And these frequencies were not statistically different compared to placebo 40

41 Mean egfr evolution 10/05/ Iprex-OLE : % 0 Relation between the egfr evolution since inclusion and TFV hair concentration -1 p = 0, doses TDF/week 4 doses TDF/week 7 doses TDF/week IQR bas 2 ème IQR 3 ème IQR IQR haut Capillar concentrations (IQR) Gandhi M, CROI 2016, Abs

42 % Probability of egfr reaching < 70 ml/min, according to le TFV concentration and age ,6 % ,5 % doses TDF/W % ,7 % 4 doses TDF/W 7 doses TDF/W > 50 years years % ,6 % ,5 % < 40 years ,6 % 0 IQR bas 2 ème IQR 3 ème IQR IQR haut Capillars concentration in IQR Gandhi M, CROI 2016, Abs

43 Drug resistance and PrEP Partners PrEP : 121 infections, 26 with plasma drugs levels indicating PrEP use during or after HIV aquisition 5 had virus with resistance mutation ( more frequent in the TDF-FTC arm) 3 had unrecognised acute infection at randomization iprex : Of the 48 on-study infections randomized ontdf-ftc none showed resistance mutation (8 with detectable drug level) Minor variant in 2 participants but at low proportion : < 1% FTC resistant mutation in 2 of 2 infected at randomization in the TDF-FTC group Proud and Ipergay : 1/ 5 : «the english patient» unrecognised acute infection at randomization A LEHMAN, JID 2015 T LIEGLER, JID

44 NICE is PrEP-ared! inhabitants French second biggest airport HIV cohort : 2800 patients 44

45 FRANCE 60% 45

46 + 20 % new infection in 2014 / 24 % < 30 years old 46

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48 December 1st 2015 : PrEP is authorized by the Health Minister Covered by health national insurance from January 2016 One week later, our program started in Nice 48

49 Since January 2016 : Mean age: 40 Years STI : 50 % 57 voluntary men 52 inclusions in the PrEP program Chems : 63 % + 41 in Ipergay On demand : 81 % 49

50 Kaiser Permanente San Francisco 32 month period 657 PrEP initiators Mean age : person years of use PrEP After 12 month 50 % of PrEP users were diagnosed with one or more STI No HIV infection Volk JE, CID

51 CONCLUSION 51