PrEP for HIV prevention. Pep Coll AIDS Research Institute-IrsiCaixa Fight AIDS Foundation BCN Checkpoint

Transcription

1 PrEP for HIV prevention Pep Coll AIDS Research Institute-IrsiCaixa Fight AIDS Foundation BCN Checkpoint

2 DISCLOSURES I have received a research grant from Gilead Sciences awarded to my institution I have participated in Advisory Boards of Merck, Gilead and ViiV Healthcare I am a Principal Investigator of the DISCOVER study

3 AGENDA PrEP works! Always? Do we have to worry about safety and potential collateral damages? Is PrEP for everybody? If I want PrEP, how can I get it? What are the challenges?

4 Prevention based on ARV has become a cornerstone of HIV prevention Treatment as Prevention Post-Exposure Prophylaxis Pre-Exposure Prophylaxis (PrEP)

5 Estimated new HIV infections are decreasing globally, but increasing in the WHO European Region Global WHO European Region Source: ECDC/WHO (2016). HIV/AIDS Surveillance in Europe, UNAIDS/WHO global estimates.

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9 16 new HIV transmissions: 2 in active arm (incidence 0.94 per 100 PY) 14 in placebo group (incidence 6.6 per 100 PY) 86% reduction in N=414, randomized 1:1 13 months follow-up HIV incidence NNT for one year to prevent an infection = 18

10 HIV Incidence (mitt Analysis) On Demand PrEP Follow-Up Pts-years HIV Incidence per 100 Pts-years (95% CI) Placebo * ( ) TDF/FTC (double-blind) ( ) TDF/FTC (open-label) ( ) *Incidence: 9.17 in Paris (and 2.45 in other cities) 97% incidence reduction vs. placebo Molina et al AIDS 2016, July 20, Durban, South Africa

11 What about in real world? Kaiser Permanente Northern California on PrEP (most MSM) July 2012-February 2017 NO NEW HIV INFECTIONS

12 Does PrEP always work? 6 seroconversions reported so far 21 year-old Latino MSM Seroconversion at month 13 Good adherence (plasma, DBS and segmental hair analysis) Mutation M184V (transmission confirmed)

13 1 seroconversion in AMPrEP study Good adherence No drug resistance mutations But Multiples sex partners Recent rectal STI And

14 ChemSex Methamphetamine use is associated with increased local mucosal inflammatory cytokine production

15 Around people on PrEP Individuals taking PrEP and health care providers should be aware that PrEP failure is very rare, but not impossible, even with consistent adherence

16 Is PrEP safe? Study name Target Drug / Dosing Toxicity iprex (n=2499) HSH TDF/FTC QD vs placebo Nausea Weight decreased BMD ~1% US-MSM Safety (n=400) HSH TDF vs Placebo Back pain BMD ~1% TDF2 (n=1219) HTS men & women TDF/FTC QD vs placebo Nausea, vomiting, dizziness (1st month) Bangkok Tenofovir Study (n=2413) IVDU TDF Nausea, vomiting (1 st 2 months) Ipergay ANRS (n=414) HSH On-demand TDF/FTC Nausea, vomiting (1 st 2 months)

17 What about the renal toxicity? IPrEX OLE 1 Creatinine Clearance (CC) 2.5% (18 months) PrEP Demo Project 2 CC 2.8% (12 months) Kaiser Permanente 3 0.6% interruptions Risk factors: age, baseline CC, diabetes Infrequent if baseline CC > 90 ml/min 1. Gandhi et al. Abstract 866. CROI Liu AY et al. Abstract 867. CROI Volk JE et al.clin Infect Dis 2015

18 Reversible? Bangkok Tenofovir Study CC back to normal (within median 20 months) Martin M et al. Clin Infect Dis 2014

19 But what about sex?

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21 STIs 60 p= p=0.44 p=0.08 p=0.32 p=0.44 Immediate Deferred

22 MSM reported decreased condom use during receptive anal intercourse with HIV seropositive partners in the first year after initiating PrEP

23 What about Hepatitis C? 376 MSM and TGW HCV prevalence: 4.8% HCV incidence: 1/100 py Re-infection rate: 25.5/100 py 75% reported ChemSex

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26 What about drug resistance? Most of drug resistances would be due to starting PrEP in individuals already infected Very important to rule out an HIV infection before starting PrEP 4 th generation tests and/or PCR

27 PrEP for whom?

28 Guidelines on PrEP National Guidelines

29 WHO guidelines on PrEP (2015) Oral PrEP should be offered as an additional prevention choice for people at substantial risk of HIV infection as part of combination HIV prevention approaches Substantial risk of HIV infection is provisionally defined as HIV incidence greater than 3 per 100 person years

30 EACS guidelines PrEP can be used in adults at high-risk of acquiring HIV infection Recommended in HIV-negative MSM and transgender individuals who are inconsistent in their use of condoms with casual partners or with HIV-positive partners who are not on treatment May be considered in HIV-negative heterosexual women and men who are inconsistent in their use of condoms and likely to have HIV positive partners who are not on treatment

31 If I want PrEP, where can I get it?

32 Status of formal PrEP implementation in Europe (as of 26 October 2017) ECDC. Evidence brief: Pre-exposure prophylaxis for HIV prevention in Europe. Stockholm: ECDC; (updated)

33 Available through the National Health System in: France Belgium a small co-pay fee is required (also in France) Norway Scotland Portugal Israel

34 Demonstration or implementation studies Netherlands England Wales

35 Demonstration or implementation studies Spain Feasibility study Sponsored by: Spanish Ministry of Health PrEP-ara Sponsored by: Health Department of Catalonia

36 DISCOVER: FTC/TDF vs. FTC/TAF Clinical Trials HPTN 083: LA CABOTEGRAVIR (MSM and transgender women) HPTN084: LA CABOTEGRAVIR (women)

37 Informal PrEP

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39 Germany 50-Euro-PrEP-program Netherlands Italy Source:

40 BCN Checkpoint was the first community based organization implementing HIV rapid test in Spain BCN PrEP Point (created in November 2017) is the first community centre providing PrEP in Spain 700 MSM and transgender women on PrEP

41 Challenges PrEP being approved and available within National Health Services Close partnership with the community and strong political support Increase PrEP awareness among health professionals and people at risk (MSM, transgender and heterosexual migrants) Define appropriate models of care and access points (hospitals, sexual health clinics, primary care, community-based organizations) How best to integrate PrEP into existing services

42 Challenges Monitor and evaluate PrEP implementation Development of new formulas (Long Acting drugs, implants, neutralizing antibodies) Reduce cost of drugs for PrEP

43 What are we waiting for?

44 Acknowledgements Teymur Noori BCN Checkpoint team