The Changing Landscape of Biomedical HIV Preven:on Research Mitzy Gafos

Transcription

1 The Changing Landscape of Biomedical HIV Preven:on Research Mitzy Gafos MRC Clinical Trials Unit at University College London 25 th April 2014

2 Behavioural Interven:ons abstain, be faithful Male condoms Female condoms PMTCT HIV Preven:on 2010 HIV tes:ng Needle exchange VMMC Post Exposure Prophylaxis STI treatment

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5 Oct 2009: RV144 HIV vaccine

6 Ongoing HIV Vaccine trials Since 1995 MRC CTU have co- ordinated 8 HIV vaccine trials hkp:// Phase Number enrolled Started Follow up completed V November 1995 February 1998 ICOX April 2002 August 2004 EV August 2003 October 2004 EV February 2005 July 2006 Mucovac November 2011 January 2013 EV03/ANRSvac20 1/2 147 August 2007 November 2009 Tamovac1 1/2 129 March 2010 Tamovac Support Imperial College London in the UKHVC & Cuthivac trials Over 30 other ongoing trials: hkp://data.avac.org/ongoingvaccinetrials.aspx

7 July 2010: Tenofovir microbicide

8 Ongoing vaginal microbicide trials FACTS 001: Tenofovir gel (BAT24) 8 sites in SA, enrolling 2060 women 18-30yrs IPM027 The Ring Study dapivirine monthly ring 7 sites in SA/Uganda, enrolling 1950 women 18-45yrs MTN 020 ASPIRE dapivirine monthly ring 15 sites in Malawi, SA, Uganda, Zim, enrolling 3476 women 18-45yrs Over a dozen other studies to support licensure: hkp://data.avac.org/ongoingmicrobicidetrials.aspx

9 Oct 2013: First rectal microbicide trial MTN017: Phase II trial Reduced glycerin formulacon of tenofovir gel Daily Before and aeer sex Truvada oral daily Enrolling 186 MSM/TSW in Peru, South Africa, Thailand and the United States

10 July 2011: Treatment as Prevencon

11 Ongoing TasP trials PopART/HPTN 071: 24 villages, 60,000 people in South Africa & Zambia SOC Test and ARV for all posicves Test- linked ARV for all CD4 <350 JHU USAID: 24 clusters, 12,000 people in Tanzania SOC Test- linked ARV for all CD4 <350 Botswana Combinacon Prevencon Project: 30 villages, 20,000 people SOC Test and ARV for all viral load above 10,000 ANRS Trial: 32 clusters, 40,000 people in South Africa SOC Test and ARV for all posicves

12 November 2010 Nov 2010: Pre- Exposure Prophylaxis Study Drug Popula:on Effect (95%CI) Detectable iprex Truvada G/MSM/TSW: Braz, Eca Peru SA Thai USA April 2011 FemPrEP Truvada Women: Kenya, SA, Tanz July 2011 July 2011 Partners PrEP Partners PrEP July 2011 CDC TDF2 Truvada Hetero Botswana November 2011 VOICE Tenofovir Women; Malawi, SA, Uganda, Zim March 2013 VOICE Truvada Women; Malawi, SA, Uganda, Zim June 2013 CDC Bangkok *Subsequent mathema:cal Truvada modelling Discordant based on drug levels Kenya, Uganda observed in iprex es:mate that Tenofovir daily Truvada Discordant use could reduce Kenya, Uganda the risk of HIV infec:on by as much as 99%. Tenofovir IDU Thailand 44% (15, 63) 0% 75% (55, 87) 67% (44, 81) 62% (22, 83) 0% 0% 49% (10, 72) 92% (40, 99) * 86% (57,95) 90% (56, 98) 78% 74% (17, 94)

13 Truvada demonstracon studies Approx. dozen in USA & dozen in E/S/W Africa, South America, Thailand, India and Australia All open- label without control groups For more details of PrEP demonstracon studies: hkp://data.avac.org/ongoingpreptrials.aspx UK conduccng only open label controlled trial of Truvada

14 Ongoing Alternacve PrEP trials IPERGAY (phase III) France, Canada, Germany Randomized to "on demand" (pre/post sex) Truvada versus placebo ADAPT (HPTN 067 ) (phase II) - SA, Thailand, US Randomized to daily, cme- driven (twice week/post), and event- driven (BAT24) dosing NEXT- PrEP (HPTN 069/ACTG 5305 ) (phase II) - USA Randomized to different combinacons: Maraviroc, M+ FTC, M+TFV, FTC+TFV HPTN 076 (Tibotec) & HPTN 077 (GSK) 3 month long accng slow release products

15 UK posi:on March 2011: BHIVA- BASHH posicon statement Need evidence for the value of PrEP in the UK Recommend that ad hoc prescribing of PrEP be avoided and PrEP be prescribed in the context of a clinical research study in order to collect UK specific informacon as quickly as possible. July 2011: applicacon for RCT randomising ~5,000 gay men to have access to Truvada as part of the package immediately or aeer 12m follow- up Dec 2011 rejected Nov 2012: started pilot study International Journal of STD & AIDS 2012; 23: 1-4

16 PROUD Pilot Study PRe- exposure Op:on for reducing HIV in the UK: an open- label randomisa:on to immediate or Deferred daily Truvada for HIV nega:ve gay men

17 PROUD Pilot 500 MSM repor:ng UAI last/next 90dy, 18+, Willing to take a pill Randomize HIV nega:ve MSM (exclude if on treatment for hepb/truvada contra- indicated) Truvada NOW and MI+ Truvada IN 12M and MI+ Follow 3 monthly for up to 24 months Main endpoints: recruitment and reten:on

18 Aims of Pilot Feasibility of larger clinical trial Level of interest in PrEP in clinic populacons (R&R) Acceptability of randomisacon Characterisccs of men who take up offer of PrEP Risk behaviour, impact of PrEP on risk micgacon/ compensacon (self- report, STIs) Adherence behaviour over cme (self- report, pill count, subset of PK, MEMS Cap) Facilitators and barriers related to adhering to a daily pill and related to risk behaviour (risk- adherence matrix IDIs)

19 PROUD Cohort Based on 470 baseline CRFs 35 median age 79% white; 58% UK born 60% university educated, 82% employed 96% self idencfy as gay 47% in a relaconship Median of 10 partners in last 90 days (baseline) Median of 5 as recepcve; 5 as insercve partner Median of 2 partners for condomless sex as recepcve and 3 as insercve partners 40% used PEP in last yr 21% more than once hkp:// MonicaDesai.pdf

20 Next steps Recruitment closed April 2014 Follow up will concnue for 2 years (to April 16) Negocacng access to Truvada for all parccipants uncl end of study Jan 14: applied to HTA NIHR for trial funding to enrol a further 1800 men

21 PROUD CEG & PPI Community Engagement Group: NAM, NAT, THT, GMFA, LGF, MESMAC, NAZ Sept 2013: UK s leading HIV charices release joint posicon statement on PrEP Public Involvement: via CEG partner organisacons Parccipant Involvement: via in- person and web- conference meecngs hkp://

22 Healthcare providers knowledge of, attitudes to and practice of PrEP Design: anonymous cross-sectional survey of sexual health care providers Recruitment: Sept-Nov 2013 from professional societies, conferences and social media Sample: Doctor (59%), Health adviser (19%), sexual health nurse (16%), other (6%) Female 64% and male 36% 35% under 39yrs old, 35% aged 40-49, 31% aged 50 or above 27% involved in PROUD; 73% not

23 KAP findings 28% report high knowledge highest among doctors (39%) 58% felt able to discuss with patients highest among doctors (73%) 43% not involved with PROUD had been asked about PrEP in last year 54% supported availability of PrEP lowest for doctors (41%) 78% supported targeted provision to higher risk groups

24 KAP findings 53% question if effective prevention tool in real world 80% reluctant to prescribe without UK specific guidance 42% concerned that PrEP may result in increase of STI 29% concerned about impact of PrEP on ART resistance 67% confident Truvada safe as PrEP 56% believe PrEP better option than PEP for frequent PEP users

25 Quescons going forward UK guidance: in absence of clinical trial Equity: access to who and where Control: future trials plus SoC Terminology: unprotected v condomless sex Messages: complicacon thereof Scgma: why are you taking that poison

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27 "If something comes along that's beker than condoms, I'm all for it, but Truvada is not that," said Michael Weinstein, president of the AIDS Healthcare Foundacon. "Let's be honest: It's a party drug." Why I Started a Pe::on to Remove the Head of the AIDS Healthcare Founda:on

28 Upcoming publicacon Biomedical Preven:on: State of the Science; S McCormack, M Gafos, M, MS. Cohen in Clinical Infeccous Diseases Healthcare workers knowledge of, ajtudes to and prac:ce of pre- exposure prophylaxis for HIV; M Desai, M Gafos, D Dolling, S McCormack, A Nardone

29 What issues does PrEP raise for the UK CAB?

30 SPARE SLIDES

31 PrEP in USA FDA approved Truvada July 2012 Prescribers survey (01/11 03/13) 55% of all US pharmacies responded 1,774 individuals: 150 in 2011, 1,274 in 2012 and 350 in Q % prescribers have not prescribed ARV before 12% Infeccous Diseases 48% scripts for women

32 Project Pop. Design/key ques:ons Status The Demo Project MSM/TGW 600 HIV- negacve MSM/TGW at clinics in 3 cices. East Bay Consorcum LAC PATH PrEP Demo Project Accve Linkage, Engagement & Retencon to Reduce HIV (ALERT) CDC Foundacon Demonstracon Project USA Demonstracon Studies (8) Young MSM of color MSM/TGW MSM MSM and heterosexual woman Oct 12; Aug 14 Test and link YMSM of color to services; Dec 2012 A customized prevencon package that may include PrEP. Randomized to evaluate text messaging based adherence May 13; May 17 Jan 13; Oct parccipants in health clinic se ngs Pending funding. SPARK Project NYC MSM/TGW Idencfy social/behavioral factors associated with disparices in access Project PrEPare Young MSM PrEP among YMSM who are at risk for HIV infeccon HPTN 073 Black MSM Assess the inicacon/acceptability/ feasibility for BMSM. Oct 2013 Nov 12; Nov 15 July 13; June 15

33 Project Country Pop. Design/key ques:ons Status iprex OLE Br, Pe, Eq, SA, Th, US MSM/TGW Open Label extension Enrolled; Nov13 TDF2 FU Bots Hetero Open Label extension Nov12; Nov13 Bangkok FU Thailand People who inject drugs Partners PrEP Kenya & Uganda Open Label extension Q4 13; Q4 14 SD PrEP as bridge to ART. Aug 13; CHAMPS South Africa Hetero adol Prevencon menu for adolescents July 11; June 15 WRHI South Africa FSW PrEP and TasP as combined prevencon and care LVCT and SWOP Naconal Agency Durbar & Ashodaya Samithi Victorian PrEP Demo Project PrEP Demonstracon Studies (10) Kenya Women, FSW, MSM Introduce PrEP into combinacon prevencon Nigeria SD PrEP and TasP as combined prevencon and care Feb 14; Sep 16 Feasibility results Dec Formacve India FSW&T PrEP intro Feasibility results Oct Australia At- risk populacons PrEP effeccveness of PrEP Funded; to run three years.