Engaging in HIV Cure Research Understanding Current and
- Slides: 16
Engaging in HIV Cure Research: Understanding Current and Future Scientific and Clinical Challenges Gaps and Community Engagement July 19, 2016 Robert Reinhard Community Liaison Canadian HIV Cure Enterprise (Can. CURE) & NIH MDC BELIEVE Cure Collaboratory #AIDS 2016 | @AIDS_conference
Financial Disclosures/COI I have no financial disclosures No COI #AIDS 2016 | @AIDS_conference
Overview of Talk Since 2009, * engagement has not kept pace alongside progress of investigator initiated cure research to: 1. Include global “cohorts” or characterize their biology/physiology and their lives 2. Advance critical topics of public discussion 3. Include other relevant virus/host studies in research that are crucial to achieve safe, accessible, scalable cure *D D Richman et al. Science 2009; 323: 1304 -1307 #AIDS 2016 | @AIDS_conference
Operational Terms 1. Engagement vs. Education vs. Recruitment Lo, et al. AIDS Patient Care and STDS (2015) 2. Cure Research With Human Participants • Sampling cells from blood and tissue* • Interventions and Strategies Lab Clinic *Including opportunistic biopsy/sampling, autopsy, etc. [IAS 2016 Conf: WEAA 0106 LB “HIV Cure research in a novel population of South African hyper-acute HIV infections detected in the blood donation setting: the Monitoring and Acute Treatment of HIV Study (MATHS”)] #AIDS 2016 | @AIDS_conference
1. Global Cohorts • Who is being cured and what concepts are investigators proving in early stage research? • Different global life expectancies: surrogate markers for biology and how life is lived #AIDS 2016 | @AIDS_conference
Life Expectancy: What’s Behind the Results? Figure Copyright © 2015 Egger et al. Open Access article distributed under the terms of CC BY-NC-ND Terms and Conditions The Lancet Global Health 2015 3, e 122 -e 123 DOI: (10. 1016/S 2214 -109 X(14)70383 -3)
Trends in life expectancy of HIV-positive adults on antiretroviral therapy Wandeler, Gilles; Johnson, Leigh F. ; Egger, Matthias. Curr. Opinion HIV/AIDS. epub May 31, 2016 #AIDS 2016 | @AIDS_conference
2. Advancing Discussion Topics IAS 2016: Community Engagement and Ethics in Cure Research THPDD 01 Incl Abstract 3813 #AIDS 2016 | @AIDS_conference
Social SNPs ‘“You would really have to convince them that stopping treatment would not make them sick again. ”’ “The psychological impact of becoming ill again in the event of failure of the proposed “cure” would be enormous. ” “Participants became tearful and distressed when reminded that a cure was only a possible event in the distant future. ” #AIDS 2016 | @AIDS_conference
Social SNPs • “It was critical to also think about prevention, treatment and cure as always existing in relation to each other. ” • “Activists, communities, and civil society groups have had very little involvement so far in developing, driving and shaping the cure research agenda. ” #AIDS 2016 | @AIDS_conference
3. Immunology/Virology Research Gaps RESEARCH GAP 1. Adult age Δ (20 -60+ yrs) 2. Adult vs. Pediatric LITERATURE N Chomont – IAS 2015 (TUSAO 604) Co-infection Esp TB, Malaria, Hep I Sereti (2015)J Vir Erad; KC Jambo (2014)Muc Immunol; SK Cribbs (2015) AIDS Res Human Ret; A Saeidi (2016) J Leuk. Biological sex and gender use of hormones J Karn IAS 2015 (abstract #TUAA 0205 LB); AM Gomez (2015) J Immunol; S Ziegler (2016) Curr Op HIVAIDS 1. Immunological discordance with VL suppression: 10 -20% of PLWH; 2. Persistent low level viremia (100 -1000 c/ml) Clade/Subtype matters Poly “pharmacy” nonmedical use of drugs #AIDS 2016 | @AIDS_conference G Khoury (2016) AIDS; TW Chun (2002) JID; TW Chun (2011) JID J Saison (2013) J Med Virol; L Bhoopat (2006) Mod Pathol; N Kinloch IAS 2016 ? WEPEA 002 Intentionally left blank
New IAS Global Scientific Strategy Deeks, et al. Nature Medicine (2016) doi: 10. 1038/nm. 4108, epub. July 11 Emphasis should be placed on exploring how human variability (for example, host genetics, age, gender, co-morbidities, co-infections, HIVdisease-progression state and the microbiome) affects HIV persistence on ART. Given that the majority of those infected with HIV are chronically co-infected with other pathogens, such as malaria, Mycobacterium tuberculosis, hepatitis B or C virus or helminthic worms, the impact of such co-infections on the persistence of HIV should also be studied. #AIDS 2016 | @AIDS_conference
What To Do Connecting the Future With Now Examples for engagement discussion: • Antibodies as interim long acting treatment to reduce VL and later for cure • DTG and fitness • Reducing inflammation to improve health and to limit infectivity and reservoir • Early ART: preserve CTL response/minimize reservoir now to achieve a cure later #AIDS 2016 | @AIDS_conference
Good Engagement Practice FRESH and Hyperacutes Baraza - HESN/FSW - Kenya ART and Antibody Videos • • • https: //www. youtube. com/watch? v=o. Nfw 9 n 5 n. Bt. U https: //youtu. be/z. Z 3 gi. Yhr. IZE http: //www. croiwebcasts. org/console/player/29435? media. Type=podium. Video& #AIDS 2016 | @AIDS_conference
Takeaway Messages • Proofs of concept should match real life cohorts biologically and socially • Delay in concepts and engagement of cohorts carries risks for progress in remission research • Research immune system of the hard cases along with nonconfounded ideal • Make it real now not after the home run #AIDS 2016 | @AIDS_conference
Great Thanks Renée Masching Ron Rosenes Tola Mbulaheni Shari Margolese Jonathan Postnikoff José Sousa Wangari Tharao Darien Taylor Éric Cohen Nicolas Chomont Keith Fowke Sébastien Sabbagh Steering Committee National Investigators #AIDS 2016 | @AIDS_conference Rosanne Lamplough George Washington University Anna-Laura Ross Doug Nixon Brad Jones IAS 2015 Global Stakeholders Workshop Andy Lambert University of Toronto Matt Sharp Mario Ostrowski Judith Auerbach Rupert Kaul Bruno Spires Shariq Mujib University of Melbourne Sharon Lewin
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