THE FRENCH NATIONAL AGENCY FOR RESEARCH ON AIDS & VIRAL HEPATITIS

1. THE FRENCH NATIONAL AGENCY FOR RESEARCH ON AIDS & VIRAL HEPATITIS Dr Didier Laureillard, ANRS, HCMCdidier.laureillard@anrs.fr Titre document / Le 15 - 09 - 2013

2. Introduction Public agency, created in 1992, aimed at funding and coordinating research in all areas relevant to HIV/AIDS and viral hepatitis As of 1/01/2012, an autonomous agency within INSERM (Institut National de la Santé et de la Recherche Médicale) in 2013 Annual budget of research: 48 Millions € (total equivalent to 125 millions €) Supported by: Ministry of Research (39M€) Ministry of Health Ministry of Foreign Affairs Institutional partners : INSERM, CNRS, Pasteur Institute, IRD, Esther Scientific Advisory Board: 50% of whose members are from outside France President: Pr Françoise Barré-Sinoussi

3. ANRS Scientific Advisory Board

4. Commitment to all areas of research Basic research Vaccine research Clinical, therapeutic and epidemiologic research Research in public health and the human & social sciences Research in resource limited countries

5. Researchers are : clinicians, biologists, social science specialists They are based in the laboratories of INSERM, CNRS, Pasteur Institute, IRD, and universities and hospitals Some of them are not working in France but are based in other countries Who are the researchers ?

6. ANRS « Scientific performance » 550 publications/year Approximately 50% of publications have IF > 5. 1% of ANRS publications are in the 10 top international journals 6,2% of ANRS publications (HIV/AIDS and hepatitis) are in the 1% group of excellence (number of citations), higher than the national average in the field of biology/health France is ranked 2nd or 3rd international position in the field of HIV and 2nd in the field of hepatitis

7. ANRS Funding Mechanisms 2 main calls for proposals/year Top-down vaccine research programme Clinical Trials: AC5/AC24 committees for approval and funding ANRS: essentially only funder for HIV and viral hepatitis research in France ANRS: funds research, but not institutions, nor salaries

8. % Distribution of funds according to research area 2012 (44 M €) Basic Science HIV 14 % Vaccine HIV-HCV 12 % Clinical trials and cohorts (HIV) 26 % Epidemiology/socio-behavioral science 7 % Resources limited countries (HIV-Hepatitis) 22 % Hepatitis B and C 19 % GLOBAL HEPATITIS 24% (11 M €) GLOBAL BASIC SCIENCE : 39% (17 M €)

9. 4 main ANRS priorities HIV Study reservoirs with the objective of eradication or functional cure Testing: Novel methods; Early and better treatment Prevention of new infection with a biomedical approach Develop new vaccine strategies With a NORTH   SOUTH vision Integrating economic aspects

10. Molecular mechanisms involved in cell-virus interactions Relationships between fibrosis, inflammation and viral replication Strategic evaluation of new molecules anti HVC (Cohorte, co-infections...) New tools for prevention HBV Cure 5 main ANRS priorities Hepatitis • + research priorities in Social and Health Science: • - Hepatitis B and C among drug users and inmates • - Screening strategies of HCV and HBV chronic infection, including rapid tests, • - Modeling of HCV transmission among drug users

11. Research in resource-limited countries

12. Developping countries department By 1994, the ANRS started to fund research projects in many resources-limited countries, and has set up sites in Africa, Asia and South America A specific department and a specific scientific and review board (CSS6) were set up • 2 calls for grant/year: 15 of March & 15 of September • In 2012: ¼ of its budget (ie, ≈12 millions €) to research on HIV/AIDS and viral hepatitis in these countries • ≈ 70 ongoing projects

13. ANRS in resource limited countries

14. Ongoing projects in resource limited countries in 2013

15. ANRS in Viet Nam

16. Introduction Collaborations between French and Vietnamese researchers began in 1988. 6 January 2000: official agreement between Vietnam Ministry of Health and ANRS for collaboration and creation of an ANRS site in Viet Nam Most ANRS-funded studies were conducted in Ho Chi Minh City, with support from Pasteur Institute and the city’s hospitals, in the framework of national (VAAC) and provincial (PAC) programs in the fight against HIV/AIDS. The studies now extend to the north of the country, notably in Hài Phòng. 13th of March 2014: Official agreement for collaboration with Hanoi Medical University

17. ANRS Site Coordinators

18. More than 10 years of collaboration Training & technology transfer Social sciences - Sexual behaviors & HIV/AIDS - Social determinants of access to care for children living with HIV 2 projects Basic research Biological characterizations of HIV-1 Immune & genetic determinants of protection 7 projects Clinical research Improving diagnostic & treatment of patients infected by HIV & associated diseases (TB, Hepatitis…) 14 projects (5 ongoing) 18

19. ANRS France Ministry of health Vietnam A lot of partnerships Co-ordination Truong Xuan Lien & F.Barre-Sinoussi • Pasteur Institute HCMC • Health service HCM & Hải phòng • PAC HCMC & Hai phong • Pham Ngoc Thach Hospital • Pediatric Hospital n°1 & 2 • National Pediatric Hospital • OPC HCMC & Hải phong • Việt Tiệp Hospital Hai phòng • Medical University Hải phòng • Southern Institute of Social Sciences • Vietnamese academy of social sciences • Institute for Population and Social • Studies, National Economics University • Institut Pasteur Paris • Université d’Aix Marseille III • Université Victor Segalen, Bordeaux • Kremlin Bicêtre hospital, Paris • European G.Pompidou hospital, Paris • Necker hospital, Paris • Pitié-Salpétrière hospital, Paris • Saint Antoine hospital, Paris • INSERM • Montpellier medical University • IRD, Marseille et Montpellier • ESTHER 19

20. ANRS funded ongoing projects in Viet Nam

21. ANRS 12150 – RAP Pharmacokinetics of rifabutin with antiretroviral therapy in the treatment of tuberculosis patients with HIV infection in in Ho Chi Minh City • 33 TB-HIV co-infected patients enrolled • End of clinical activities: october 2012 • Presentation of results : • Ethic paper published to « Public Health Action » – June 2013 • Poster at IAS conference – July 2013 • Oral presentation at World TB Union conference – Paris, October 2013 • Princeps paper published in « PLoS One » – January 2014 • PK-genomics analysis still on-going

22. Improving diagnosis of Tuberculosis in HIV-infected children in Asia & Africa with alternative specimen collection methods (string test, nasopharyngeal aspirate) and Xpert MTB/RIF assay PAANTHER 01 – ANRS 12229 Pediatric Asian African Network for Tuberculosis and HIV Research • 420 HIV-infected children with suspicion of TB • 4 countries: Burkina Faso, Cambodia, Cameroun, Vietnam • Principal objective:Develop a diagnostic algorithm to improve the diagnosis of TB in HIV-infected children • In Vietnam, HCMC: • 3 hospitals : Pham Ngoc Thach hospital, Nhi Dong 1, Nhi Dong 2 • Enrolment started in September 2012 • 108 children enrolled • End of enrolment: June 2014End of the study: December 2014

23. ANRS 12290 –STATIS Systematic empirical vs. Test-guided Anti-TB Treatment Impact in Severely immunosuppressed HIV-infected adults initiating ART with CD4 <100/mm3 • Multi-countries, two-arm, unblinded,randomized, superiority trial: Ivory Coast, Cambodia, Cameroun, Uganda, Vietnam • Principal objective: To compare the 24-week risk of death and occurrence of invasive bacterial infection between 2 experimental strategies :  continuous extensive TB screening (chest X-ray, Xpert, urine LAM) during follow-up when the patient present symptoms  systematic empirical TB treatment (2ERHZ/4RH)started 2 weeks before ART initiation • Specific objectives: Mortality, bacterial infections, loss-to-follow-up, morbidity, tolerance of TB treatment, efficacy of ART, care consumption, cost-effectiveness of the strategies.

24. ANRS 12290 –STATIS Systematic empirical vs. Test-guided Anti-TB Treatment Impact in Severely immunosuppressed HIV-infected adults initiating ART with CD4 <100/mm3 • 1050 HIV-infected adults (CD4<100/mm3), naïve of ART • In Vietnam, Pham Ngoc Thach hospital, HCMC: • 300 patients • Process of submission to ERB MOH • First patient enrolled September 2014 • Inclusion time: 24 months • End of follow-up: August 2017 • First results: December 2017

25. ANRS 12300 –REFLATE TB 2 Non-inferiority of TDF/3TC & Raltegravir 400 mg BID compared to TDF/3TC/Efavirenz in ART naïve HIV-infected patients receiving Rifampicin TDF245mg qd + 3TC 300mg qd + EFV 600 mg qd 1:1 • 460 patients • VIH-1 • ART naïve • Tuberculosis • RIF containing regimen TDF245mg qd + 3TC 300mg qd + RAL 400 mg bid RHZE 2mo followed by RH 4mo W 24 W0 W48 Phase 3 randomized trial in Brazil, France, Ivory Coast, Mozambic, Vietnam Primary endpoint HIV RNA<250 copies/mL

26. ANRS 12262 –FIBRHIVIET Study Pilot Study on clinical and virological characteristics of HIV-HCV co-infected patients in Hai Phong • Main objective: To describe clinical and virological characteristics of HCV/HIV co-infected patients followed in Viet Tiep Hospital and potentially eligible for a HCV treatment • Specific objectives: • To determine the proportion of patients with active HCV infection • To determine the genotype distribution of HCV infection • To assess the severity of liver fibrosis • To study factors associated with severity of liver fibrosis • Cross-sectional study in 111 HIV/HCV co-infected patients • Just finished clinical & biological activities  Analysis ongoing

27. ANRS 12299 –DRIVE-IN Study Feasibility phase of an interventional project to reduce HIV incidence among people who inject Drugs in Hai Phong, Viet Nam • Approved by ANRS in July 2013 • Primary Objective: To assess the efficacy of a combined preventative intervention targeting PWID on the reduction of HIV incidence. • Secondary objectives: To estimate the impact of the intervention on HCV incidence, To estimate the overall HIV and drug-related morbidity and mortality, To identify the determinants of risk and harm reduction seeking behaviours,...) • Primary objective: to evaluate the feasibility of implementing an interventional cohort of PWID in Hai Phong by demonstrating that enrolment and follow-up of various hard-to-reach subgroups of PWID is feasible in the local context. • Sponsored by ANRS, funded by ANRS & NIDA • 600 participants to the RDS study, then 250 participants followed 6 months • Agenda: • Submission to IRB HPMU next week • First patient enrolled September 2014 • Inclusion time: 6 months • End of follow-up: May 2015

28. Research priorities in Vietnam • Related to the National HIV/AIDS Research Agenda • Basic sciences, epidemiology, clinical trials, social science, … • At this moment: • Interventions in most at risk populations, notably PWUDs (ex: “Test and Treat strategy”) • Co-infection with Tuberculosis (ex: “Phase III with rifabutin”) • Viral hepatitis C (ex: “Pilot project on HCV treatment in HIV-coinfected patients”) • But others topics possible

29. Process to obtain ANRS funds for research project • 2 call for grants/year: • Deadline 15th of March & 15th of September • Specific forms for submission (available on ANRS website, in French) • Submission in English OK • 2 Principal Investigators: 1 from Vietnam and 1 from France • Max: 36 months project • Review by an independent scientific Committee (CSS6): • Meetings in June & December • Answer 1 month later (positive in 25-30%) • If needed: Help from ANRS site coordinators (finding French partners, writing protocol, submission, …)

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