1. HIV Research in International Settings Wafaa El-Sadr, MD, MPH Columbia University

2. Overview of Presentation Status of HIV epidemic HIV-related research – where done and who is doing it Priority questions– implementation science Challenges and solutions Conclusions

3. Total: 33.3 million [31.4 million – 35.3 million] Western & Central Europe 820 000 [720 000 – 910 000] Middle East & North Africa 460 000 [400 000 – 530 000] Sub-Saharan Africa 22.5 million [20.9 million – 24.2 million] Eastern Europe & Central Asia 1.4 million [1.3 million – 1.6 million] South & South-East Asia 4.1 million [3.7 million – 4.6 million] Oceania 57 000 [50 000 – 64 000] North America 1.5 million [1.2 million – 2.0 million] Central & South America 1.4 million [1.2 million – 1.6 million] East Asia 770 000 [560 000 – 1.0 million] Caribbean 240 000 [220 000 – 270 000] Adults and children estimated to be living with HIV  2009 UNAIDS, 2010

5. Antiretroviral Therapy by Region--2001

7. Number of PLWH receiving ART in low- and middle-income countries, by region, 2002–2009 UNAIDS, 2010

8. Change in HIV Incidence UNAIDS, 2010

9. HIV Treatment Coverage in Low & Middle Income Countries WHO Towards Universal Access 2010

10. Coverage of HIV Prevention– Low Resource Countries, 2004-2009 Source: UNAIDS/WHO, 2010 0% 20% 40%60%80%100% HIV testing Antiretroviral Drugs for PMTCT Condom Use Contraception for PMTCT 2004 9%32% 9% 14% 2006/7 Male Circumcision 20% 61% 70% 10% 75% 47% Unmet HIV Prevention Need 72% Estimates of CoverageUnmet HIV Prevention Need 5% 15% 20% 2009 53% 39% 25% 30% 28% Adapted Ward Cates

12. CROI 2011 Oral Abstracts

13. Oral Posters

14. International Scholars

15. The study of methods to improve the uptake, implementation and translation of research findings into routine and common practices with the goal of improving program effectiveness and optimize efficiency Know-Do Evidence to Program Gap Implementation Science

18. Examples of Implementation Science Questions Questions Which TB/HIV integration model produces the best clinical and public health outcomes yet remains efficient and scalable? What are specific strategies to increase adherence/retention in a particular program? What is the balance of fixed and mobile clinics that will most effectively allow for rapid acceleration of task shifting and decentralization of HIV care and treatment services? What is the essential package of laboratory monitoring needed for patients and how does it vary by stage of HIV disease Adapted Padian et al, JAIDS 2011

19. Countries with ICAP-Supported Programs TUNISIA MOROCCO SAHARA ALGERIA MAURITANIA MALI NIGER LIBYA CHAD EGYPT SUDAN ETHIOPIA DJIBOUTI ERITREA SOMALIA KENYA TANZANIA DEMOCRATIC (ZAIRE) CENTRAL RWANDA GABON EQUATORIAL ANGOLA CONGO NIGERIA BENIN DTVOIR E SIERRA SENEGAL GHANA THE GUINEA LIBERIA CAMEROON MALAWI ZAMBIA MOZAMBIQUE MADAGASCAR ZIMBABWE BOTSWANA SWAZILAND LESOTHO NAMIBIA ANGOLA WESTERN UGANDA OF THE CONGO REPUBLIC BURUNDI GUINEA REP. OF TOGO COTE BURKINA GUINEA LEONE GAMBIA BISSAU SOUTH REPUBLIC AFRICAN THE AFRICA KYRGYZSTAN TAJIKISTAN KAZAKHSTAN UZBEKISTAN TURKMENISTAN

20. ICAP International Research Portfolio 40 active protocols 9 countries 4 studies with a multi-country component CountryNo. of studies DRC1 Ethiopia1 Ivory Coast4 Kenya2 Mozambique7 Rwanda10 South Africa2 Swaziland6 Tanzania5

21. Models for Improving Loss-to-follow-up in the Democratic of Congo (DRC) Strengthening HIV Test Acceptance and Treatment Uptake Study (STATUS) Epidemiology of HIV-2 or HIV-1/HIV-2 infected patients in Ivory Coast How to Optimize PMTCT Effectiveness (HOPE) Project in Ivory Coast An Evaluation of Enhanced Tuberculosis Case-finding to Reduce Mortality Among Persons With Advanced HIV Presenting For HIV Care in Emergency Plan Countries (EMRG) Identifying Optimal Models of HIV Care approaches in sub-Saharan Africa Development, implementation and evaluation of a comprehensive Prevention intervention in Care and Treatment Settings (PiCTS). Kenya, Tanzania Establishment of sentinel cohorts of patients enrolled in HIV care and treatment services in Mozambique Assessing enablers and barriers to the implementation of complex PMTCT regimens and ART in pregnancy in Mozambique Evaluation of a symptom based flowchart for tuberculosis diagnosis in children in Mozambique Quality of HIV counseling and testing in maternity in Mozambique The role of Traditional Birth Attendants (TBA) in active defaulter tracing and adherence programs in Mozambique Mother-infant pair linkage using paper-tracking systems in Mozambique Evaluate TB screening of pregnant women at two PMTCT sites in Gaza Province in Mozambique Qualitative study of ART adherence in Mozambique Evaluation of a new patient tracking system on patient care and perceptions of care in Mozambique Sharing HIV/AIDS responsibility Efforts (SHARE) in Nigeria Evaluating adherence to antiretroviral therapy among HIV care and treatment patients in Rwanda Smear negative and extra pulmonary tuberculosis diagnosis and outcomes in Rwanda Operating characteristics of a screening instrument for the detection of active tuberculosis in adult outpatients with HIV infection in Rwanda Evaluation of TB screening approaches for HIV-infected children in Rwanda Estimating HIV incidence in two populations in Rwanda: High-risk women and female VCT clients- Project Ubuzima in Rwanda Peer Educator for Adherence, Referral and Linkages Program Evaluation (PEARL study) in Rwanda National Pulmonary Tuberculosis Prevalence Survey in Rwanda Assessing HIV Prevention, Care & Treatment at Sites Supported by Columbia University-International Center for AIDS Care and Treatment Programs (ICAP) in Rwanda Evaluation of the quality of the national antiretroviral treatment program in Rwanda, 2004 - 2005 Evaluation of access and utilization of PMTCT services in Rwanda BED and A1 Assay Validation Work, Kigali Incidence Study -- Project Ubuzima, Kigali, Rwanda Evaluation of Access to and Acceptance of HIV Counseling and Testing Among Patients with Tuberculosis in Rwanda Operating characteristics and effectiveness of a screening instrument for the detection of active tuberculosis in adult outpatients with HIV infection in the Eastern Cape, South Africa Design, implementation and assessment of a nurse mentor training program in HIV care and treatment in Eastern Cape, South Africa Swaziland HIV Incidence Measurement Survey (SHIMS) Swaziland National ART Program Evaluation: Treatment Outcomes and Cost-Effectiveness during 2004-2009 Swaziland in-service HIV training assessment Assessment of impact of the ART Program on people receiving Anti-Retroviral Therapy in Swaziland following six years of ART implementation in the country Feasibility Pilot of the Evaluation of Expert Client Program: Swaziland National ART Program Etiologic Survey for Genital Infections Among HIV-infected Adults Entering HIV Care: A Pilot Study in Tanzania HIV Combination Prevention in Tanzania Neonatal Circumcision Situation Assessment in Tanzania

22. A range of methodologies… Qualitative methods – Key informant interviews – Focus group discussions Quantitative methods – Group randomized studies – Cohort studies – Cross-sectional surveys Data collection – Questionnaires/interviews with patients and health workers – Data abstraction from routinely collected data – Site characteristics assessment tools

23. GCP Training Barriers –Non- Anglophone investigators have difficulty completing GCP training – Module content and examples are US focused and not relevant to international research –Field internet connections hinder completion of web courses Suggestions –Consider translated modules e.g. French and Portuguese –Design modules with international focus appropriate for international investigators –Adequate local training given at the time of study launch rather than required early in the process

24. The Protocol Approval Process Multiple levels Local and international

25. Multiple IRBs Review Processes Synchronizing reviews, comments and versions – If submissions are simultaneous, different IRBs will provide feedback at different times – If submissions are done consecutively, the process takes more time – Deciding which IRB to submit to first: For example, CU IRB usually gives more comments requiring protocol changes yet requires local IRB approval before they provide final approval

26. Field implementation of IRB requirements Getting timely approvals when there is national/MoH agenda and imperatives Adhering to required formats e.g. having the international PI name on the consent form, which may conflict with local requirements Using IRB stamped versions of tools –Running out of these forms

27. Local issues Local IRBs will usually approve first time protocols within reasonable time but –Renewals/modifications may take longer in some countries –Some countries have several levels of approvals which take more time Getting certified translators to fulfill IRB requirements can be difficult with some local dialects –Example: Changana and Macua in Mozambique

28. Example: PiCTS study Multi-country multi-site PHE: Kenya and Tanzania under ICAP, + Namibia Initial IRB submission done simultaneously in Oct 08 IRB approval dates: – Kenya local IRB Jan-09 – CDC IRB Feb-09 – CU IRB Feb-09 – Tanzania Mainland IRB Apr-09 Zanzibar IRB Jun-09 Several rounds of revisions

29. Interpretation of IRB Non Human Subject Research (NHSR) determination Program evaluations can be considered NHSR even if they include interaction with human subjects (with no identifiable information) but the determination will say ‘no interaction with human subjects’ Publication of program evaluations may require additional approval but This is not the case where there is no interaction with human subjects? How to deal with publications to share local lessons learned?

31. Conclusions Substantial advances in tackling the HIV epidemic, but many unanswered questions remain Priority of pragmatic questions—implementation science Need to respond to the local circumstances and needs Importance of considering the flow of approvals Clearer definitions and interpretation of NHSR Challenge of non-traditional research Establishing responsive systems for support of international research is a key priority