TB/HIV Research Approaches and Challenges Naomi Bock, MD Global AIDS Program Centers for Disease Control and Prevention February 14, 2005

There is a clear complimentarity and inter- relationship between monitoring and evaluation (M&E), some specific surveillance activities and operational research. All derive “strategic information”, new knowledge and data that will make up the evidence base on ART delivery in resource-limited settings.

Approaches (1) D.C. State of Georgia, USA

Information as Intervention Dini et al, J Pub Health Manage Prac, 1996

Assessment Feedback Incentive eXchange Dini et al, J Pub Health Manage Prac, 1996

LeBaron et al, JAMA, 1997 Vaccination Series Completion Rates Georgia Compared with U.S.

Approaches (2) Western Europe – North Africa & Middle East – Sub-Saharan Africa 25.0 – 28.2 million Eastern Europe & Central Asia 1.2 – 1.8 million South & South-East Asia 4.6 – 8.2 million Australia & New Zealand – North America – 1.2 million Caribbean – Latin America 1.3 – 1.9 million East Asia & Pacific – 1.3 million

NNRTI Response Study Observational Study of Treatment Effectiveness and Resistance Patterns among Women Initiating Treatment with Non-nucleoside Reverse- transcriptase Inhibitor-based HAART after Previous Single Dose Nevirapine (SD NVP) in Pregnancy Welcome to the NNRTI Response Study Website. The Epidemiology Branch of the Division of HIV/AIDS Prevention and the Care and Treatment Branch of the Global AIDS Program (GAP), U.S. Centers for Disease Control and Prevention in Atlanta are jointly coordinating this study to examine the response to highly active antiretroviral therapy (HAART) that includes nevirapine (NVP) among women who have been exposed to prior single-dose (SD) NVP as compared to those who have not. This is a prospective observational study consistent with the goal to conduct clinically applicable operational research that is expected to directly inform program implementation. This study will be conducted in at least 2 sites, including Zambia and in Thailand, under the direction of the Principal Investigators listed. The sites where the study will be conducted are providing non-nucleoside reverse transcriptase inhibitors (NNRTI)-based HAART to persons attending their clinics. Some of the women attending these clinics have received SD-NVP for PMTCT in the past and others have not. This study intends to use the opportunity that has been presented at the early stage of a period of rapid expansion of antiretroviral therapy in resource- constrained settings to generate data to address the important question of response to NNRTI-based HAART therapy among women who have received SD-NVP for PMTCT as compared to women who have not. HOME CALENDAR CONTACT US PROTOCOL PROJECT MANUAL FORMS CODE BOOKS PROGRESS REPORTS

International Union Against Tuberculosis and Lung Disease Study A Report of a Controlled Clinical Trial of Two Durations of Chemotherapy for the Treatment of Tuberculosis Amina Jindani, Andrew Nunn, Donald Enarson For the Clinical Trials Programme Investigators †

The TB Trials Consortium (TBTC) Funded since 1998 by the Division of TB Elimination, CDC 28 clinical sites worldwide Links to local TB control programs TBTC Mission: “… to conduct programmatically relevant clinical, laboratory, and epidemiologic research concerning the diagnosis, clinical management, and prevention of tuberculosis infection and disease.”TBTC Mission: “… to conduct programmatically relevant clinical, laboratory, and epidemiologic research concerning the diagnosis, clinical management, and prevention of tuberculosis infection and disease.”

28 clinical sites worldwide CDC Administrative, Statistical, and Data Management Center Rio de Janeiro Barcelona Kampala Durban

Database on global MDR-TB research activities Background Currently, there is a lack of evidence available to develop policy recommendations for the management of multidrug-resistant tuberculosis (MDR-TB) in low- and middle-income settings. As a result, WHO and partners developed the DOTS-Plus strategy which is currently being tested through pilot projects and operational research activities. In order to stimulate global MDR-TB research activities the Stop TB Working Group on DOTS-Plus for MDR-TB has developed a prioritised research agenda for DOTS- Plus. -A prioritised research agenda for DOTS-Plus for multidrug-resistantA prioritised research agenda for DOTS-Plus for multidrug-resistant -tuberculosis (MDR-TB) [pdf 51kb] The Stop TB Working Group on DOTS-Plus for MDR-TB. Internationaltuberculosis (MDR-TB) [pdf 51kb] -Journal of Tuberculosis and Lung Disease 2003, 7(5): In addition, a database on global MDR-TB research activities has been created with the following purpose: World Health Organization Home About WHO Countries Health Topics Publications Research tools WHO sites WHO> WHO sites

DOTS Plus and the Green Light Committee WHAT IS DOTS-PLUS? Based upon DOTS, DOTS-Plus is a comprehensive management strategy under development and testing that includes the five tenets of the DOTS strategy. DOTS-Plus takes into account specific issues (such as the use of second-line anti-TB drugs) that need to be addressed in areas where there is high prevalence of MDR-TB. Thus, DOTS-Plus works as a supplement to the standard DOTS strategy. By definition, it is impossible to conduct DOTS-Plus in an area without having an effective DOTS-based TB control programme in place.... WHAT IS THE GREEN LIGHT COMMITTEE? World Health Organization Home About WHO Countries Health Topics Publications Research tools WHO sites WHO> WHO sites

Feedback loop Program implementation Evaluation and operations research Policy definition/revision

Challenges Local involvement Protection of human subjects

Local Involvement National / District / Local programs involved in planning as well as implementation Strengthen TB programs Avoid redirecting scarce resources Include the community of people with TB and HIV

Local Involvement National / District / Local programs involved in planning as well as implementation Strengthen TB programs Avoid redirecting scarce resources Include the community of people with TB and HIV HIV programs involved in planning, implementation, evaluation, policy

Feedback loop Program implementation Evaluation and operations research Policy definition/revision

Feedback loop Program implementation Evaluation and operations research Policy definition/revision

Challenges Local Involvement Protection of human subjects

Declaration of Helsinki “Concern for the interests of the subject must always prevail over the interests of science and society.” 1975 revision

Tuskegee Study of Untreated Syphilis Conducted –To study the natural history of untreated latent syphilis –By US Public Health Service, with support from the Milbank Memorial Fund –Beginning in 1932

Non-therapeutic lumbar puncture

Tuskegee Syphilis Ad Hoc Panel, 1973 No informed consent Vulnerable population Undue inducements - burial costs Participants not informed when penicillin therapy became available in the 1950s Participants systematically blocked from receiving treatment

In 1997, surviving participants of the Tuskegee Syphilis Study and their families gathered at the White House to witness the President's apology on behalf of the United States government

Proposed Roles of WHO Database of research studies GLC approach to those programs interested in participating in research –Program strengthening with partners –DTBE/CDC and Union operational research courses

Proposed Roles of WHO (2) Facilitating human resource expansion –Identifying training grants which fund masters or doctoral students for in-country research –Stimulating donors to create more such programs “Club” of National/District/local programs participating in research at program level, including multi-centre research