TB/HIV ResearchApproaches 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

Informationas

InterventionDini 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 RatesGeorgia Compared with U.S.

Approaches (2)

Western Europe520 000 – 680 520 000 – 680

000000North Africa & Middle

East470 000 – 730 000470 000 – 730 000

Sub-Saharan Africa25.0 – 28.2 25.0 – 28.2

millionmillion

Eastern Europe & Central Asia1.2 – 1.8 1.2 – 1.8 millionmillion

South & South-East Asia

4.6 – 8.2 4.6 – 8.2 millionmillion

Australia & New Zealand

12 000 – 18 00012 000 – 18 000

North America790 000 – 1.2 790 000 – 1.2

millionmillionCaribbean350 000 – 590 000350 000 – 590 000

Latin America1.3 – 1.9 million1.3 – 1.9 million

East Asia & Pacific700 000 – 1.3 700 000 – 1.3

millionmillion

NNRTI Response StudyObservational 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.

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International Union Against Tuberculosisand Lung Disease

Study AReport of a Controlled Clinical Trial of

Two Durations of Chemotherapy for the Treatment of Tuberculosis

Amina Jindani, Andrew Nunn, Donald EnarsonFor 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 TBTC Mission: “… to conduct programmatically programmatically relevantrelevant clinical, laboratory, and epidemiologic clinical, laboratory, and epidemiologic research concerning the diagnosis, clinical research concerning the diagnosis, clinical management, and prevention of tuberculosis management, and prevention of tuberculosis infection and disease.”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-resistant -tuberculosis (MDR-TB) [pdf 51kb]The Stop TB Working Group on DOTS-Plus for MDR-TB. International -Journal of Tuberculosis and Lung Disease 2003, 7(5): 410-414.

In addition, a database on global MDR-TB research activities has been created with the following purpose:

World Health Organization

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WHO> WHO sites

http://www.who.int/tb_search/

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

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About WHO

Countries

Health Topics

Publications

Research tools

WHO sites

WHO> WHO sites

http://www.who.int/tb/dots/dotsplus/management/en/

Feedback loop

Programimplementation

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

Programimplementation

Evaluation and operations

research

Policy definition/revision

Feedback loop

Programimplementation

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