New TB/HIV Working Group Report: Priority Research Questions for TB&HIV in HIV-Prevalent and Resource-Limited Settings

In November 2008, the Global TB/HIV Working Group of the Stop TB Partnership, in collaboration with the WHO Stop TB and HIV/AIDS departments and the UNDP/UNICEF/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR) called for the revision of the 2005 TB/HIV research priorities agenda for resource-limited settings.

A literature review was conducted to assess the current state of research and to identify knowledge gaps in six key pre-defined areas of TB and HIV co-infection:

1. TB prevention
2. intensified TB case-finding
3. TB treatment in people living with HIV
4. drug-resistant TB and HIV
5. childhood and maternal TB and HIV
6. integration of TB and HIV services.

The results of the literature review, together with discussions held during an international meeting on TB/HIV research issues in Cape Town, South Africa in July 2009 form the basis of the document.

The process was advised by international TB and HIV experts in a form of an Advisory Group and a Peer Review Committee. Members included technical experts and researchers in the field of TB and HIV, health policy-makers, people living with HIV and their advocates, TB and HIV programme managers, representatives of donor agencies, and WHO staff. Members of the Advisory Group and the Peer Review Committee were asked to list their three top-priority questions under each pre-defined area based on their review of the document and their expert view. This allowed the committee to compile a list of 77 questions for all areas. These questions were then rated for prioritization based on defined criteria that considered effectiveness, deliverability, answerability and equity issues. Priority scores were eventually produced by calculating the mean of the scores for each of the 77 questions, and questions were ranked under each area based on the score. A password protected web-based consultation system was used for the prioritization process.

The top research questions for TB prevention among people living with HIV include:

1. What is the optimal TB screening algorithm to be used across different settings, with different TB and HIV disease burden, to safely initiate preventive TB therapy?
2. What is the best infection control interventions that effectively reduce M. tuberculosis transmission in health-care settings, at home and in the community?
3. What is the optimal duration, safety, efficacy and cost-effectiveness of isoniazid preventive therapy alone or added with antiretroviral therapy in reducing the risk of active TB compared to antiretroviral therapy alone among people living with HIV, particularly under programme conditions?

In the area of intensified TB case-finding, the top research questions are:

1. How to develop a simple and rapid point-of-care “TB dipstick test” to diagnose all types of TB in all patients, including children and people living with HIV?
2. What is the optimal TB screening and diagnostic algorithm for use across all settings with different HIV and TB diseases burdens to enable screening of all forms of TB, and that can be integrated into routine care?
3. What is the programmatic impact of the most promising diagnostic tools currently available for rapid TB diagnosis, including diagnosis of drug resistance and of smear-negative patients identified through large-scale evaluation studies were identified as priorities?

In the area of TB treatment for people living with HIV, the top priority questions are:

1. What are the safety, efficacy and pharmacokinetic parameters of new and novel drugs that could replace rifampicin and shorten TB treatment, to cure susceptible and drug-resistant TB in people living with HIV, with or without antiretroviral therapy?
2. What are the best first and second-line antiretroviral therapy regimens in terms of safety, efficacy, tolerability, optimal dosage of drugs and drug interactions, to use in combination with a rifampicin-based TB regimen?
3. What is the optimal time to start antiretroviral therapy in HIV-infected patients who have active TB disease, both drug-susceptible and drug-resistant types?

The three top-priority questions for drug-resistant TB and HIV infection are:

1. What is the programmatic impact and benefit to individual treatment outcomes of line probe assays and other non-culture-based assays for diagnosis of drug-resistant TB at the peripheral level of care?
2. What are the true burden, predictors and transmission dynamics of MDR-TB and XDR-TB in high HIV prevalence and resource-limited settings?
3. What is the best model of care for drug-resistant TB in settings with high burden, in light of basic public and individual patient rights?

Under maternal and childhood TB and HIV coinfection, the priority questions identified include:

1. What is the best clinical algorithms and diagnostic tools to improve TB screening and diagnosis in HIV-infected infants and children, including diagnosis of BCG-related TB, TB-IRIS and drug-resistant TB?
2. What is the effect of antiretroviral therapy in preventing TB in children?
3. What is the optimal antiretroviral therapy to use in combination with a rifampicin-based TB regimen in HIV-infected infants and children and the optimal time to initiate antiretroviral therapy in children being treated for TB?

The research priorities identified in the TB and HIV services integration area include:

1. What are the best strategies and optimal models to integrate and deliver joint TB/HIV interventions, including antiretroviral therapy, at community and health sector levels to HIV-infected TB adults, children and families?
2. What are the best operational models to increase and scale-up laboratory capacity, including implementing new TB diagnostic techniques and drug-susceptibility testing, and improve diagnosis of TB at all levels of care?
3. What are the barriers to HIV care for people living with HIV, adults, children and families; what are the barriers to access to HIV and TB care, and antiretroviral therapy for those coinfected with TB, from patient and health-care worker’s perspective; and how to address these barriers?

The priority questions reflect a wide range of research needs in basic, epidemiology, clinical, and operational research. Implementation of these research priorities should capitalize on financial resources mobilized through the Global Fund for AIDS, Tuberculosis and Malaria, and the United States President’s Emergency Plan for AIDS Relief (PEPFAR) among others. Concomitant to increasing the scientific interest of the research community towards these questions, enhancing fund allocation by national governments of resource constrained settings is very crucial. It is believed the priority research questions identified in this document provide guidance on what needs urgent scientific interest and funding to address the dual TB and HIV epidemic.

Click to download the document in English or French or visit the TB/HIV Working Group website of the Stop TB Partnership.