Table 1.

Key Research Questions of Importance to Integration of TB and HIV Programs in High HIV-TB prevalence settings

Collaborative TB/HIV Activities	Research question	Expected programmatic impact
A. Establish the mechanisms for collaboration
A.1. Coordinating bodies for TB/HIV activities A.2. Surveillance of HIV prevalence in TB patients A.3. Joint TB/HIV planning A.4. Monitoring and evaluation	1. What are the best models of delivery of integrated HIV and TB services which may also include maternal and child health and chronic non-communicable diseases like diabetes?	1. Increased uptake of HIV testing and care for TB patients, and better TB case finding in pre-ART and ART clinics
B. Decrease the burden of TB in PLHIV
B.1. Establish intensified TB case-finding (ICF) B.2. Introduce isoniazid preventive therapy (IPT) B.3. Ensure TB infection control (IC) B.4. Better coverage and earlier use of ART	1. Does a strategy of empirical TB treatment reduce early mortality in PLWH with low CD4+ counts who are about to start ART compared with a strategy of ICF using established or new TB diagnostic tests?	1. Reduced early mortality in PLWH starting ART
	2. Does universal HIV testing and early initiation of ART reduce individual and community risk of TB?	2. Reduced TB incidence in PLWH and high HIV-prevalence communities
	3. What is the optimum frequency of repeat ICF after baseline screening in pre-ART and ART clinics?	3. Evidence to guide baseline and serial ICF leading to increased TB diagnosis
	4. What is the most cost-effective TB diagnostic screening algorithm for ICF in pre-ART and ART clinics using smear microscopy, Xpert MTB/RIF and urine LAM?	4. Evidence to guide the strategic use of current TB diagnostic tests leading to increased TB diagnosis
	5. In health facility and congregate settings, how should TB infection control be routinely monitored, recorded and reported?	5. Better implementation of TB infection control practices
	6. Is long-term IPT in PLWH before or after the start of ART acceptable to patients and effective in reducing risk of TB without generating drug resistance?	6. Increased use of IPT which is effective and safe in reducing the risk of TB
C. Decrease the burden of HIV in TB patients
C.1. Provide HIV testing and counselling C.2. Introduce HIV prevention methods C.3. Introduce CPT C.4. Ensure HIV/AIDS care and support C.5. Introduce ART	1. Does HIV testing of TB suspects and referral of HIV-positive patients to structured HIV care lead to a better prognosis in this group?	1. Reduced mortality in TB suspects and improved likelihood of TB being diagnosed within structured HIV care
	2. What is the most effective and safest dose of rifabutin to use with protease inhibitors in second-line ART?	2. Improved treatment of TB in PLWH who have failed first-line ART
	3. Can mobile phone technology improve adherence to care and treatment for HIV-infected TB patients?	3. Improved TB treatment success and better retention in HIV care and ART for co-infected patients

TB = tuberculosis; CPT = cotrimoxazole preventive therapy; ART = antiretroviral therapy; PLWH = people living with HIV/AIDS; ICF = intensified TB case finding; IPT = isoniazid preventive therapy; IC = infection control; LAM = lipoarabinomannan