Improving the prevention, diagnosis and treatment of TB among people living with HIV: the role of operational research

Abstract

Operational research is necessary to improve the access to and delivery of tuberculosis prevention, diagnosis and treatment interventions for people living with HIV. We conducted an extensive review of the literature and reports from recent expert consultations and research-related meetings organized by the World Health Organization and the Stop TB Partnership to identify a TB/HIV operational research agenda. We present critical operational research questions in a series of key areas: optimizing TB prevention by enhancing the uptake of isoniazid preventive therapy and the implementation of infection control measures; assessing the effectiveness of existing diagnostic tools and scaling up new technologies; improving service delivery models; and reducing risk factors for mortality among TB patients living with HIV. We discuss the potential impact that addressing the operational research questions may have on improving programmes' performance, assessing new strategies or interventions for TB control, or informing global or national policy formulation. Financial resources to implement these operational research questions should be mobilized from existing and new funding mechanisms. National TB and HIV/AIDS programmes should develop their operational research agendas based on these questions, and conduct the research that they consider crucial for improving TB and HIV control in their settings in collaboration with research stakeholders.

Figure 1

Algorithm for the diagnosis of tuberculosis in ambulatory HIV-positive patients using Xpert MTB/RIF.¹Among adults and adolescents living with HIV, a TB suspect is defined as a person who reports any one of current cough, fever, weight loss or night sweats. Among children living with HIV, a TB suspect is defined as a person who reports one of poor weight gain, fever, current cough, or history of contact with a TB case. ²In all persons with unknown HIV status, HIV testing should be performed according to national guidelines. In patients who are HIV negative or remain HIV unknown (e.g., refusal), a TB suspect is defined according to national case definitions. A person with unknown HIV status can still be classified as HIV-positive if there is strong clinical evidence of HIV infection. ³The danger signs include any one of: respiratory rate >30/min, temperature >39°C, heart rate >120/min and unable to walk unaided. ⁴CPT = cotrimoxazole preventive therapy. ⁵ART = antiretroviral therapy. All TB patients living with HIV are eligible for ART irrespective of CD4 count. Start TB treatment first, followed by ART as soon as possible within the first 8 weeks of TB treatment. See ART guidelines. ⁶In low MDR-TB prevalence settings, a confirmatory test for rifampicin resistance should be performed. See MDR-TB Xpert MTB/RIF algorithm. ⁷A chest x-ray can assist with the diagnosis of extra-pulmonary TB (e.g., pleural, pericardial) and help assess for other etiologies of respiratory illness. It should only be performed in those settings where the quality of the film and its interpretation are assured. ⁸Antibiotics (except fluoroquinolones) to cover both typical and atypical bacteria should be considered. ⁹An HIV treatment assessment includes WHO clinical staging and/or CD4 count to assess eligibility for antiretroviral therapy. See ART guidelines. ¹⁰PCP= Pneumocystis jirovecii pneumonia.

Figure 2

Algorithm for the diagnosis of tuberculosis in seriously ill HIV-positive patients using Xpert.¹Seriously ill refers to the presence of danger signs, including: respiratory rate >30/min, temperature >39°C, heart rate >120/min and unable to walk unaided. ²Among adults and adolescents living with HIV, a TB suspect is defined as a person who reports any one of current cough, fever, weight loss or night sweats. Among children living with HIV, a TB suspect is defined as a person who reports one of poor weight gain, fever, current cough, or history of contact with a TB case. ³In all persons with unknown HIV status, HIV testing should be performed according to national guidelines. In high HIV prevalent settings, seriously ill patients should be tested using Xpert MTB/RIF as the primary diagnostic test regardless of HIV status. ⁴The highest priority should be to provide the patient with life-sustaining supportive therapy, such as oxygen and parenteral antibiotics. If life-sustaining therapy is not available at the initial point of care, the patient should be transferred immediately to a higher level facility before further diagnostic testing. ⁵Antibiotics (except fluoroquinolones) to cover both typical and atypical bacteria should be considered. ⁶PCP= Pneumocystis jirovecii pneumonia. ⁷CPT = cotrimoxazole preventive therapy. ⁸ART = antiretroviral therapy. All TB patients living with HIV are eligible for ART irrespective of CD4 count. Start TB treatment first, followed by ART as soon as possible within the first 8 weeks of TB treatment. See ART guidelines. ⁹In low MDR-TB prevalence setting, a confirmatory test for Rifampicin resistance should be performed. See MDR-TB algorithm. ¹⁰An HIV treatment assessment includes WHO clinical staging and/or CD4 count to assess eligibility for antiretroviral therapy. See ART guidelines. ¹¹Additional investigations for TB may include chest x-ray, liquid culture of sputum, lymph node aspiration for acid-fast bacilli microscopy and culture, abdominal ultrasound. Non-tuberculosis mycobacterial infection should be considered in the differential diagnosis of patients who have a negative Xpert but a sputum or extra-pulmonary specimen with acid-fast bacilli.