TB remains the primary cause of AIDS-related morbidity and mortality worldwide, despite impressive scale up of antiretroviral treatment (ART). In 2019, TB was associated with an estimated 208 000 (30%) AIDS-related deaths (1). Global estimates show a 44% gap in case detection among people with HIVassociated TB (1). A systematic review of postmortem studies of global AIDS-related deaths in adults found TB to be the primary cause of death in 37.2% of cases (95% CI: 25.7–48.7). TB was undiagnosed prior to death in 45.8% of cases (95% CI: 32.6–59.1) (75). Ensuring early detection and timely treatment of TB among people living with HIV is of paramount importance for reducing mortality.
A key component of the HIV care cascade is the WHO-recommended four-symptom screen (W4SS) for adults and adolescents living with HIV, comprising screening for a current cough, fever, night sweats or weight loss. This has been the only WHO-recommended TB screening strategy for people living with HIV since its introduction in 2011, and it is recommended for use at every patient encounter with a health care worker (19). Designed primarily for ruling out active TB prior to the initiation of TPT, due to its high negative predictive value, the development of the W4SS was informed by a meta-analysis of individual patient data (IPD) from in observational studies conducted prior to 2010 and prior to the scale up of ART (76). However, a more recent systematic review found that the pooled sensitivity of the W4SS among people living with HIV who were on ART was 51% (95% CI: 28.4–73.2) and the specificity was 70.7% (95% CI: 47.7–86.4) (77). For people living with HIV who were not on ART, the sensitivity was 89.3% (95% CI: 82.6–93.9), and the specificity was 27.2% (95% CI: 17.3–40). In another study, the W4SS was found to have 42.9% sensitivity among pregnant women in Kenya attending services for prevention of mother to child transmission (78).
Therefore, a systematic literature review and meta-analysis of IPD was undertaken to assess further the accuracy of the W4SS among people living with HIV overall and within important subgroups and to identify other screening tools and strategies that would enhance TB detection among people living with HIV. Screening tools and strategies reviewed by the GDG included the use of C-reactive protein (CRP), CXR and mWRDs as stand-alone tests, as well as in combination with the W4SS. Culture was the reference standard for assessing the accuracy of the different screening strategies. These recommendations apply to adults and adolescents aged 10 years and older living with HIV; for recommendation on children under 10 years living with HIV see section 3.4.