The changing landscape of diagnosing HIV-associated tuberculosis

Tuberculosis is the most common cause of hospitalisation and death globally among people with HIV (PWH), even in the antiretroviral therapy era. Diagnosis of tuberculosis is challenging in PWH as bacillary load is lower in sputum and a high proportion have extrapulmonary or disseminated tuberculosis. The clinical features of tuberculosis in PWH are nonspecific and there is a wide differential diagnosis of other opportunistic infections. Tuberculosis progresses rapidly in people with advanced HIV disease, necessitating rapid diagnosis. In this narrative review, key changes are described in the diagnosis of HIV-associated tuberculosis in adults from 1990 until the present. Smear microscopy was the only rapid diagnostic test for tuberculosis until 2011, but its sensitivity is lower in PWH. Algorithms for diagnosing smear-negative tuberculosis had poor diagnostic accuracy, resulting in both underdiagnosis, which increased tuberculosis deaths, and overdiagnosis, leading to missed or delayed diagnosis of the opportunistic infections causing the symptoms. The evidence base for screening for HIV-associated tuberculosis is strong among ambulatory PWH, but screening algorithms have lower sensitivity in people on antiretroviral therapy. The development of novel rapid diagnostic tests (nucleic acid amplification tests and urine lipoarabinomannan lateral flow assay) for tuberculosis and the advent of antiretroviral therapy have dramatically changed the landscape of diagnosing HIV- associated tuberculosis, resulting in reductions in both tuberculosis incidence and deaths. Diagnostic challenges persist as none of the currently available rapid diagnostic tests have sensitivities that are ideal, and only one test (urine lipoarabinomannan detection) is both affordable and simple to perform at the point of care. Therefore, there is still a need for the development of novel, accurate and affordable point-of-care tests to improve the rapid diagnosis of HIV-associated tuberculosis.