Addressing TB-related mortality in adults living with HIV: a review of the challenges and potential solutions

Abstract

Tuberculosis (TB) is the leading cause of death in people living with HIV (PLHIV) globally, causing 208,000 deaths in PLHIV in 2019. PLHIV have an 18-fold higher risk of TB, and HIV/TB mortality is highest in inpatient facilities, compared with primary care and community settings. Here we discuss challenges and potential mitigating solutions to address TB-related mortality in adults with HIV. Key factors that affect healthcare engagement are stigma, knowledge, and socioeconomic constraints, which are compounded in people with HIV/TB co-infection. Innovative approaches to improve healthcare engagement include optimizing HIV/TB care integration and interventions to reduce stigma. While early diagnosis of both HIV and TB can reduce mortality, barriers to early diagnosis of TB in PLHIV include difficulty producing sputum specimens, lower sensitivity of TB diagnostic tests in PLHIV, and higher rates of extra pulmonary TB. There is an urgent need to develop higher sensitivity biomarker-based tests that can be used for point-of-care diagnosis. Nonetheless, the implementation and scale-up of existing tests including molecular World Health Organization (WHO)-recommended diagnostic tests and urine lipoarabinomannan (LAM) should be optimized along with expanded TB screening with tools such as C-reactive protein and digital chest radiography. Decreased survival of PLHIV with TB disease is more likely with late HIV diagnosis and delayed start of antiretroviral (ART) treatment. The WHO now recommends starting ART within 2 weeks of initiating TB treatment in the majority of PLHIV, aside from those with TB meningitis. Dedicated TB treatment trials focused on PLHIV are needed, including interventions to improve TB meningitis outcomes given its high mortality, such as the use of intensified regimens using high-dose rifampin, new and repurposed drugs such as linezolid, and immunomodulatory therapy. Ultimately holistic, high-quality, person-centered care is needed for PLHIV with TB throughout the cascade of care, which should address biomedical, socioeconomic, and psychological barriers.

Predictors of death among TB/HIV co-infected patients on tuberculosis treatment in Sichuan, China: A retrospective cohort study

“…Ultimately, holistic, high-quality, person-centered care is needed for patients with TB/HIV coinfection throughout the cascade of care, which should address biomedical, socioeconomic, and psychological barriers. [30] Apart from these significant findings, our study had several limitations. First, because this study used an existing database, only limited demographic and clinical factors were included to explain the mortality risk among patients with TB/HIV coinfection.…”

“…Ultimately, holistic, high-quality, person-centered care is needed for patients with TB/HIV coinfection throughout the cascade of care, which should address biomedical, socioeconomic, and psychological barriers. [ 30 ]…”

Factors associated with mortality in HIV‐TB co‐infected patients during and after the course of TB treatment in high‐burden settings, Mumbai, India: A cohort analysis

“…Furthermore, due to monitoring of their laboratory parameters (such as CD4 counts and viral loads) and appropriate management of HIV disease, these individuals may, in general, have better immunological parameters. With the given difficulties in diagnosing TB among people with Advanced HIV disease, incorporation of WHO recommended point of care tests like Urine LF-LAM along with molecular diagnostic tests in the national diagnostic algorithm can help in rapid diagnosis of TB [32][33][34][35]. Low risk perception for TB and HIV infection among general population necessitates innovative public communication and advocacy strategies to raise awareness and implement active case finding activities among 'at risk' population in an integrated manner for early diagnosis of both the diseases.…”

Pulmonary tuberculosis risks and challenges

“…Tuberculosis is a contagious disease that commonly affects the lungs but can also affect other parts of the body. If left untreated, it can spread throughout the body and cause death [32]. The risk of acquiring PTB depends largely on a person's country of birth, with foreign-born individuals from high-burden countries being at highest [33].…”