Abstract
Tuberculosis (TB) and cryptococcal meningitis are leading causes of morbidity and mortality in advanced HIV disease. Data are limited on TB co-infection among individuals with cryptococcal meningitis. We performed a retrospective analysis of HIV-infected participants with cryptococcal meningitis from 2010–2017. Baseline demographics were compared between three groups: ‘prevalent TB’ if TB treated >14 days prior to cryptococcal meningitis diagnosis, ‘concurrent TB’ if TB treated ± 14 days from diagnosis, or ‘No TB at baseline’. We used time-updated proportional-hazards regression models to assess TB diagnosis as a risk for death. Of 870 participants with cryptococcal meningitis, 50 (6%) had prevalent TB, 67 (8%) had concurrent TB, and 753 (86%) had no baseline TB. Among participants without baseline TB, 67 (9%) were diagnosed with incident TB (after >14 days), with a median time to TB incidence of 41 days (IQR, 22–69). The 18-week mortality was 50% (25/50) in prevalent TB, 46% (31/67) in concurrent TB, and 45% (341/753) in the no TB group (p = 0.81). However, TB co-infection was associated with an increased hazard of death (HR = 1.75; 95% CI, 1.33–2.32; p < 0.001) in a time-updated model. TB is commonly diagnosed in cryptococcal meningitis, and the increased mortality associated with co-infection is a public health concern.
Highlights
Tuberculosis (TB) and cryptococcal meningitis (CM) continue to be diseases of interest in the antiretroviral therapy (ART) era owing to their independent contribution to AIDS-related mortality, with TB alone contributing about 33% of the mortality in advanced HIV disease followed by cryptococcosis at 15% [1,2]
870 patients with HIV and a first episode of cryptococcal meningitis were enrolled into cryptococcal optimal ART timing (COAT) and ASTRO-CM clinical trials
We found among the TB prevalent group, only 60% had initiated ART at time of cryptococcal meningitis diagnosis, none had received cryptococcal antigen screening, and only 46% had a confirmed TB diagnosis
Summary
Tuberculosis (TB) and cryptococcal meningitis (CM) continue to be diseases of interest in the antiretroviral therapy (ART) era owing to their independent contribution to AIDS-related mortality, with TB alone contributing about 33% of the mortality in advanced HIV disease followed by cryptococcosis at 15% [1,2]. Autopsy studies in sub-Saharan Africa in hospitalized adults with HIV have attributed tuberculosis in 36%–47% of the patients and cryptococcosis in 12%–20% of the patients as the cause of death [3,4]. Wong et al found 62% of HIV-infected patients with Mycobacterium infection to have had multiple infectious causes of death at autopsy, including cryptococcosis [5]. The local host immune response is increasingly well described in each individual infection, a paucity of data exists regarding the immunology of co-infection. Both Cryptococcus and Mycobacterium tuberculosis are intracellular pathogens that induce a type 1 immune response marked by an interaction between cells of the adaptive immune response innate immune cells like macrophages and dendritic cells. HIV depletes both the number and functionality of all immune cells resulting in impaired immune responses and a predisposition toward disseminated tuberculosis and cryptococcosis
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