Mycobacterium tuberculosis in Patients With HIV Carries Mortality Risk

A new study by investigators at the University of Liverpool’s Institute of Infection and Global Health, as well as colleagues in Africa, reveals that Mycobacterium tuberculosis carries a significant risk of mortality for patients with HIV and is often underdiagnosed. The study appeared in The Lancet.

The team conducted a review of studies that involved routine mycobacterial blood culture as well as a meta-analysis of individual patient data. Subjects analyzed were at least 13-year-old, HIV positive, had available CD4 counts, and experienced symptoms in accordance with the World Health Organization’s (WHO) definition of suspected tuberculosis. Nearly three-quarters of the patients (74%) were in sub-Saharan Africa.

The investigators employed mixed-effects modeling in order to predict the prevalence of M tuberculosis in this patient population, which was estimated at 45% in hospitalized HIV patients with tuberculosis and who had WHO-defined tuberculosis symptoms and a median CD4 count of 76 cells per uL. However, the diagnostic yield—or proportion—of positive patient sputum samples within the population of subjects infected with M tuberculosis was 77%, the investigators found. Once they added the results of urine lipoarabinomannan (LAM) testing, the diagnostic yield rose to 89%.

Looking at patient outcomes, it became clear to the study team that the presence of M tuberculosis was a significant predictor of mortality within 30 days of tuberculosis diagnosis, although there was no increased risk of death after 30 days. The team also found that subjects whose anti-tuberculosis treatment began more than 4 days after diagnosis had an increased mortality rate. Some patients may experience delays of 3 to 5 days before treatment is initiated, reflecting the WHO suggestion of an observation period should rapid testing not yield a diagnosis.

The investigators stressed that clinicians who rely solely on blood testing to diagnose tuberculosis and don’t take into account the results of sputum or urine testing are putting patients at a disadvantage. “Most settings with generalized HIV epidemics have no access to mycobacterial blood culture,” they wrote in their report. “Even where available, an average 3-week delay between culture and detection, combined with high early mortality, means that tuberculosis blood culture has limited diagnostic value.”

The study results show that M tuberculosis is a frequent presentation of the disease in people living with HIV who are hospitalized in lower-resource settings, with the infection generally underestimated. This has considerable implications for clinical treatment, the investigators said. Although rapid sputum testing is recommended by the WHO, the investigators suggest adding urine LAM testing as well to maximize the chance of an accurate result.

Regarding the WHO treatment algorithm of a 3- to 5-day delay in treatment initiation, the study’s authors warned that it puts vulnerable patients at risk. “Our study raises a concern that this delay is associated with an increase in early mortality,” they wrote. “Trials of presumptive tuberculosis therapy in people with HIV had negative results but recruited ambulant (without danger signs) outpatients, and so will have largely excluded patients with M tuberculosis BSI (bloodstream infection), in whom the benefit of early empirical therapy is most likely.”