The findings are of particular importance to health care providers in places where co-infections are common and resources are limited, such as Africa. Potentially, some of the biomarkers could be measured with a simple, currently available blood test that could help guide physicians on treatment strategies.
There are estimated to be over one million people worldwide who have TB and HIV co-infection, though the burden of disease through HIV/TB is particularly high in sub-Saharan Africa; it’s also becoming a growing concern in Asia. A recent study showed that up to 20 percent of patients died within 48 weeks, despite starting both ART and TB medications.
The prospective study of 201 patients in Botswana, who were evaluated pre and post ART, revealed that lower levels of eight biomarkers, including IL-6, IL-15 and GM-CSF, pre-ART were independently associated with an increased risk of IRIS, while higher levels of MCP-1 and TNF-alpha were independently associated with an increased risk of death. However, IRIS and early mortality patients both experienced rapid increases in immune activation and inflammation after initiating ART. Four biomarkers, including IL-6, TNF-alpha, and G-CSF, were independently associated with an increased risk of TB-IRIS, and five biomarkers were associated with an increased risk of death, including IL-1RA and G-CSF. The magnitude of early immune recovery (CD4 cell count) differed drastically between the two after being in ART, as well, underscoring the need for a personalized approach in these two groups. Those who initiated ART and died early had an increase in inflammation without the immune system rebounding enough to control the TB, while IRIS patients recovered more quickly. “The differences between the two groups, which haven’t been shown before, should influence future research in this vulnerable population, as interventions that seek to prevent IRIS could inadvertently be increasing the risk of death,” said Dr. Bisson. “In this population, it’s important to study treatments that can decrease inflammation while promoting functional immune recovery.” Co-authors of the study include Neo Tamuhla, Andrew P. Steenhoff, Rona Letlhogile, Kebatshabile Nfanyana, Scarlett L. Bellamy, Rob Roy MacGregor, Robert Gross, and Drew Weissman. The study was funded with grants award by the National Institutes of Health (NIAID R01AI080337) and the Center for AIDS Research (AI1045008.
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Lancet Infectious Diseases; Lancet Infectious Diseases