Immune biomarkers help predict early death, complications in HIV patients with TB

Doctors treating patients battling both HIV and tuberculosis (TB)—many of whom live in Africa—are faced with the decision when to start those patients on antiretroviral therapy (ART) while they are being treated with antibiotics for active TB disease. Some patients fare well on both interventions, with the immune system in check and the TB controlled. Others undergo complications from TB, such as paradoxical immune reconstitution inflammatory syndrome (IRIS), a worsening of TB symptoms despite response to therapy, while still others experience immune failure and early death. The best way to determine which patients go on to develop IRIS or die after treatment begins is not fully understood.

Now, reporting in a new study published online this week in The Lancet Infectious Diseases, researchers have identified immune biomarkers in patients before they begin ART that could help distinguish these two groups.

The findings are of particular importance to healthcare 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.

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.