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Scientists Identify Protein Biomarkers for Guiding Antiretroviral Therapy in AIDS Patients

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Researchers at the University of Minnesota and Makerere University in Kampala, Ugaunda, have discovered protein biomarkers that could potentially be used to identify AIDS patients with cryptococcal meningitis that are at risk of developing immune reconstitution inflammatory syndrome – IRIS – upon beginning HIV antiretroviral therapy.

IRIS is an exaggerated inflammatory response that can arise in response to antiretroviral therapy in AIDS patients with CM. It kills up to one-third of affected patients, complicating treatment of this cohort. Currently, doctors are unable to predict which individuals will develop IRIS when given HIV therapy.

The study, which was detailed in a paper published this week in PLoS Medicine, examined 101 Ugandan AIDS patients with recent CM, comparing protein levels of those individuals who did and did not go on to develop IRIS. Those who developed IRIS after starting antiretroviral therapy initially had four-fold higher baseline levels of cryptococcal antigen in their blood and showed increased expression of the proteins IL-4 and IL-17 along with decreased expression of the proinflammatory cytokines TNF-α, G-CSF, GM-CSF, and VEGF. Using an algorithm based on those seven analytes, the researchers were able to stratify patients as either high-, moderate-, or low-risk for progression to IRIS.

The team also identified several protein markers that could be useful in monitoring the status of patients who have begun antiretroviral therapy, tying increased levels of C-reactive protein, D-dimer, IL-6, IL-7, IL-13, G-CSF, and IL-1RA to increased risk of IRIS.

CM is the most common central nervous system disease in AIDS patients and is responsible for an estimated 20 percent to 40 percent of AIDS-attributable deaths in Africa. If validated, the markers identified in the study could be useful tools for stratifying risk of CM-IRIS and better guiding clinical decisions regarding antiretroviral treatment.

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