Blood and urine early treatment response biomarkers in HIV-associated disseminated tuberculosis

Background: Treatment response biomarkers are needed in the care of patients hospitalised with HIV-associated tuberculosis (TB). Objectives: We describe the changes in bacillary load during early treatment using quantitative and semi-quantitative measures of Mycobacterium tuberculosis in blood and urine. Method: We collected serial blood and urine samples at multiple timepoints in consenting adult patients with HIV and positive urine lipoarabinomannan (LAM), admitted to Mitchells Plain Hospital, Cape Town. Blood and urine Xpert Ultra, mycobacterial blood culture and urine LAM were performed. Survival analysis and mixed-effects modelling were used to determine time to a negative test, and to give the predicted probability of a positive test at the different timepoints. Results: Sixteen participants, predominantly male (63%), with median age 39 years (interquartile range [IQR] 36–43), and CD4 count 27 cells/mm3 (IQR 8–83) were included. At day 14, urine LAM, urine Xpert Ultra and blood Xpert Ultra remained positive in between 75% and 86% of the participants. A mixed-effects model predicted a decline in ordinal values of urine Xpert Ultra (cycle threshold), blood Xpert Ultra (cycle threshold) and blood culture (time-to-positivity) in response to anti-TB treatment. Conversely, urine LAM grade intensity increased over the 14 days. Conclusion: M. tuberculosis DNA was detectable in urine and blood in decreasing quantity up to 14 days of standard treatment in patients with HIV-associated TB. Urine Alere LAM showed an increasing grade intensity during this period. Further research in larger groups and extended periods are needed to assess relation to clinical outcomes.