Blood and urine early treatment response biomarkers in HIV-associated disseminated tuberculosis
File(s) document (1).pdf (2.13 MB)
Published version
Author(s)
Type
Journal Article
Abstract
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.
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.
Date Issued
2025-04-09
Date Acceptance
2024-12-05
Citation
Southern African Journal of HIV Medicine, 2025, 26 (1)
ISSN
1608-9693
Publisher
AOSIS
Journal / Book Title
Southern African Journal of HIV Medicine
Volume
26
Issue
1
Copyright Statement
© 2025. The Authors. Licensee: AOSIS. This work is licensed under the Creative Commons Attribution License.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/40356939
PII: HIVMED-26-1664
Subjects
ADULTS
bacteraemia
biomarkers
CELLS
CONTACTS
DNA
HIV-associated tuberculosis
INFECTION
Infectious Diseases
Life Sciences & Biomedicine
lipoarabinomannan
LIPOARABINOMANNAN
PREVALENCE
RISK
Science & Technology
urine
Virology
WEIGHT-GAIN
Publication Status
Published
Coverage Spatial
South Africa
Article Number
a1664
Date Publish Online
2025-04-09
