Comparing rates of mycobacterial clearance in sputum smear-negative and smear-positive adults living with HIV
Date
2021-05-22
Journal Title
Journal ISSN
Volume Title
Publisher
BMC (part of Springer Nature)
Abstract
Background: Pulmonary tuberculosis (TB) in people living with HIV (PLH) frequently presents as sputum smearnegative.
However, clinical trials of TB in adults often use smear-positive individuals to ensure measurable bacterial
responses following initiation of treatment, thereby excluding HIV-infected patients from trials.
Methods: In this prospective case cohort study, 118 HIV-seropositive TB patients were assessed prior to initiation of
standard four-drug TB therapy and at several time points through 35 days. Sputum bacillary load, as a marker of
treatment response, was determined serially by: smear microscopy, Xpert MTB/RIF, liquid culture, and colony counts
on agar medium.
Results: By all four measures, patients who were baseline smear-positive had higher bacterial loads than those
presenting as smear-negative, until day 35. However, most smear-negative PLH had significant bacillary load at
enrolment and their mycobacteria were cleared more rapidly than smear-positive patients. Smear-negative patients’
decline in bacillary load, determined by colony counts, was linear to day 7 suggesting measurable bactericidal
activity. Moreover, the decrease in bacterial counts was comparable to smear-positive individuals. Increasing cycle
threshold values (Ct) on the Xpert assay in smear-positive patients to day 14 implied decreasing bacterial load.
Conclusion: Our data suggest that smear-negative PLH can be included in clinical trials of novel treatment
regimens as they contain sufficient viable bacteria, but allowances for late exclusions would have to be made in
sample size estimations. We also show that increases in Ct in smear-positive patients to day 14 reflect treatment
responses and the Xpert MTB/RIF assay could be used as biomarker for early treatment response.
Description
CITATION: Machowski, E. E., et al. 2021. Comparing rates of mycobacterial clearance in sputum smear-negative and smear-positive adults living with HIV. BMC Infectious Diseases, 21:466, doi:10.1186/s12879-021-06133-4.
The original publication is available at https://bmcinfectdis.biomedcentral.com
The original publication is available at https://bmcinfectdis.biomedcentral.com
Keywords
Tuberculosis
Citation
Machowski, E. E., et al. 2021. Comparing rates of mycobacterial clearance in sputum smear-negative and smear-positive adults living with HIV. BMC Infectious Diseases, 21:466, doi:10.1186/s12879-021-06133-4