Comparing rates of mycobacterial clearance in sputum smear-negative and smear-positive adults living with HIV

Edith E. Machowski, Matebogo Letutu, Limakatso Lebina, Ziyaad Waja, Reginah Msandiwa, Minja Milovanovic, Bhavna G. Gordhan, Kennedy Otwombe, Sven O. Friedrich, Richard Chaisson, Andreas H. Diacon, Bavesh Kana, Neil Martinson

Research output: Contribution to journalArticlepeer-review


Background: Pulmonary tuberculosis (TB) in people living with HIV (PLH) frequently presents as sputum smear-negative. 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.

Original languageEnglish (US)
Article number466
JournalBMC infectious diseases
Issue number1
StatePublished - Dec 2021


  • Bacterial load
  • Culturability
  • HIV
  • MGIT
  • Smear microscopy
  • Tuberculosis
  • Xpert MTB/RIF

ASJC Scopus subject areas

  • Infectious Diseases


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