Comparing rates of mycobacterial clearance in sputum smear-negative and smear-positive adults living with HIV
Abstract 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 HI...
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BMC
2021-05-01
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| Series: | BMC Infectious Diseases |
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| Online Access: | https://doi.org/10.1186/s12879-021-06133-4 |
| _version_ | 1818612367453323264 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Edith E. Machowski |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-16T15:45:06Z |
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| id | doaj.art-879276020bf045e9ade5f10bfaa38a9d |
| institution | Directory Open Access Journal |
| issn | 1471-2334 |
| language | English |
| last_indexed | 2024-12-16T15:45:06Z |
| publishDate | 2021-05-01 |
| publisher | BMC |
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| series | BMC Infectious Diseases |
| spelling | doaj.art-879276020bf045e9ade5f10bfaa38a9d2022-12-21T22:25:50ZengBMCBMC Infectious Diseases1471-23342021-05-012111710.1186/s12879-021-06133-4Comparing rates of mycobacterial clearance in sputum smear-negative and smear-positive adults living with HIVEdith E. Machowski0Matebogo Letutu1Limakatso Lebina2Ziyaad Waja3Reginah Msandiwa4Minja Milovanovic5Bhavna G. Gordhan6Kennedy Otwombe7Sven O. Friedrich8Richard Chaisson9Andreas H. Diacon10Bavesh Kana11Neil Martinson12Department of Science and Technology/National Research Foundation Centre of Excellence for Biomedical TB Research (CBTBR), University of the Witwatersrand, National Health Laboratory ServicePerinatal HIV Research Unit (PHRU), SAMRC Soweto Matlosana Collaborating Centre for HIV/AIDS and TB, Faculty of Health Sciences, University of the WitwatersrandPerinatal HIV Research Unit (PHRU), SAMRC Soweto Matlosana Collaborating Centre for HIV/AIDS and TB, Faculty of Health Sciences, University of the WitwatersrandPerinatal HIV Research Unit (PHRU), SAMRC Soweto Matlosana Collaborating Centre for HIV/AIDS and TB, Faculty of Health Sciences, University of the WitwatersrandPerinatal HIV Research Unit (PHRU), SAMRC Soweto Matlosana Collaborating Centre for HIV/AIDS and TB, Faculty of Health Sciences, University of the WitwatersrandPerinatal HIV Research Unit (PHRU), SAMRC Soweto Matlosana Collaborating Centre for HIV/AIDS and TB, Faculty of Health Sciences, University of the WitwatersrandDepartment of Science and Technology/National Research Foundation Centre of Excellence for Biomedical TB Research (CBTBR), University of the Witwatersrand, National Health Laboratory ServicePerinatal HIV Research Unit (PHRU), SAMRC Soweto Matlosana Collaborating Centre for HIV/AIDS and TB, Faculty of Health Sciences, University of the WitwatersrandTASK Applied Science, Bellville, Cape Town, South Africa and Pulmonology, Faculty of Medicine and Health Sciences, Stellenbosch UniversityJohns Hopkins University School of MedicineTASK Applied Science, Bellville, Cape Town, South Africa and Pulmonology, Faculty of Medicine and Health Sciences, Stellenbosch UniversityDepartment of Science and Technology/National Research Foundation Centre of Excellence for Biomedical TB Research (CBTBR), University of the Witwatersrand, National Health Laboratory ServiceDepartment of Science and Technology/National Research Foundation Centre of Excellence for Biomedical TB Research (CBTBR), University of the Witwatersrand, National Health Laboratory ServiceAbstract 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.https://doi.org/10.1186/s12879-021-06133-4TuberculosisHIVSmear microscopyXpert MTB/RIFMGITCulturability |
| spellingShingle | 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 Comparing rates of mycobacterial clearance in sputum smear-negative and smear-positive adults living with HIV BMC Infectious Diseases Tuberculosis HIV Smear microscopy Xpert MTB/RIF MGIT Culturability |
| title | Comparing rates of mycobacterial clearance in sputum smear-negative and smear-positive adults living with HIV |
| title_full | Comparing rates of mycobacterial clearance in sputum smear-negative and smear-positive adults living with HIV |
| title_fullStr | Comparing rates of mycobacterial clearance in sputum smear-negative and smear-positive adults living with HIV |
| title_full_unstemmed | Comparing rates of mycobacterial clearance in sputum smear-negative and smear-positive adults living with HIV |
| title_short | Comparing rates of mycobacterial clearance in sputum smear-negative and smear-positive adults living with HIV |
| title_sort | comparing rates of mycobacterial clearance in sputum smear negative and smear positive adults living with hiv |
| topic | Tuberculosis HIV Smear microscopy Xpert MTB/RIF MGIT Culturability |
| url | https://doi.org/10.1186/s12879-021-06133-4 |
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