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

BMC Infectious Diseases

Edith E. Machowski¹  Bavesh Kana¹  Bhavna G. Gordhan¹  Neil Martinson²  Richard Chaisson³  Ziyaad Waja⁴  Reginah Msandiwa⁴  Matebogo Letutu⁴  Limakatso Lebina⁴  Minja Milovanovic⁴  Kennedy Otwombe⁵  Sven O. Friedrich⁶  Andreas H. Diacon⁶ 

[1] Department of Science and Technology/National Research Foundation Centre of Excellence for Biomedical TB Research (CBTBR), University of the Witwatersrand, National Health Laboratory Service, Johannesburg, South Africa;Department of Science and Technology/National Research Foundation Centre of Excellence for Biomedical TB Research (CBTBR), University of the Witwatersrand, National Health Laboratory Service, Johannesburg, South Africa;Perinatal HIV Research Unit (PHRU), SAMRC Soweto Matlosana Collaborating Centre for HIV/AIDS and TB, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa;Johns Hopkins University School of Medicine, Baltimore, MD, USA;Johns Hopkins University School of Medicine, Baltimore, MD, USA;Perinatal HIV Research Unit (PHRU), SAMRC Soweto Matlosana Collaborating Centre for HIV/AIDS and TB, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa;Perinatal HIV Research Unit (PHRU), SAMRC Soweto Matlosana Collaborating Centre for HIV/AIDS and TB, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa;School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa;TASK Applied Science, Bellville, Cape Town, South Africa and Pulmonology, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa;

关键词: Tuberculosis;    HIV;    Smear microscopy;    Xpert MTB/RIF;    MGIT;    Culturability;    Bacterial load;   

DOI  :  10.1186/s12879-021-06133-4

来源: Springer

【 摘 要 】

BackgroundPulmonary 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.MethodsIn 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.ResultsBy 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.ConclusionOur 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.

【 授权许可】

CC BY