Diagnostic and therapeutic biomarker responses in HIV and tuberculosis co-infected patients

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dc.contributor.advisorDheda, Keertan
dc.contributor.advisorTheron, Grant
dc.contributor.authorMthiyane, Thuli Carol Penelope
dc.date.accessioned2021-02-12T15:20:33Z
dc.date.available2021-02-12T15:20:33Z
dc.date.issued2020
dc.date.updated2021-02-12T15:19:56Z
dc.description.abstractIntroduction: Biomarkers of tuberculosis (TB) diagnosis and treatment response in patients coinfected with human immunodeficiency virus (HIV) are a necessity to ensure early diagnosis and adequate monitoring of TB treatment response. We conducted 3 sub-studies: study 1 was a bioavailability study; study 2 was a PK study in HIV-TB co-infected persons, and study 3 evaluated a WHO-recommended treatment algorithm in TB-HIV co-infected persons. Study 1 and 2 contributed to the study of 2 (NAT2) polymorphisms. Study 1 was leveraged to evaluate Quantiferon Gold in tube (QFT-GIT) and a quality of life instrument as a longitudinal biomarker in smear and culture positive TB-HIV co-infected patients. Study 3 was leveraged to study urine lipoarabinomannan (LAM) as a diagnostic adjunct in smear-negative HIV-infected patients treated for TB. Methods: Blood was collected from participants with HIV-infection only and TB-HIV coinfection for NAT2 polymorphisms at baseline, and for QFT-GIT at baseline, month 3, 6 and 12; a health-related quality-of-life (HRQOL) instrument was applied at the same timepoints to monitor treatment response in Study 1. An additional 40 TB-HIV co-infected participants (Study 2) were included in the analysis for the assessment of NAT2 polymorphisms and its effect on isoniazid plasma levels and hepatotoxicity. Urine was collected from seriously ill HIV-infected patients with confirmed smear-negative presumptive-TB (Study 3) prior to anti-TB treatment and tested using a commercially available LAM-ELISA. Blood and sputum were collected and processed for TB culture. Results: One hundred and twenty participants (100 TB-HIV co-infected and 20 non-TB but HIVinfected) from Study 1 and Study 2 with genotype results and were evaluated. Percentage of metabolisers in each category were: slow 52.5% (63/120), (NAT2*5/*5); intermediate 35.8% (43/120), (NAT2*4/*5 and NAT2*5/12); and rapid 11.7% (14/120), (NAT2*4/*11, NAT2*11/12 and NAT2*12/12). In general, isoniazid area under the concentration curve (AUC)0-∞ and maximum concentration (Cmax) were lower amongst the study 1 compared to study 2 participants. INH and AcINH PK parameters across genotypes were not statistically significantly different within each study. The log AcINH: log INH ratio, calculated as a measure of acetylation at two and four hours post-dose, showed no statistically significant difference between genotypes.
dc.identifier.apacitationMthiyane, T. C. P. (2020). <i>Diagnostic and therapeutic biomarker responses in HIV and tuberculosis co-infected patients</i>. (). ,Faculty of Health Sciences ,Department of Medicine. Retrieved from http://hdl.handle.net/11427/32846en_ZA
dc.identifier.chicagocitationMthiyane, Thuli Carol Penelope. <i>"Diagnostic and therapeutic biomarker responses in HIV and tuberculosis co-infected patients."</i> ., ,Faculty of Health Sciences ,Department of Medicine, 2020. http://hdl.handle.net/11427/32846en_ZA
dc.identifier.citationMthiyane, T.C.P. 2020. Diagnostic and therapeutic biomarker responses in HIV and tuberculosis co-infected patients. . ,Faculty of Health Sciences ,Department of Medicine. http://hdl.handle.net/11427/32846en_ZA
dc.identifier.ris TY - Doctoral Thesis AU - Mthiyane, Thuli Carol Penelope AB - Introduction: Biomarkers of tuberculosis (TB) diagnosis and treatment response in patients coinfected with human immunodeficiency virus (HIV) are a necessity to ensure early diagnosis and adequate monitoring of TB treatment response. We conducted 3 sub-studies: study 1 was a bioavailability study; study 2 was a PK study in HIV-TB co-infected persons, and study 3 evaluated a WHO-recommended treatment algorithm in TB-HIV co-infected persons. Study 1 and 2 contributed to the study of 2 (NAT2) polymorphisms. Study 1 was leveraged to evaluate Quantiferon Gold in tube (QFT-GIT) and a quality of life instrument as a longitudinal biomarker in smear and culture positive TB-HIV co-infected patients. Study 3 was leveraged to study urine lipoarabinomannan (LAM) as a diagnostic adjunct in smear-negative HIV-infected patients treated for TB. Methods: Blood was collected from participants with HIV-infection only and TB-HIV coinfection for NAT2 polymorphisms at baseline, and for QFT-GIT at baseline, month 3, 6 and 12; a health-related quality-of-life (HRQOL) instrument was applied at the same timepoints to monitor treatment response in Study 1. An additional 40 TB-HIV co-infected participants (Study 2) were included in the analysis for the assessment of NAT2 polymorphisms and its effect on isoniazid plasma levels and hepatotoxicity. Urine was collected from seriously ill HIV-infected patients with confirmed smear-negative presumptive-TB (Study 3) prior to anti-TB treatment and tested using a commercially available LAM-ELISA. Blood and sputum were collected and processed for TB culture. Results: One hundred and twenty participants (100 TB-HIV co-infected and 20 non-TB but HIVinfected) from Study 1 and Study 2 with genotype results and were evaluated. Percentage of metabolisers in each category were: slow 52.5% (63/120), (NAT2*5/*5); intermediate 35.8% (43/120), (NAT2*4/*5 and NAT2*5/12); and rapid 11.7% (14/120), (NAT2*4/*11, NAT2*11/12 and NAT2*12/12). In general, isoniazid area under the concentration curve (AUC)0-∞ and maximum concentration (Cmax) were lower amongst the study 1 compared to study 2 participants. INH and AcINH PK parameters across genotypes were not statistically significantly different within each study. The log AcINH: log INH ratio, calculated as a measure of acetylation at two and four hours post-dose, showed no statistically significant difference between genotypes. DA - 2020 DB - OpenUCT DP - University of Cape Town KW - HIV KW - tuberculosis co-infected patients KW - Biomarkers of tuberculosis LK - https://open.uct.ac.za PY - 2020 T1 - Diagnostic and therapeutic biomarker responses in HIV and tuberculosis co-infected patients TI - Diagnostic and therapeutic biomarker responses in HIV and tuberculosis co-infected patients UR - http://hdl.handle.net/11427/32846 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/32846
dc.identifier.vancouvercitationMthiyane TCP. Diagnostic and therapeutic biomarker responses in HIV and tuberculosis co-infected patients. []. ,Faculty of Health Sciences ,Department of Medicine, 2020 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/32846en_ZA
dc.language.rfc3066eng
dc.publisher.departmentDepartment of Medicine
dc.publisher.facultyFaculty of Health Sciences
dc.subjectHIV
dc.subjecttuberculosis co-infected patients
dc.subjectBiomarkers of tuberculosis
dc.titleDiagnostic and therapeutic biomarker responses in HIV and tuberculosis co-infected patients
dc.typeDoctoral Thesis
dc.type.qualificationlevelDoctoral
dc.type.qualificationlevelPhD
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