Cohort profile of a study on outcomes related to tuberculosis and antiretroviral drug concentrations in Uganda: design, methods and patient characteristics of the SOUTH study

Abstract

PurposeTuberculosis (TB) is a leading cause of death among people living with HIV in sub-Saharan Africa. Several factors influence the efficacy of TB treatment by leading to suboptimal drug concentrations and subsequently affecting treatment outcome. The aim of this cohort is to determine the association between anti-TB drug concentrations and TB treatment outcomes.ParticipantsPatients diagnosed with new pulmonary TB at the integrated TB-HIV outpatient clinic in Kampala, Uganda, were enrolled into the study and started on first-line anti-TB treatment.Findings to dateBetween April 2013 and April 2015, the cohort enrolled 268 patients coinfected with TB/HIV; 57.8% are male with a median age of 34 years (IQR 29–40). The median time between the diagnosis of HIV and the diagnosis of TB is 2 months (IQR 0–22.5). The majority of the patients are antiretroviral therapy naive (75.4%). Our population is severely immunosuppressed with a median CD4 cell count at enrolment of 163 cells/µL (IQR 46–298). Ninety-nine per cent of the patients had a diagnosis of pulmonary TB confirmed by sputum microscopy, Xpert/RIF or culture and 203 (75.7%) have completed TB treatment with 5099 aliquots of blood collected for pharmacokinetic analysis.Future plansThis cohort provides a large database of well-characterised patients coinfected with TB/HIV which will facilitate the description of the association between serum drug concentrations and TB treatment outcomes as well as provide a research platform for future substudies including evaluation of virological outcomes.Trial registration numberNCT01782950; Pre-results.

Low Antituberculosis Drug Concentrations in HIV-Tuberculosis-Coinfected Adults with Low Body Weight: Is It Time To Update Dosing Guidelines?

“…Patients who had a glomerular filtration rate of Ͻ50 ml/min or elevated alanine aminotransferase levels Ͼ5 times the upper limit of normal (40 U/liter) or were pregnant were excluded from the study. Details concerning the methods of this study have been reported previously in a cohort profile of this study (2,30).…”

The Influence of Pharmacogenetic Variants in HIV/Tuberculosis Coinfected Patients in Uganda in the SOUTH Study

“…In this prospective observational study, the correlation of anti‐TB drug concentrations and clinical response in individuals infected with HIV with new pulmonary TB was investigated. The study was conducted at the Infectious Diseases Institute, Kampala, Uganda, a center of excellence in HIV care and treatment …”

“…The study was conducted at the Infectious Diseases Institute, Kampala, Uganda, a center of excellence in HIV care and treatment. 7,38 Ethics approval was received from the Joint Clinical and Research Centre Institutional Review Board, the Uganda National Council for Science and Technology, and the National Drug Authority. Written informed consent was obtained from all study participants prior to enrollment, and separate consent was obtained for pharmacogenetics study participation.…”

“…The complete SOUTH study protocol is detailed elsewhere. 38 Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study:…”

Comparison of Löwenstein–Jensen and BACTEC MGIT 960 culture for Mycobacterium tuberculosis in people living with HIV

“…Patients were enrolled in the Study on Outcomes Related to Tuberculosis and HIV Drug Concentrations in Uganda (SOUTH) (clinicaltrials.gov NCT01782950). Details of the study have been described elsewhere . This was a single‐centre prospective observational study in HIV/TB‐coinfected individuals exploring the correlation between TB treatment outcomes and anti‐TB drug exposure.…”