Project Details
Layman's description
The introduction of bedaquiline revolutionised the treatment of rifampicin-resistant tuberculosis (Rr-TB). Bedaquiline is the most potent second-line drug currently available and allows for the shortening of Rr-TB treatment to 6 months. All short-course regimens for Rr-TB rely on BDQ as a core drug. However, resistance to bedaquiline is a growing problem globally, causing recurrent Rr-TB, a new episode of active Rr-TB after an unsuccessful bedaquiline-based Rr-TB treatment, for which treatment options are dire.
Treatment interruptions of TB treatment regimens, including bedaquiline-based regimens, are common and likely increase the risk of acquired resistance to bedaquiline, especially if this occurs before culture conversion. Bedaquiline has a half-life of 5.5 months and remains in the body after other drugs have been eliminated, which leads to “functional monotherapy” and may induce acquired drug resistance. The relationship between duration of treatment interruptions and acquired resistance to bedaquiline in persons with Rr-TB recurrence is yet to be studied.
The first study of my PhD project is a scoping review on the characteristics and management of persons with recurrent Rr-TB. I will be the first to summarise existing evidence on types of Rr-TB recurrence (after failure, relapse, or loss to follow-up), the resistance profile at the start of Rr-TB re-treatment, regimens used for Rr-TB re-treatment, and treatment outcomes. This study will provide information that will aid in the guidance of re-treatment strategies for Rr-TB.
My second study is a prospective cohort study to estimate the frequency of Rr-TB recurrence and describe acquired drug resistance after short bedaquiline-containing regimens in Nigeria. This study will enhance the understanding of the burden of TB recurrence and, in turn, inform strategies to control the transmission of highly resistant strains of TB.
My third study is a prospective observational study to identify recurrent Rr-TB in persons previously enrolled on a bedaquiline-based 6-month Rr-TB treatment regimen. I will be the first to investigate the association between interruptions and recurrence with acquired drug resistance to bedaquiline and other drugs of the previously unsuccessful Rr-TB treatment regimen. Indeed, treatment interruptions, including lost to follow-up, have increased in Nigeria even after the introduction of shorter regimens. Examining how the duration of treatment interruptions is associated with acquired drug resistance will inform strategies to protect the longevity of these drugs.
My fourth study, a qualitative research study, will explore the reasons for treatment interruptions, the barriers to care and how stakeholders (including persons with Rr-TB on BPaLM or Rr-TB re-treatment who interrupted treatment or were lost to follow-up, their treatment supporters, community-based organisations supporting treatment and healthcare givers) perceive the implications of treatment interruptions on acquired resistance and future treatment options. The study will inform strategies to prevent interruptions, including loss to follow-up, in Nigeria.
Treatment interruptions of TB treatment regimens, including bedaquiline-based regimens, are common and likely increase the risk of acquired resistance to bedaquiline, especially if this occurs before culture conversion. Bedaquiline has a half-life of 5.5 months and remains in the body after other drugs have been eliminated, which leads to “functional monotherapy” and may induce acquired drug resistance. The relationship between duration of treatment interruptions and acquired resistance to bedaquiline in persons with Rr-TB recurrence is yet to be studied.
The first study of my PhD project is a scoping review on the characteristics and management of persons with recurrent Rr-TB. I will be the first to summarise existing evidence on types of Rr-TB recurrence (after failure, relapse, or loss to follow-up), the resistance profile at the start of Rr-TB re-treatment, regimens used for Rr-TB re-treatment, and treatment outcomes. This study will provide information that will aid in the guidance of re-treatment strategies for Rr-TB.
My second study is a prospective cohort study to estimate the frequency of Rr-TB recurrence and describe acquired drug resistance after short bedaquiline-containing regimens in Nigeria. This study will enhance the understanding of the burden of TB recurrence and, in turn, inform strategies to control the transmission of highly resistant strains of TB.
My third study is a prospective observational study to identify recurrent Rr-TB in persons previously enrolled on a bedaquiline-based 6-month Rr-TB treatment regimen. I will be the first to investigate the association between interruptions and recurrence with acquired drug resistance to bedaquiline and other drugs of the previously unsuccessful Rr-TB treatment regimen. Indeed, treatment interruptions, including lost to follow-up, have increased in Nigeria even after the introduction of shorter regimens. Examining how the duration of treatment interruptions is associated with acquired drug resistance will inform strategies to protect the longevity of these drugs.
My fourth study, a qualitative research study, will explore the reasons for treatment interruptions, the barriers to care and how stakeholders (including persons with Rr-TB on BPaLM or Rr-TB re-treatment who interrupted treatment or were lost to follow-up, their treatment supporters, community-based organisations supporting treatment and healthcare givers) perceive the implications of treatment interruptions on acquired resistance and future treatment options. The study will inform strategies to prevent interruptions, including loss to follow-up, in Nigeria.
| Status | Active |
|---|---|
| Effective start/end date | 1/01/26 → … |
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