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Dr Christine Sekaggya-Wiltshire

Call Career Development Fellowship (CDF)
Programme EDCTP2
Start Date 2018-06-01
End Date 2021-11-30
Project Code TMA2016CDF1580
Status Completed

Title

Safety and Efficacy of High Dose Rifampicin in TB-HIV co-infected patients on Efavirenz-based Antiretroviral therapy

Objectives

Primary objective 1. To determine the effect of a high dose of rifampicin (35 mg/kg orally) on the pharmacokinetics of first-line antiretroviral drugs (efavirenz and dolutegravir) in TB-HIV co-infected patients on TB treatment. Secondary objectives 1. To investigate the safety/tolerability of a high dose of rifampicin in TB-HIV co-infected patients on TB treatment and first-line antiretroviral therapies. 2. To determine if TB-HIV co-infected patients on a high dose of rifampicin are more likely to have negative sputum cultures by the end of the intensive phase of TB treatment than patients on standard-dose rifampicin. 3. To explore the relationships between exposure to rifampicin, efavirenz and dolutegravir and the tolerability and efficacy of these drugs.

Host Organisation

Institution Country
Makerere University - IDI Uganda

Study Design

Randomized four-arm open label clinical trial (Phase IIb) High dose rifampicin will be administered for the first 8 weeks (intensive phase) of TB treatment. All other anti-TB drugs will be administered at the standard dose using fixed-dose combinations (FDC). All participants will receive standard dose rifampicin during the continuation phase (weeks 9 -24)

Phd Study

Title University Start Date End Date
Correlating rifampcin and isoniazid concentrations with treatment outcomes in TB/HIV co-infected patients Makerere University/University of Zurich 2015-07-15 2019-05-05

Results & Outcomes

Sub-therapeutic rifampicin and isoniazid concentrations in up to 84% of population which was associated with delayed sputum conversion No association between drug concentrations and sputum smear conversion is not surprising Efavirenz associated with 20% increase in isoniazid clearance

Publications

PMC7020342

Current Organisation

Infectious Diseases Institute

Current Job Title

Post-doc researcher

Awards

2018 Stephen Lawn Research TB-HIV Research Leadership Award

Education

Institution Degree Year
Makerere University, Uganda MBChB 2006-06-01
Makerere University, Uganda Masters in Internal Medicine 2012-07-01
Makerere University/University of Zurich, Uganda PHD 2018-09-01

Areas Of Specialisation

Human Immuno-deficiency Virus (HIV) Tuberculosis (TB)

Grants

Innovation to Ensure Safe and Effective TB Treatment in Africa/ Tuberculosis in COVID times
Grant Code:
Source of funding:
Amount:
130000
Role:
Co-Principal Investigator
Start Date:
2018-01-01
End Date:
2021-01-01
Pharmacogentic guided dosing for Isoniazid among TB-HIV con-infected patients
Grant Code:
Source of funding:
Amount:
62000
Role:
Principal Investigator
Start Date:
2020-01-01
End Date:
2021-01-01
Engaging private sector in the diagnosis of tuberculosis to increase case detection
Grant Code:
Source of funding:
Amount:
275000
Role:
Principal Investigator
Start Date:
2019-01-01
End Date:
2021-01-01
Engaging private sector in the diagnosis of tuberculosis to increase case detection
Grant Code:
Source of funding:
Amount:
400000
Role:
Co-Principal Investigator
Start Date:
2019-01-01
End Date:
2022-01-01
Clinical Predictors of weekly Rifapentine/isoniazid related adverse drug reactions during national roll-out of tuberculosis preventive therapy
Grant Code:
Source of funding:
NIH
Amount:
670000
Role:
Principal Investigator
Start Date:
2021-01-01
End Date:
2025-01-01
Preparation for Randomised Evaluation of a Vitamin C bundle for Sepsis Treatment in Africa
Grant Code:
Source of funding:
MRC
Amount:
149000
Role:
Co-Investigator
Start Date:
2020-01-01
End Date:
2021-01-01
Utility of Urine LAM for TB treatment response monitoring
Grant Code:
Source of funding:
NURTURE
Amount:
42000
Role:
Principal Investigator
Start Date:
2019-01-01
End Date:
2020-01-01

Publications

Sustained positive impact on tuberculosis treatment outcomes of TB-HIV integrated care in Uganda.
Authors:
Musaazi J , author
Sekaggya-Wiltshire C , author
Kiragga AN , author
Kalule I , author
Reynolds SJ , author
Manabe YC , author
Castelnuovo B , author
Date:
2019-04-01
Journal:
The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease
Content:
Identifiers:
PMID: 31064632
DOI: 10.5588/ijtld.18.0306
Anti-TB drug concentrations and drug-associated toxicities among TB/HIV-coinfected patients.
Authors:
Sekaggya-Wiltshire C , author
von Braun A , author
Scherrer AU , author
Manabe YC , author
Buzibye A , author
Muller D , author
Ledergerber B , author
Gutteck U , author
Corti N , author
Kambugu A , author
Byakika-Kibwika P , author
Kamya MR , author
Date:
2017-04-01
Journal:
The Journal of antimicrobial chemotherapy
Content:
Identifiers:
PMID: 28108678
PMC: PMC5703350
DOI: 10.1093/jac/dkw534
Low isoniazid and rifampicin concentrations in TB/HIV co-infected patients in Uganda.
Authors:
Wiltshire CS , author
Lamorde M , author
Scherrer A , author
Musaazi J , author
Corti N , author
Allan B , author
Nakijoba R , author
Nalwanga D , author
Henning L , author
Von Braun A , author
Okware S , author
Castelnuovo B , author
Kambugu A , author
Fehr J , author
Date:
2014-11-01
Journal:
Journal of the International AIDS Society
Content:
Identifiers:
PMID: 25394091
PMC: PMC4224868
DOI: 10.7448/IAS.17.4.19585
Early virological failure and HIV drug resistance in Ugandan adults co-infected with tuberculosis.
Authors:
von Braun A , author
Sekaggya-Wiltshire C , author
Scherrer AU , author
Magambo B , author
Kambugu A , author
Fehr J , author
Castelnuovo B , author
Date:
2017-01-01
Journal:
AIDS research and therapy
Content:
Identifiers:
PMID: 28086929
PMC: PMC5237283
DOI: 10.1186/s12981-016-0128-5
Comparison of Löwenstein-Jensen and BACTEC MGIT 960 culture for Mycobacterium tuberculosis in people living with HIV.
Authors:
Hongler J , author
Musaazi J , author
Ledergerber B , author
Eberhard N , author
Sekaggya-Wiltshire C , author
Keller PM , author
Fehr J , author
Castelnuovo B , author
Date:
2018-07-01
Journal:
HIV medicine
Content:
Identifiers:
PMID: 29971898
DOI: 10.1111/hiv.12635
Antiretroviral concentration measurements as an additional tool to manage virologic failure in resource limited settings: a case control study.
Authors:
Buzibye A , author
Musaazi J , author
von Braun A , author
Nanzigu S , author
Sekaggya-Wiltshire C , author
Kambugu A , author
Fehr J , author
Lamorde M , author
Gutteck U , author
Muller D , author
Sowinski S , author
Reynolds SJ , author
Castelnuovo B , author
Date:
2019-12-01
Journal:
AIDS research and therapy
Content:
Identifiers:
PMID: 31810468
PMC: PMC6898957
DOI: 10.1186/s12981-019-0255-x
High efavirenz serum concentrations in TB/HIV-coinfected Ugandan adults with a CYP2B6 516 TT genotype on anti-TB treatment.
Authors:
von Braun A , author
Castelnuovo B , author
Ledergerber B , author
Cusato J , author
Buzibye A , author
Kambugu A , author
Fehr J , author
Calcagno A , author
Lamorde M , author
Sekaggya-Wiltshire C , author
Date:
2019-01-01
Journal:
The Journal of antimicrobial chemotherapy
Content:
Identifiers:
PMID: 30239753
DOI: 10.1093/jac/dky379
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.
Authors:
Sekaggya-Wiltshire C , author
Castelnuovo B , author
von Braun A , author
Musaazi J , author
Muller D , author
Buzibye A , author
Gutteck U , author
Henning L , author
Ledergerber B , author
Corti N , author
Lamorde M , author
Fehr J , author
Kambugu A , author
Date:
2017-09-01
Journal:
BMJ open
Content:
Identifiers:
PMID: 28928173
PMC: PMC5623357
DOI: 10.1136/bmjopen-2016-014679
Detection of tuberculosis patterns in digital photographs of chest X-ray images using Deep Learning: feasibility study.
Authors:
Becker AS , author
Blüthgen C , author
Phi van VD , author
Sekaggya-Wiltshire C , author
Castelnuovo B , author
Kambugu A , author
Fehr J , author
Frauenfelder T , author
Date:
2018-03-01
Journal:
The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease
Content:
Identifiers:
PMID: 29471912
DOI: 10.5588/ijtld.17.0520
Ten years of antiretroviral therapy: Incidences, patterns and risk factors of opportunistic infections in an urban Ugandan cohort.
Authors:
Weissberg D , author
Mubiru F , author
Kambugu A , author
Fehr J , author
Kiragga A , author
von Braun A , author
Baumann A , author
Kaelin M , author
Sekaggya-Wiltshire C , author
Kamya M , author
Castelnuovo B , author
Date:
2018-11-01
Journal:
PloS one
Content:
Identifiers:
PMID: 30383836
PMC: PMC6211746
DOI: 10.1371/journal.pone.0206796
A Lower Dose of Efavirenz Can Be Coadministered With Rifampicin and Isoniazid in Tuberculosis Patients.
Authors:
Kaboggoza JP , author
Wang X , author
Neary M , author
Ayuso P , author
Sekaggya-Wiltshire C , author
Nakalema S , author
Owen A , author
McClure M , author
Lamorde M , author
Boffito M , author
Date:
2019-01-01
Journal:
Open Forum Infectious Diseases
Content:
Identifiers:
PMID: 30815503
PMC: PMC6386798
DOI: 10.1093/ofid/ofz035
Virological Outcome of Patients With HIV Drug Resistance Attending an Urban Outpatient Clinic in Uganda: A Need for Structured Adherence Counseling and Third-Line Treatment Options.
Authors:
Baumann A , author
Musaazi J , author
Kambugu A , author
Kälin M , author
Weissberg D , author
Ssemwanga D , author
Fehr J , author
Castelnuovo B , author
Sekaggya-Wiltshire C , author
von Braun A , author
Date:
2019-04-01
Journal:
Journal of acquired immune deficiency syndromes (1999)
Content:
Identifiers:
PMID: 30633041
DOI: 10.1097/qai.0000000000001943
The utility of pharmacokinetic studies for the evaluation of exposure-response relationships for standard dose anti-tuberculosis drugs.
Authors:
Sekaggya-Wiltshire C , author
Lamorde M , author
Kiragga AN , author
Dooley KE , author
Kamya MR , author
Kambugu A , author
Fehr J , author
Manabe YC , author
Castelnuovo B , author
Date:
2017-11-01
Journal:
Tuberculosis (Edinburgh, Scotland)
Content:
Identifiers:
PMID: 29523331
PMC: PMC5846119
DOI: 10.1016/j.tube.2017.11.004
Increasing retention of HIV positive pregnant and breastfeeding mothers on option-b plus by upgrading and providing full time HIV services at a lower health facility in rural Uganda.
Authors:
Masereka EM , author
Ngabirano TD , author
Osingada CP , author
Wiltshire CS , author
Castelnuovo B , author
Kiragga AN , author
Date:
2019-07-01
Journal:
BMC public health
Content:
Identifiers:
PMID: 31307455
PMC: PMC6631982
DOI: 10.1186/s12889-019-7280-5
International Congress of Drug Therapy in HIV Infection 23-26 October 2016, Glasgow, UK.
Authors:
Date:
2016-10-01
Journal:
Journal of the International AIDS Society
Content:
Identifiers:
PMID: 27780519
PMC: PMC5080528
DOI: 10.7448/IAS.19.8.21487
Treatment decisions and mortality in HIV-positive presumptive smear-negative TB in the Xpert™ MTB/RIF era: a cohort study.
Authors:
Hermans SM , author
Babirye JA , author
Mbabazi O , author
Kakooza F , author
Colebunders R , author
Castelnuovo B , author
Sekaggya-Wiltshire C , author
Parkes-Ratanshi R , author
Manabe YC , author
Date:
2017-06-01
Journal:
BMC infectious diseases
Content:
Identifiers:
PMID: 28622763
PMC: PMC5473987
DOI: 10.1186/s12879-017-2534-2
Delayed Sputum Culture Conversion in Tuberculosis-Human Immunodeficiency Virus-Coinfected Patients With Low Isoniazid and Rifampicin Concentrations.
Authors:
Sekaggya-Wiltshire C , author
von Braun A , author
Lamorde M , author
Ledergerber B , author
Buzibye A , author
Henning L , author
Musaazi J , author
Gutteck U , author
Denti P , author
de Kock M , author
Jetter A , author
Fehr JS , author
Date:
2018-08-01
Journal:
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Content:
Identifiers:
PMID: 29514175
PMC: PMC6094003
DOI: 10.1093/cid/ciy179
Importance of routine viral load monitoring: higher levels of resistance at ART failure in Uganda and Lesotho compared with Switzerland.
Authors:
Bachmann N , author
von Braun A , author
Labhardt ND , author
Kadelka C , author
Günthard HF , author
Sekaggya-Wiltshire C , author
Castelnuovo B , author
Kambugu A , author
Lejone TI , author
Böni J , author
Yerly S , author
Perreau M , author
Swiss HIV Cohort Study , author
Date:
2019-02-01
Journal:
The Journal of antimicrobial chemotherapy
Content:
Identifiers:
PMID: 30476115
DOI: 10.1093/jac/dky436
Elevated Aspergillus-specific antibody levels among HIV infected Ugandans with pulmonary tuberculosis.
Authors:
Kwizera R , author
Parkes-Ratanshi R , author
Page ID , author
Sekaggya-Wiltshire C , author
Musaazi J , author
Fehr J , author
Castelnuovo B , author
Kambugu A , author
Denning DW , author
Date:
2017-11-01
Journal:
BMC pulmonary medicine
Content:
Identifiers:
PMID: 29162063
PMC: PMC5699185
DOI: 10.1186/s12890-017-0500-9
The Influence of Pharmacogenetic Variants in HIV/Tuberculosis Coinfected Patients in Uganda in the SOUTH Study.
Authors:
Calcagno A , author
Cusato J , author
Sekaggya-Wiltshire C , author
von Braun A , author
Motta I , author
Turyasingura G , author
Castelnuovo B , author
Fehr J , author
Di Perri G , author
Lamorde M , author
Date:
2019-03-01
Journal:
Clinical pharmacology and therapeutics
Content:
Identifiers:
PMID: 30779340
DOI: 10.1002/cpt.1403
HIV-1 Drug Resistance Among Ugandan Adults Attending an Urban Out-Patient Clinic.
Authors:
von Braun A , author
Sekaggya-Wiltshire C , author
Bachmann N , author
Ssemwanga D , author
Scherrer AU , author
Nanyonjo M , author
Kapaata A , author
Kaleebu P , author
Günthard HF , author
Castelnuovo B , author
Fehr J , author
Kambugu A , author
Date:
2018-08-01
Journal:
Journal of acquired immune deficiency syndromes (1999)
Content:
Identifiers:
PMID: 29771783
DOI: 10.1097/qai.0000000000001717
Pharmacokinetic and pharmacodynamic considerations of rifamycin antibiotics for the treatment of tuberculosis.
Authors:
Sekaggya-Wiltshire C , author
Dooley KE , author
Date:
2019-07-01
Journal:
Expert opinion on drug metabolism & toxicology
Content:
Identifiers:
PMID: 31339806
DOI: 10.1080/17425255.2019.1648432

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