TB drug interactions among people living with HIV in Uganda
20th Anniversary of Global Health Fellows and Scholars
As winner of the 2018 Stephen Lawn TB-HIV Research Leadership Prize award, an award that acknowledges young researchers conducting promising work focused on reducing the disease burden of tuberculosis (TB) and HIV/AIDS in Africa, Dr. Christine Sekaggya-Wiltshire, is considered a trailblazer in her field of study.
A clinical scientist who leads the TB and HIV clinic at the Infectious Diseases Institute (IDI) at Makerere University, Dr. Sekaggya-Wiltshire also works as a physician in the hematology unit at Mulago Hospital. Her research at IDI focuses on drug pharmacokinetics, the study of how drugs are absorbed and metabolized to better understand their impact on the patient. As an investigator in pharmacokinetic studies, she specifically focuses on the interaction between anti-tuberculosis drugs and antiretroviral drugs taken by people living with HIV. TB drugs are known for their high levels of toxicity that can often cause adverse events like nerve pain and bone marrow suppression, especially in patients co-infected with HIV.
The first phase of her Fogarty project, which was the foundation of her Ph.D., was a systematic review of the existing literature on the correlation between the blood concentration of anti-TB drugs and treatment outcomes in TB-HIV co-infected patients. At the time, Sekaggya-Wiltshire found conflicting evidence around whether or not concentrations of anti-TB drugs in the blood correlate with the level of toxicity to the patient and, ultimately, whether or not these concentrations are associated with curing TB disease. In her larger Ph.D. project, Sekaggya-Wiltshire studied a cohort of 268 patients to determine if the blood concentration of anti-TB drugs was associated with toxicity and time to cure among patients living with HIV.
She found through this review, and the cohort study, that people living with HIV who were treated with the recommended doses of Rifampin and Isoniazid, two common anti-TB drugs, were not achieving the recommended concentration of the drugs in their systems, and there was no correlation between the level of anti-TB drugs and toxicity to the patient. While toxicity levels were not affected, more studies are needed to determine if these lower levels of anti-TB drugs in patients' blood are enough to fight off TB microorganisms.
Since completing her Fogarty Fellowship, Sekaggya-Wiltshire serves as a mentor for up-and-coming Fogarty Fellows at IDI. "Seeing what it takes to complete this project independently from inception to publication and helping others do the same has been invaluable to my career."
Today, Sekaggya-Wiltshire continues to supervise care for complex cases of TB and is currently studying the clinical predictors of adverse reactions related to TB preventive therapy in people with and without HIV, with support from the National Institute of Allergy and Infectious Diseases (NIAID). Her current study aims to describe the adverse events or drug reactions people get when taking a three-month regimen of TB preventive medication and to determine who is susceptible to these adverse events and what determines who will experience them.
She hopes to continue building capacity for pharmacokinetics research in sub-Saharan Africa, especially for early-phase clinical trials, which are often started in the west and later brought to the region. Though this type of search is not as common in Uganda as it is in the West, Wiltshire and her team at IDI have begun training doctors, nurses, and pharmacists to conduct such studies and to expand their capacity further.
"We need to build our capacity to implement early-phase clinical trials here not only for the researchers but patients as well because the burden of disease is here."
Reflecting on the number of applications she has had to submit up to this point in her career, she advises her mentees and future researchers at Makerere University "to never overlook an opportunity no matter how big or small it might be and never give up."
Updated August 14, 2023
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