A quest to optimize the clinical pharmacology of tuberculosis and human immunodeficiency virus drug treatment

TB currently is the number one killer among infectious diseases, with a sad record of 1.7 million deaths in 2016 alone. HIV infection is the most important risk factor for TB. Patients with TB/HIV co-infection suffer from drug-drug interactions, they have a high pill burden and they have to adjust their lifestyles radically to cure or inhibit their infection. In addition they also have an increased risk for an unsuccessful treatment due to a possibly altered absorption, metabolism or excretion of drugs (due to naturally occurring variation in pharmacokinetics). This thesis focuses on the optimization of the pharmaceutical treatment of TB in people with both an HIV and TB infection and also on the optimal use of the antiretroviral drug darunavir.
We provided insight on the effect of HIV-infection on the exposure to first-line TB drugs by assessing published literature. Due to the complexity of the TB bacteria people with TB have to be treated 6 months with TB drugs. In daily practice however, a proportion of the patients is treated longer than 6 months. We therefore also studied the potential risk factors contributing to a prolonged TB treatment. Further, we provided insight in the complexity of the treatment of people with TB/HIV co-infection by describing the treatment of individual patient.
In addition, we have also developed methods, such as a laboratory test and an algorithm, which could contribute to customized darunavir therapy. We also investigated the food intake of people using darunavir in order to promote healthy food intake.