Khayelitsha Hospital TB study pharmacokinetic variables: Non compartmental analysis

Human immunodeficiency virus associated tuberculosis (HIV-TB) comprise 10% of global tuberculosis cases but contribute a disproportionate 22% of global tuberculosis mortality. HIV-infected patients hospitalized with HIV-TB have high high case fatality rates despite treatment and often present with a clinical picture compatible with sepsis. There is paucity of data in critically ill HIV-infected patients admitted to hospital at the time of tuberculosis diagnosis. Improved, evidence-based treatment interventions in this patient group are urgently needed to improve survival.We performed intensive pharmacokinetic studies (from 0-8 hours) in a high burden setting (Khayelitsha Hospital, Cape Town), within the routine service. We assessed rifampicin, isoniazid and pyrazinamide exposure in a group of hospitalized HIV-TB patients and a group of outpatients on the third day of standard antituberculosis therapy using non-compartmental analysis. We followed hospitalized patients for 12 weeks to asses survival. We compared pharmacokinetic exposures in hospitalized patients and outpatients; hospitalized patients who survived twelve weeks and those who died; and hospitalized patients presenting with high lactate (more than 2.2 mmol/L) and patient presenting with normal lactate.