Aims: Patients hospitalized at the time of human immunodeficiency virus-associated
tuberculosis (HIV-TB) diagnosis have high early mortality. We hypothesized that
compared to outpatients, there would be lower antituberculosis drug exposure in
hospitalized HIV-TB patients, and amongst hospitalized patients exposure would be
lower in patients who die or have high lactate (a sepsis marker).
Methods: We performed pharmacokinetic sampling in hospitalized HIV-TB patients
and outpatients. Plasma rifampicin, isoniazid and pyrazinamide concentrations were
measured in samples collected predose and at 1, 2.5, 4, 6 and 8 hours on the third
day of standard antituberculosis therapy. Twelve-week mortality was ascertained for
inpatients. Noncompartmental pharmacokinetic analysis was performed.
Results: Pharmacokinetic data was collected in 59 hospitalized HIV-TB patients and
48 outpatients. Inpatient twelve-week mortality was 11/59 (19%). Rifampicin,
isoniazid and pyrazinamide exposure was similar between hospitalized and
outpatients (Cmax:7.4 vs. 8.3 μg·mL-1, p=0.223; 3.6 vs. 3.5 μg·mL-1, p=0.569; 50.1 vs.
46.8 μg·mL-1, p=0.081; AUC0-8:41.0 vs. 43.8 mg·h·L-1, p= 0.290; 13.5 vs. 12.4
mg·h·L-1, p=0.630; 316.5 vs. 292.2 mg·h·L-1, p=0.164, respectively) and not lower in
inpatients who died. Rifampicin and isoniazid Cmax were below recommended ranges
in 61% and 39% inpatients and 44% and 35% outpatients. Rifampicin exposure was
higher in patients with lactate >2.2mmol·L-1.
Conclusion: Mortality in hospitalized HIV-TB patients was high. Early antituberculosis
drug exposure was similar to outpatients and not lower in inpatients who died.
Rifampicin and isoniazid Cmax were sub-optimal in 61% and 39% of inpatients and
rifampicin exposure was higher in patients with high lactate. Treatment strategies
need to be optimized to improve survival.