A Pilot Study of Immune Activation and Rifampin Absorption in HIV-Infected Patients without Tuberculosis Infection: A Short Report

Background. Rifampin malabsorption is frequently observed in tuberculosis patients coinfected with human immunodeficiency virus (HIV) but cannot be predicted by patient factors such as CD4+ T cell count or HIV viral load. Methods. We sought to describe the relationship between HIV-associated immune activation, measures of gut absorptive capacity and permeability, and rifampin pharmacokinetic parameters in a pilot study of 6 HIV-infected, tuberculosis-uninfected patients who were naïve to antiretroviral therapy. Results. The median rifampin area under the concentration-versus-time curve during the 8-hour observation period was 42.8 mg·hr/L (range: 21.2 to 57.6), with a median peak concentration of 10.1 mg/L (range: 5.3 to 12.5). We observed delayed rifampin absorption, with a time to maximum concentration greater than 2 hours, in 2 of 6 participants. There was a trend towards increased plasma concentrations of sCD14, a marker of monocyte activation in response to bacterial translocation, among participants with delayed rifampin absorption compared to participants with rapid absorption (p=0.06). Conclusions. Delayed rifampin absorption may be associated with elevated markers of bacterial translocation among HIV-infected individuals naïve to antiretroviral therapy. This trial is registered with NCT01845298.