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

Christopher Vinnard, Isabel Manley, Brittney Scott, Mariana Bernui, Joella Adams, Sheryl Varghese, Isaac Zentner, Michele A Kutzler, Christopher Vinnard, Isabel Manley, Brittney Scott, Mariana Bernui, Joella Adams, Sheryl Varghese, Isaac Zentner, Michele A Kutzler

Abstract

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.

Figures

Figure 1
Figure 1
Flow cytometry results for CD4+ T cells. Panel 1: gating of lymphocytes; panel 2: live/dead staining; panel 3: CD3+ CD4+; panel 4: CD4+ HLA-DR+; panel 5: CD4+ CD38+; panel 6: CD4+ CD57+.
Figure 2
Figure 2
Flow cytometry results for CD8+ T cells. Panel 1: gating of lymphocytes; panel 2: live/dead staining; panel 3: CD3+ CD8+; panel 4: CD8+ HLA-DR+; panel 5: CD8+ CD38+; panel 6: CD8+ CD57+.
Figure 3
Figure 3
Individual plots of serum rifampin concentration-versus-time curves.

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