The safety, effectiveness and concentrations of adjusted lopinavir/ritonavir in HIV-infected adults on rifampicin-based antitubercular therapy

Eric H Decloedt, Gary Maartens, Peter Smith, Concepta Merry, Funeka Bango, Helen McIlleron, Eric H Decloedt, Gary Maartens, Peter Smith, Concepta Merry, Funeka Bango, Helen McIlleron

Abstract

Objective: Rifampicin co-administration dramatically reduces plasma lopinavir concentrations. Studies in healthy volunteers and HIV-infected patients showed that doubling the dose of lopinavir/ritonavir (LPV/r) or adding additional ritonavir offsets this interaction. However, high rates of hepatotoxicity were observed in healthy volunteers. We evaluated the safety, effectiveness and pre-dose concentrations of adjusted doses of LPV/r in HIV infected adults treated with rifampicin-based tuberculosis treatment.

Methods: Adult patients on a LPV/r-based antiretroviral regimen and rifampicin-based tuberculosis therapy were enrolled. Doubled doses of LPV/r or an additional 300 mg of ritonavir were used to overcome the inducing effect of rifampicin. Steady-state lopinavir pre-dose concentrations were evaluated every second month.

Results: 18 patients were enrolled with a total of 79 patient months of observation. 11/18 patients were followed up until tuberculosis treatment completion. During tuberculosis treatment, the median (IQR) pre-dose lopinavir concentration was 6.8 (1.1-9.2) mg/L and 36/47 (77%) were above the recommended trough concentration of 1 mg/L. Treatment was generally well tolerated with no grade 3 or 4 toxicity: 8 patients developed grade 1 or 2 transaminase elevation, 1 patient defaulted additional ritonavir due to nausea and 1 patient developed diarrhea requiring dose reduction. Viral loads after tuberculosis treatment were available for 11 patients and 10 were undetectable.

Conclusion: Once established on treatment, adjusted doses of LPV/r co-administered with rifampicin-based tuberculosis treatment were tolerated and LPV pre-dose concentrations were adequate.

Conflict of interest statement

Competing Interests: The authors have declared that no competing conflicts exist.

Figures

Figure 1. The profile of the study…
Figure 1. The profile of the study cohort.
Figure 2. Lopinavir concentrations of individual patients…
Figure 2. Lopinavir concentrations of individual patients during the study period.
The circles indicate lopinavir concentrations measured while patients were receiving tuberculosis treatment, while the squares indicate lopinavir concentrations once tuberculosis treatment has been completed.

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