Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012;7(3):e32173.
doi: 10.1371/journal.pone.0032173. Epub 2012 Mar 7.

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

Eric H Decloedt  1 , Gary Maartens, Peter Smith, Concepta Merry, Funeka Bango, Helen McIlleron
Affiliations

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

Eric H Decloedt et al. PLoS One. 2012.

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.

PubMed Disclaimer

Conflict of interest statement

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

Figures

Figure 1
Figure 1. The profile of the study cohort.
Figure 2
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.
See this image and copyright information in PMC

References

    1. Lawn SD, Myer L, Edwards D, Bekker LG, Wood R. Short-term and long-term risk of tuberculosis associated with CD4 cell recovery during antiretroviral therapy in South Africa. AIDS. 2009;Aug 24;23(13):1717–1725. - PMC - PubMed
    1. CDC. Managing Drug Interactions in the Treatment of HIV-Related Tuberculosis. 2007. Available: http://www.cdc.gov/tb/publications/guidelines/HIV_AIDS.htm. Accessed 2010 Aug 13.
    1. la Porte CJ, Colbers EP, Bertz R, Voncken DS, Wikstrom K, et al. Pharmacokinetics of adjusted-dose lopinavir-ritonavir combined with rifampin in healthy volunteers. Antimicrob Agents Chemother. 2004;May;48(5):1553–1560. - PMC - PubMed
    1. Decloedt EH, McIlleron H, Smith P, Merry C, Orrell C, et al. Pharmacokinetics of Lopinavir in HIV-Infected Adults Receiving Rifampin with Adjusted Doses of Lopinavir-Ritonavir Tablets. Antimicrob Agents Chemother. 2011;Jul;55(7):3195–3200. - PMC - PubMed
    1. Unexpected hepatotoxicity observed in a healthy volunteer study on the effects of multiple dose rifampicin on the steady-state pharmacokinetics of ritonavir-boosted sequinavir and vice versa. 2005. Sixth International Workshop on Clinical Pharmacology of HIV therapy; 28–30 April; Montreal, Quebec, Canada.

Publication types

MeSH terms