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Cerebrospinal fluid drug concentrations and viral suppression in HIV-1-infected patients receiving ritonavir-boosted atazanavir plus lamivudine dual antiretroviral therapy (Spanish HIV/AIDS Research Network, PreEC/RIS 39)

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Abstract

This study aimed to assess cerebrospinal fluid (CSF) drug concentrations and viral suppression in HIV-1-infected patients on ritonavir-boosted atazanavir (ATV/r) plus lamivudine (3TC) dual therapy. HIV-1-infected adults with suppressed plasma HIV-1 RNA who switched to ATV/r plus 3TC were studied. Total ATV and 3TC concentrations at the end of the dosing interval (C24h), using a validated LC-MS/MS method, and HIV-1 RNA were measured in paired CSF and plasma samples 12 weeks after switching. Ten individuals were included. Median (range) age was 42.5 (33–70) years, time on ART was 39.5 (11–197) months, and time with plasma HIV-1 RNA < 40 copies/mL was 15.5 (6–46) months. At baseline, CSF HIV-1 RNA was < 40 copies/mL in all patients. Twelve weeks after switching to ATV/r plus 3TC, HIV-1 RNA remained at < 40 copies/mL in both plasma and CSF in 9/10 patients. One patient with suboptimal adherence to ART had HIV-1 RNA rebound in both plasma and CSF. The median CSF-to-plasma concentration ratios of ATV and 3TC were 0.013 and 0.417, respectively. Median ATV C24h in CSF was 10.4 (3.7–33.4) ng/mL (in vitro ATV IC50 range, 1–11 ng/mL). Median 3TC C24h in CSF was 43.4 (16.2–99.3) ng/mL (in vitro 3TC IC50 range, 0.68–20.6 ng/mL). Most patients maintained HIV-1 RNA in CSF < 40 copies/mL despite CSF ATV C24h close to or within the IC50 range in the majority. ATV PK data in CSF should be considered and rigorous patient selection is advisable to assure effective CSF viral suppression with this two-drug simplification regimen.

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Acknowledgements

The authors are grateful to all the patients who participated in this study. We thank Celine Cavallo for English language support. We acknowledge infrastructural support from the Liverpool Biomedical Research Centre funded by the Liverpool Health Partners.

Funding

The study was supported, in part, by the RD16/0025/0003-ISCIII-FEDER.

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Authors and Affiliations

  1. HIV and STI Unit, Department of Infectious Diseases, Bellvitge University Hospital-IDIBELL, Feixa Llarga S/N, L’Hospitalet de Llobregat, 08907, Barcelona, Spain

    Arkaitz Imaz, Elena Ferrer, Juan M Tiraboschi, Laura Acerete, Benito Garcia, Antonia Vila & Daniel Podzamczer

  2. Department of Microbiology, Bellvitge University Hospital-IDIBELL, L’Hospitalet de Llobregat, Barcelona, Spain

    Jordi Niubó

  3. Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK

    Alieu Amara & Saye Khoo

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  1. Arkaitz Imaz
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  2. Jordi Niubó
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Contributions

A.I. and D.P. designed the study; A.I., E.F. and D.P. recruited the participants; A.I., B.G. and A.V. conducted the study visits; J.N. performed the microbiological procedures. A.A. and S.K. performed LCMS/MS to measure ATV and 3TC concentrations in blood plasma and CSF; L.A. assisted in the data collection and study coordination; A.I., J.M.T. and D.P. analysed and interpreted the results; A.I. drafted the manuscript and J.M.T., E.F., S.K. and D.P. reviewed it. All authors revised the manuscript for important intellectual content and contributed to the final version.

This study was presented in part as a poster in the 9th IAS Conference on HIV Science (IAS 2017), 23-36 July 2017, Paris, France.

Corresponding authors

Correspondence to Arkaitz Imaz or Daniel Podzamczer.

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Conflicts of interest

A.I. has received financial compensation for lectures, consultancies, and educational activities, or research funding for from AbbVie, Gilead Sciences, Janssen-Cilag, Merck Sharp & Dohme and ViiV Healthcare. J.N. has received financial compensation for lectures and research from Abbott Molecular. S.K. has received funding from Merck Gilead Sciences Jannsen and ViiV Healthcare for research and support of the HIV drug interactions website. J.M.T. has received financial compensation for lectures, consultancies, and educational activities, or research funding for from AbbVie, Gilead Sciences, Janssen-Cilag, Merck Sharp & Dohme and ViiV Healthcare. E.F. has received honoraria for advisories and/or conferences from Viiv, BMS, Abbott, Gilead, Janssen and Merck. D.P. has received research grants and/or honoraria for advisories and/or conferences from Viiv, BMS, Abbott, Gilead, Janssen and Merck. A.A, L.A., B.G. and A.V. declare no conflicts of interest regarding this article.

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Imaz, A., Niubó, J., Amara, A. et al. Cerebrospinal fluid drug concentrations and viral suppression in HIV-1-infected patients receiving ritonavir-boosted atazanavir plus lamivudine dual antiretroviral therapy (Spanish HIV/AIDS Research Network, PreEC/RIS 39). J. Neurovirol. 24, 391–397 (2018). https://doi.org/10.1007/s13365-018-0626-4

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