@article{15f3cd09ed4149819ef2ae099a8b0cf0,
title = "Raltegravir pharmacokinetics before and during treatment with ombitasvir, paritaprevir/ritonavir plus dasabuvir in adults with human immunodeficiency virus-1 and hepatitis C virus coinfection: AIDS Clinical Trials Group sub-study A5334s",
abstract = "Aims: AIDS Clinical Trials Group study A5334s evaluated the pharmacokinetics of raltegravir before and during combined administration of ombitasvir, paritaprevir/ritonavir, plus dasabuvir (OBV/PTV/r + DSV) and weight-based ribavirin in human immunodeficiency virus (HIV) and hepatitis C virus (HCV) coinfected adults. The pharmacokinetics of OBV/PTV/r + DSV during raltegravir coadministration were also characterized. Methods: Adults living with HIV/HCV coinfection receiving steady-state raltegravir (400 mg twice daily) with 2 nucleos(t)ide analogues were enrolled. Pharmacokinetics of raltegravir were assessed prior to HCV therapy, and 4 weeks later following initiation of OBV/PTV/r (25/150/100 mg) once daily + DSV (250 mg) twice daily. Geometric mean ratios (GMRs) and 90% confidence intervals (CIs) were used to compare the following: raltegravir pharmacokinetics with HCV therapy (week 4) vs before HCV therapy (week 0); OBV/PTV/r and DSV pharmacokinetics vs historical healthy controls; raltegravir pharmacokinetics at week 0 vs historical control adults living with HIV. Results: Eight of 11 participants had decreased raltegravir exposures after initiation of HCV therapy. The GMRs (90% CI) for maximum concentration and area under the concentration–time curve of raltegravir with vs without HCV therapy were 0.68 (0.38–1.19) and 0.82 (0.58–1.17), respectively. Comparing OBV/PTV/r pharmacokinetics in healthy controls, A5334s study participants demonstrated generally lower maximum concentration and area under the concentration–time curve values by 41–82% and 4–73%, respectively. Raltegravir exposures tended to be higher in A5334s study participants compared to adults living with HIV. Conclusions: The majority of participants' plasma raltegravir exposures were lower after initiation of HCV therapy in coinfected adults; however, confidence intervals were wide.",
keywords = "HIV/AIDS, antiretrovirals, drug interactions, hepatitis, pharmacokinetics",
author = "Venuto, {Charles S.} and Cramer, {Yoninah S.} and Rosenkranz, {Susan L.} and Mark Sulkowski and Wyles, {David L.} and Cohen, {Daniel E.} and Jeffrey Schmidt and Alston-Smith, {Beverly L.} and Morse, {Gene D.}",
note = "Funding Information: We thank the A5334s study participants, and study site investigators and staff for their time and effort in seeing the completion of this study. We acknowledge the following enrolling Clinical Research Sites (CRS) supported by the National Institute of Allergy and Infectious Diseases (site and funding numbers provided) for A5334s: Puerto Rico AIDS Clinical Trials Unit CRS (site: 5401; grant: UM1AI069415); Cincinnati CRS (site 2401; grant: UM1AI069501); Rush University CRS (site: 2702; grant: UM1AI069471); Alabama CRS (site: 31788; grant: UM1AI069432); University of California, Los Angeles CARE Center CRS (site 601; grant: UM1AI069424); Houston AIDS Research Team CRS (site: 31473; grant: UM1AI069503); University of Washington AIDS Clinical Trials Unit CRS (site 1401; grant: UM1AI069481). We also thank Dr Cindy Bednasz (University at Buffalo, SUNY) for assistance in validating the pharmacokinetic analyses. In addition, we would like to acknowledge contributions, either financial and/or drug related, made by AbbVie. Research reported in this publication was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Number UM1 AI068634, UM1 AI068636 and UM1 AI106701. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Research was also supported in part by the University at Buffalo Pharmacology Specialty Laboratory under award number UM1 AI106701. C.S. Venuto was supported in part by K23AI108355 from the National Institute of Allergy and Infectious Diseases and the University of Rochester CTU (site 1101; grant: UM1AI069511). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Funding Information: We thank the A5334s study participants, and study site investigators and staff for their time and effort in seeing the completion of this study. We acknowledge the following enrolling Clinical Research Sites (CRS) supported by the National Institute of Allergy and Infectious Diseases (site and funding numbers provided) for A5334s: Puerto Rico AIDS Clinical Trials Unit CRS (site: 5401; grant: UM1AI069415); Cincinnati CRS (site 2401; grant: UM1AI069501); Rush University CRS (site: 2702; grant: UM1AI069471); Alabama CRS (site: 31788; grant: UM1AI069432); University of California, Los Angeles CARE Center CRS (site 601; grant: UM1AI069424); Houston AIDS Research Team CRS (site: 31473; grant: UM1AI069503); University of Washington AIDS Clinical Trials Unit CRS (site 1401; grant: UM1AI069481). We also thank Dr Cindy Bednasz (University at Buffalo, SUNY) for assistance in validating the pharmacokinetic analyses. In addition, we would like to acknowledge contributions, either financial and/or drug related, made by AbbVie. Research reported in this publication was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Number UM1 AI068634, UM1 AI068636 and UM1 AI106701. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Research was also supported in part by the University at Buffalo Pharmacology Specialty Laboratory under award number UM1 AI106701. C.S. Venuto was supported in part by K23AI108355 from the National Institute of Allergy and Infectious Diseases and the University of Rochester CTU (site 1101; grant: UM1AI069511). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Publisher Copyright: {\textcopyright} 2019 The British Pharmacological Society",
year = "2020",
month = jan,
day = "1",
doi = "10.1111/bcp.14148",
language = "English (US)",
volume = "86",
pages = "132--142",
journal = "British Journal of Clinical Pharmacology",
issn = "0306-5251",
publisher = "Wiley-Blackwell",
number = "1",
}