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Switching from ritonavir to cobicistat in HIV patients with renal impairment who are virologically suppressed on a protease inhibitor

INTRODUCTION: Cobicistat (COBI) is a pharmacoenhancer and one of the components of ECF/TDF (elvitegravir/cobicistat/emtricitabine/tenofovir DF), which is approved in treatment-naïve HIV patients with creatinine clearance (CrCl) ≥70 mL/min. Study 118 assessed the renal safety of COBI-containing regim...

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Autores principales: Fisher, Martin, McDonald, Cheryl, Moyle, Graeme, Martorell, Claudia, Ramgopal, Moti, Laplante, Francois, Curley, Joanne, Graham, Hiba, Tran-Muchowski, Cecilia, Liu, Yapei, Rhee, Martin, Szwarcberg, Javier
Formato: Online Artículo Texto
Lenguaje:English
Publicado: International AIDS Society 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4225380/
https://www.ncbi.nlm.nih.gov/pubmed/25397568
http://dx.doi.org/10.7448/IAS.17.4.19824
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author Fisher, Martin
McDonald, Cheryl
Moyle, Graeme
Martorell, Claudia
Ramgopal, Moti
Laplante, Francois
Curley, Joanne
Graham, Hiba
Tran-Muchowski, Cecilia
Liu, Yapei
Rhee, Martin
Szwarcberg, Javier
author_facet Fisher, Martin
McDonald, Cheryl
Moyle, Graeme
Martorell, Claudia
Ramgopal, Moti
Laplante, Francois
Curley, Joanne
Graham, Hiba
Tran-Muchowski, Cecilia
Liu, Yapei
Rhee, Martin
Szwarcberg, Javier
author_sort Fisher, Martin
collection PubMed
description INTRODUCTION: Cobicistat (COBI) is a pharmacoenhancer and one of the components of ECF/TDF (elvitegravir/cobicistat/emtricitabine/tenofovir DF), which is approved in treatment-naïve HIV patients with creatinine clearance (CrCl) ≥70 mL/min. Study 118 assessed the renal safety of COBI-containing regimens in HIV patients with mild to moderate renal impairment. MATERIAL AND METHODS: Phase 3, open label study in HIV-1-infected patients with CrCl 50–89 mL/min who are virologically suppressed on a stable regimen containing ritonavir (RTV)-boosted atazanavir (ATV) or darunavir (DRV). Patients switched RTV to COBI, while keeping the rest of their regimen unchanged. We present the 96-week (Wk) data. RESULTS: Seventy-three patients were enrolled. Mean age was 54 years; male 82%; white 77%; hypertension 38%; diabetes 18%; baseline proteinuria (≥trace) 51%; median CrCl 71 mL/min (range: 42–98). At Wk 96, 89% maintained virologic suppression (95% CI 77.4–95.8%). No emergent resistance developed. Reductions in CrCl (median [IQR]) were observed as early as Wk 2, after which they were nonprogressive through Wk 96 (Wk 48: −3.8 [−9–0.8]; Wk 96: −5.0 [−13.0–0.1]). Changes in CrCl by baseline CrCl (<70 vs ≥70) at Wk 96 were: −3.1 [−5.1–0.5] vs −7.6 [−15.2 to −3.6], respectively. Cystatin C-based eGFR remained stable through Wk 96 (median [IQR]: −2.8 [−7.4–8.9 mL/min/1.73 m(2)). Actual GFR assessment using CL(iohexol) (n=14) was unaffected over 24 Wks (median at baseline: 82.5, median changes from baseline at Wks 2, 4, and 24: 1.6, 7.0, −4.1 mL/min, respectively). Three renal discontinuations occurred (two worsening CrCl and one proteinuria/hematuria); none had proximal renal tubulopathy [PRT]. No patient had laboratory evidence of PRT (>1 confirmed renal laboratory abnormalities [increase in serum Cr≥0.4 mg/dL, ≥2-grade increase in proteinuria,≥1-grade increase in normoglycemic glycosuria or hypophosphatemia]). CONCLUSIONS: In HIV-infected patients with CrCl 50–89 mL/min, on ATV- or DRV-based regimen switching to COBI from RTV, demonstrated that COBI was well tolerated with no cases of PRT through 96 Wks. The renal safety profile of COBI in patients with mild to moderate renal impairment was consistent with the long-term data in patients without renal impairment (CrCl≥70 mL/min) from the phase 3 studies of COBI-containing regimens.
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spelling pubmed-42253802014-11-13 Switching from ritonavir to cobicistat in HIV patients with renal impairment who are virologically suppressed on a protease inhibitor Fisher, Martin McDonald, Cheryl Moyle, Graeme Martorell, Claudia Ramgopal, Moti Laplante, Francois Curley, Joanne Graham, Hiba Tran-Muchowski, Cecilia Liu, Yapei Rhee, Martin Szwarcberg, Javier J Int AIDS Soc Poster Sessions – Abstract P292 INTRODUCTION: Cobicistat (COBI) is a pharmacoenhancer and one of the components of ECF/TDF (elvitegravir/cobicistat/emtricitabine/tenofovir DF), which is approved in treatment-naïve HIV patients with creatinine clearance (CrCl) ≥70 mL/min. Study 118 assessed the renal safety of COBI-containing regimens in HIV patients with mild to moderate renal impairment. MATERIAL AND METHODS: Phase 3, open label study in HIV-1-infected patients with CrCl 50–89 mL/min who are virologically suppressed on a stable regimen containing ritonavir (RTV)-boosted atazanavir (ATV) or darunavir (DRV). Patients switched RTV to COBI, while keeping the rest of their regimen unchanged. We present the 96-week (Wk) data. RESULTS: Seventy-three patients were enrolled. Mean age was 54 years; male 82%; white 77%; hypertension 38%; diabetes 18%; baseline proteinuria (≥trace) 51%; median CrCl 71 mL/min (range: 42–98). At Wk 96, 89% maintained virologic suppression (95% CI 77.4–95.8%). No emergent resistance developed. Reductions in CrCl (median [IQR]) were observed as early as Wk 2, after which they were nonprogressive through Wk 96 (Wk 48: −3.8 [−9–0.8]; Wk 96: −5.0 [−13.0–0.1]). Changes in CrCl by baseline CrCl (<70 vs ≥70) at Wk 96 were: −3.1 [−5.1–0.5] vs −7.6 [−15.2 to −3.6], respectively. Cystatin C-based eGFR remained stable through Wk 96 (median [IQR]: −2.8 [−7.4–8.9 mL/min/1.73 m(2)). Actual GFR assessment using CL(iohexol) (n=14) was unaffected over 24 Wks (median at baseline: 82.5, median changes from baseline at Wks 2, 4, and 24: 1.6, 7.0, −4.1 mL/min, respectively). Three renal discontinuations occurred (two worsening CrCl and one proteinuria/hematuria); none had proximal renal tubulopathy [PRT]. No patient had laboratory evidence of PRT (>1 confirmed renal laboratory abnormalities [increase in serum Cr≥0.4 mg/dL, ≥2-grade increase in proteinuria,≥1-grade increase in normoglycemic glycosuria or hypophosphatemia]). CONCLUSIONS: In HIV-infected patients with CrCl 50–89 mL/min, on ATV- or DRV-based regimen switching to COBI from RTV, demonstrated that COBI was well tolerated with no cases of PRT through 96 Wks. The renal safety profile of COBI in patients with mild to moderate renal impairment was consistent with the long-term data in patients without renal impairment (CrCl≥70 mL/min) from the phase 3 studies of COBI-containing regimens. International AIDS Society 2014-11-02 /pmc/articles/PMC4225380/ /pubmed/25397568 http://dx.doi.org/10.7448/IAS.17.4.19824 Text en © 2014 Fisher M et al; licensee International AIDS Society http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Poster Sessions – Abstract P292
Fisher, Martin
McDonald, Cheryl
Moyle, Graeme
Martorell, Claudia
Ramgopal, Moti
Laplante, Francois
Curley, Joanne
Graham, Hiba
Tran-Muchowski, Cecilia
Liu, Yapei
Rhee, Martin
Szwarcberg, Javier
Switching from ritonavir to cobicistat in HIV patients with renal impairment who are virologically suppressed on a protease inhibitor
title Switching from ritonavir to cobicistat in HIV patients with renal impairment who are virologically suppressed on a protease inhibitor
title_full Switching from ritonavir to cobicistat in HIV patients with renal impairment who are virologically suppressed on a protease inhibitor
title_fullStr Switching from ritonavir to cobicistat in HIV patients with renal impairment who are virologically suppressed on a protease inhibitor
title_full_unstemmed Switching from ritonavir to cobicistat in HIV patients with renal impairment who are virologically suppressed on a protease inhibitor
title_short Switching from ritonavir to cobicistat in HIV patients with renal impairment who are virologically suppressed on a protease inhibitor
title_sort switching from ritonavir to cobicistat in hiv patients with renal impairment who are virologically suppressed on a protease inhibitor
topic Poster Sessions – Abstract P292
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4225380/
https://www.ncbi.nlm.nih.gov/pubmed/25397568
http://dx.doi.org/10.7448/IAS.17.4.19824
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