Open AccessSwitching from ritonavir to cobicistat in HIV patients with renal impairment who are virologically suppressed on a protease inhibitor
Author(s) -
Fisher Martin,
McDonald Cheryl,
Moyle Graeme,
Martorell Claudia,
Ramgopal Moti,
Laplante Francois,
Curley Joanne,
Graham Hiba,
TranMuchowski Cecilia,
Liu Yapei,
Rhee Martin,
Szwarcberg Javier
Publication year - 2014
Publication title -
journal of the international aids society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.724
H-Index - 62
ISSN - 1758-2652
DOI - 10.7448/ias.17.4.19824
Subject(s) - cobicistat , medicine , atazanavir , renal function , elvitegravir , ritonavir , regimen , creatinine , urology , tenofovir alafenamide , darunavir , emtricitabine , gastroenterology , viral load , human immunodeficiency virus (hiv) , immunology , antiretroviral therapy
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.