icon-folder.gif   Conference Reports for NATAP  
  ICAAC 2014 54th Interscience Conference
on Antimicrobial Agents and Chemotherapy
September 5-9, 2014, Washington, DC
Back grey_arrow_rt.gif
Switch From RTV to COBI To Boost a PI With Moderate Kidney Impairment
  ICAAC 2014. September 5-9, 2014. Washington, DC
ICAAC: Switching from Ritonavir (RTV) to Cobicistat (COBI) in HIV Patients with Renal Impairment Who Are Virologically Suppressed on a Protease Inhibitor based Regimen - (09/09/14)
Mark Mascolini
Among people with moderate renal impairment (creatinine clearance [CrCl] 50 to 89 mL min), switching from ritonavir to cobicistat as a protease inhibitor (PI) booster yielded 48-week renal impairment results consistent with long-term findings with cobicistat in people without renal impairment [1]. Seven of 73 people stopped the cobicistat regimen for adverse events, 2 of them renal, neither of whom had proximal renal tubulopathy.
In the United States, cobicistat-boosted elvitegravir plus tenofovir/emtricitabine is licensed for first-line antiretroviral therapy in people with CrCl at or above 70 mL/min. European authorities have licensed cobicistat as a stand-alone agent to boost PIs and the FDA is considering that indication. Cobicistat is associated with nonprogressive reductions in CrCl during the first weeks of therapy.
To assess the virologic and safety impact of a cobicistat-boosted PI regimen in people with CrCl of 50 to 89 mL/min, researchers conducted a single-arm study in which adults taking a suppressive ritonavir-boosted atazanavir or darunavir regimen traded ritonavir for cobicistat while retaining the PI and other drugs in the regimen.
The 73 study participants averaged 54 years in age, 60 (82%) were men, and 14 (19%) were black. CD4 count averaged 627 and median viral load stood at 1.69 log10 (about 50 copies). Median serum creatinine measured 1.23 mg/dL (109 (umol/L) and median CrCl 71 mL/min (range 42 to 98). Almost half of study participants, 47%, had CrCl below 70 mL/min, and one third had proteinuria. While 38% had hypertension, 18% had diabetes, and 3% had HIV-associated nephropathy.
Forty-eight weeks after the switch to cobicistat, an FDA snapshot analysis determined the 82% of participants had a viral load below 50 copies. In a missing-data-excluded analysis, 97% had a week-48 viral load below 50 copies. Resistance did not develop to any regimen component in any study participant.
Nineteen of 73 people (26%) stopped the cobicistat regimen, 7 (10%) because of adverse events. The other discontinuations were attributed to investigator discretion, withdrawn consent, loss to follow-up, and protocol violation. Among the 7 people who stopped the regimen because of adverse events, 2 did so because of renal events, neither of them proximal renal tubulopathy. No one in the study had subclinical proximal renal tubulopathy, defined as more than 1 confirmed renal laboratory abnormality, including a serum creatinine increase of 0.4 mg/dL or more, a grade 2 or greater increase in proteinuria, a grade 1 or greater increase in normoglycemic glycosuria, or hypophosphatemia.
Median (and interquartile range [IQR]) changes in CrCl through 48 weeks were:
-- Overall: -3.8 mL/min (IQR -9 to 0.8)
-- If baseline CrCl below 70: -1.1 mL/min (IQR -6.5 to 6.3)
-- If baseline CrCl at or above 70: -6.6 mL/min (IQR -12.4 to -0.7)
Median cystatin C-calculated estimated glomerular filtration rate (eGFR) through 48 weeks was -4.7 mL/min (IQR -11.7 to 3.9). Median actual GFR determined by iohexol clearance measured 82.5 mL/min at baseline, rose 7.0 mL/min at week 4, and fell 4.1 mL/min at week 24. Confirmed renal lab abnormalities after the switch to cobicistat were 3 creatinine gains of at least 0.4 mg/dL, 1 grade 1 case of hypophosphatemia, and 1 grade 2 case of proteinuria. Eight people (11%) had hyperbilirubinemia after the switch, all of them taking atazanavir.
1. McDonald C, Martorell C, Ramgopal M, et al. Efficacy And safety of switching the pharmacoenhancer from ritonavir to cobicistat in HIV patients with renal impairment who are virologically suppressed on a protease inhibitor containing regimen. ICAAC 2014. September 5-9, 2014. Washington, DC. Abstract H-1006.