• HIV & AIDS
• Infectious Disease Clinical Trials

• HIV & AIDS
• Infectious Disease
• Infectious Disease Clinical Trials

Claudia Martorell, MD, MPH, The Commonwealth Research Institute, Springfield, Massachusetts, USA, and colleagues have reported that cobicistat (COBI; approved as Tybost™ in the European Union and under review in the United States) is well tolerated in HIV-1 patients with mild-to-moderate renal impairment.

The latest results build on prior phase 3 data demonstrating the long-term (144-week) noninferiority of COBI—which is eliminated mainly by liver metabolism, negating the need for dose adjustment in renal-impaired patients—to ritonavir (RTV) as a protease inhibitor (PI) booster in treatment of HIV-1 infection in treatment-naïve patients. In this study and studies of EVG/COBI/FTC/TDF (STB), the evaluations were done in patients with a creatinine clearance (CrCl) ≥ 70 mL/min. The latest data obtained with patients with CrCl as low as 50 mL/min solidify the view that switching from ritonavir to cobicistat in this patient population is feasible.

This study involved 73 intent-to-treat HIV-1-infected patients who were virologically suppressed (< 50 copies/mL HIV-1 RNA for at least 6 months) with mild-to-moderate renal impairment as indicated by a CrCl of 50 to 89 mL/min (Table 1).

The study assessed adverse events, estimated glomerular filtration rate (eGFR) according to creatinine-based CrCl and cystatin C-based eGFR, actual GFR according to iohexol plasma clearance, and laboratory analyses of urine protein, urine glucose, and serum phosphorus.

Patients were receiving a regimen of RTV plus either atazanavir (ATV) or darunavir (DRV) plus 2 nucleoside-nucleotide reverse transcriptase inhibitors prior to baseline. COBI was substituted for RTV, whereas other agents were continued. The present results were from week 48 of the planned 96-week therapeutic course.

Median CrCl declined marginally early after the switch to COBI and remained stable through week 48 (overall, −3.8; interquartile range [IQR], −9.0 to 0.8). Patients with baseline low CrCl (< 70 mL/min) displayed nearly no change in CrCl throughout 48 weeks (−1.1; IQR, −6.5 to 6.3), whereas patients with baseline CrCl ≥ 70 mL/min displayed a greater decline from baseline, which remained stable for most of the treatment (−6.6; IQR, −12.4 to −0.7). No clinically relevant changes in cystatin-based eGFR were evident through week 48 (−4.7; IQR, −11.7 to 3.9). Actual GFR was not appreciably affected through week 24 (Table 2).

Three patients had increased serum creatinine ≥ 0.4 mg/dL, but none of them had confirmed proteinuria or hypophosphatemia. Proteinuria was present at baseline in 43% and 21% of patients with CrCl < 70 and ≥ 70 mL/min, respectively. At week 48, the rate of confirmed proteinuria was 14% and 11%, in the same respective order. Adverse events included upper respiratory tract infection (19%), nasopharyngitis (12%), nausea (12%), diarrhea (11%), headache (11%), and hyperbilirubinemia (11%). The latter occurred exclusively in those receiving ATV. Events prompting discontinuation were headache (n = 2) and nausea (n = 2). COBI was not associated with discontinuation due to proximal renal tubulopathy.

In summary, the switch from RTV to COBI as a pharmacoenhancer plus 2 NRTIs was associated with a high rate of continued virologic suppression in HIV-1 patients with mild-to-moderate renal impairment. No viral resistance was evident. The adverse events were consistent with the known safety profile of COBI. The findings further support the potential of COBI as an alternative pharmacoenhancer of PI in virologically suppressed, HIV-1-infected patients with mild-to-moderate renal impairment.

• © 2014 MD Conference Express®