144w Renal Safety of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF from Two Phase 3 RCTs

Jan Gerstoft1, Calvin Cohen2, Frank Post3, Bruce Hendry3, Pierre-Marie Girard4, Gerd Faetkenheuer5, Andrea Antinori6, Martin Fisher7, Martin S Rhee8, Javier Szwarcberg8
Affiliates: 1Rigshospitalet, Klinik for Infektion, Copenhagen, Denmark, 2Community Research Initiative, Boston, 3King’s College London School of Medicine, London, 4Hôpital Saint-Antoine, Université Pierre et Marie Curie, Paris, France, 5University Hospital of Cologne, Cologne, Germany, 6Istituto Nazionale per le Malattie Infettive, Rome Italy, 7Brighton and Sussex Medical School, Brighton, United Kingdom, 8Gilead Sciences Inc., Foster City, CA, USA.

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Background
Elvitegravir/cobicistat/emtricitabine (FTC)/tenofovir DF (STB) is approved for the treatment of HIV-1 infection in patients with estimated creatinine clearance (eCrCL) ≥ 70 mL/min. Similar to ritonavir, cobicistat inhibits renal creatinine secretion, leading to a small increase in serum creatinine, without affecting the actual GFR

Methods
Pooled 144-week data from two randomized, double-blinded, active-controlled clinical trials were analyzed for renal safety by baseline eCrCL (mL/min): Study 103 (STB vs ritonavir-boosted atazanavir [ATV+RTV] + FTC/TDF [TVD]) and Study 102 (STB vs efavirenz/FTC/TDF [ATR]). The entry criterion for eCrCL was ≥ 70.

Results
Rates of renal discontinuations were STB 1.9% (13/701) vs ATV+RTV+TVD 2.3% (8/355) vs ATR 0/352. Of those, 0.6% (4/701) vs 0.8% (3/355) vs 0% (0/352) developed proximal renal tubulopathy (PRT). The 4 STB PRT cases occurred before Week 24; 3 ATV+RTV+TVD PRT cases occurred before Week 48. All PRT cases improved after study drug discontinuation. Median (IQR) changes in eCrCL at Week 144 were STB -13.9 [-24.0 to -3.1], ATV+RTV+TVD -10.0 [-19.3 to -0.2], ATR -2.0 [-10.9 to 8.1], and similar to those at Week 48 and 96. In both subgroups of baseline eCrCL (70 to <90 and ≥90), the declines in eCrCL in STB and ATV+RTV+TVD were greater than ATR. Tubular abnormalities were similar between treatment groups regardless of baseline eCrCL. For STB patients with baseline eCrCL 70 to <90, the decline in eCrCL was smaller relative to those with higher baseline eCrCL.

Conclusions
No STB patient developed PRT after Week 24. The rate of renal discontinuations in STB group was low and similar to those in ATV+RTV+TVD group, and consistent with historical rates. The renal safety of STB in patients with baseline eCrCL 70 to <90 was similar to those with higher baseline eCrCL, and to the two comparator regimens.