Table 2.
Level 1 randomized controlled trials evaluating renal outcomes in treatment-naïve HIV-1 infected adults commencing PI-containing regimens
| Study ID, references | Design | Regimen comparison | Renal outcome | Comment | Limitations |
|---|---|---|---|---|---|
| GS-US-216-0114, Gallant et al. [33] | 48-week, double-blind, placebo-controlled, double-dummy, multicenter |
ATV/COBI + FTC/TDF (n = 334) vs. ATV/r + FTC/TDF (n = 348) |
Median changes from baseline at 48 weeks: Serum creatinine +11.5 μmol/L ATV/COBI group +8.0 μmol/L ATV/r group (P < 0.001 vs. ATV/COBI, Wilcoxon rank-sum test) eCC using CG equation −12.9 mL/min ATV/COBI group −9.1 mL/min ATV/r group (P < 0.001 vs. ATV/COBI, Wilcoxon rank-sum test) |
Increases in serum creatinine and decreases in eCC in both groups stabilized by 8 weeks and did not change thereafter up to 48 weeks. Changes in the COBI arm significantly greater than in the ATV/r arm |
No baseline serum creatinine or eCC values Patents with eCC <70 mL/min excluded Short follow-up |
| GS-236-0103, DeJesus et al. [34] | 48-week, double-blind, placebo-controlled, quadruple-dummy, multicenter |
EVG/COBI/FTC/TDF ‘QUAD’ (n = 353) vs. ATV/r + FTC/TDF (n = 355) |
Median changes from baseline at 48 weeks: Serum creatinine +11.0 μmol/L QUAD group +7.0 μmol/L ATV/r group (P < 0.001, Wilcoxon rank-sum test) eCC using CG equation −12.7 mL/min QUAD group −9.5 mL/min ATV/r group (P < 0.001, Wilcoxon rank-sum test) eGFR using MDRD equation −14.1 mL/min/1.73 m2 QUAD group −9.6 mL/min/1.73 m2 ATV/r group (P < 0.001, Wilcoxon rank-sum test) |
Increases in serum creatinine and decreases in eCC and eGFR occurred in both study groups by 2 weeks, which stabilized by 8 weeks and did not change thereafter up to 96 weeks. Changes in the QUAD arm significantly greater than in the ATV/r arm |
Patents with eCC <70 mL/min excluded Few women were recruited (9.6%) |
| Rockstroh et al. [36] | 96-week analysis of GS-236-0103 |
Median changes from baseline at 96 weeks: Serum creatinine +10.6 μmol/L QUAD group +7.1 μmol/L ATV/r group (P < 0.001, Wilcoxon rank-sum test) |
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| GS-236-0102, GS-236-0103, GS-236-0104, Fisher et al. [71] | 48-week, pre-specified integrated analysis of one phase II and two phase III trials |
EVG/COBI/FTC/TDF ‘QUAD’ vs. ATV/r + FTC/TDF vs. EFV + FTC/TDF |
Median changes from baseline at 48 weeks: Serum creatinine +11.5 μmol/L QUAD group +7.1 μmol/L ATV/r group +0.9 μmol/L EFV group |
Changes first observed by 2 weeks and stabilized by 48 weeks |
Abstract presentation. No statistical comparisons quoted Short follow-up |
ATV atazanavir, ATV/r ritonavir-boosted atazanavir, eCC estimated creatinine clearance, CG cockcroft–gault, COBI cobicistat, eGFR estimated glomerular filtration rate, EFV efavirenz, EVG elvitegravir, FTC emtricitabine, MDRD Modification of Diet in Renal Disease, TDF tenofovir disoproxil fumarate