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Kidney Function Improves After Switch From LPV or ATV to DRV
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HIV Drug Therapy, Glasgow 2016
Mark Mascolini
Kidney function assessed as estimated glomerular filtration rate (eGFR) stopped falling and started rising after a switch from lopinavir/ritonavir (LPV/r) or atazanavir/ritonavir (ATV/r) to darunavir/ritonavir (DRV/r) in a 1700-person analysis of the UK CHIC cohort [1]. This improving course occurred only in people taking tenofovir disoproxil fumarate (TDF) with their first protease inhibitor (PI), but improvement occurred in people who kept taking TDF with DRV/r.
Treatment with TDF, LPV, or ATV is linked to new chronic kidney disease (CKD) or worsening CKD. Whether the associations with LPV or ATV indicate a PI class effect is unknown. To answer that question, UK CHIC investigators conducted this study of cohort members switching from LPV or ATV to DRV.
The analysis focused on cohort members who had taken LPV or ATV for at least 6 months and had two serum creatinine measures before and after the switch to DRV. The investigators calculated eGFR with the CKD-EPI equation. They determined the impact of the PI switch in models adjusted for age, sex, ethnicity, TDF use, CD4 count, and viral load.
The study group included 1015 people switching from LPV and 676 switching from ATV. Almost 80% in both groups were men, two thirds were white, and one quarter were black. Median age measured 45 years in both groups. Overall median CD4 count measured 520 (interquartile range 362 to 726), and 77% had a viral load at or below 50 copies. At the switch 6.5% in the LPV group and 12.9% in the ATV group had an eGFR below 60 mL/min.
In the years before the PI switch, eGFR was falling significantly in the LPV group (average slope -0.51 per year, 95% confidence interval -0.90 to -0.21) and in the ATV group (average -0.97 per year, 95% CI -1.35 to -0.59). The PI swap to DRV coincided with a rebound in eGFR in the LPV group (average +0.43 per year, 95% CI 0.14 to 0.71) and the ATV group (average +1.06 per year, 95% CI 0.69 to 1.44). Among people with more rapid eGFR drops or an eGFR below 60 mL/min at the switch, eGFR declines were more rapid before the switch and eGFR gains steeper after the switch. For example, average per-year changes before and after the switch in ATV users with eGFR below 60 mL/min at the switch were -6.59 and +2.68 (P < 0.001). Respective average changes in LPV users below 60 mL/min at the switch were -2.77 and +2.13 (P < 0.001).
Declining and rebounding eGFR were significant in people taking TDF with their initial PI but not in those without TDF in their initial PI regimen. Among people taking TDF before the switch and keeping TDF in their postswitch regimen, average per-year changes in eGFR from before to after the switch were significant in both the ATV group (from -0.42 to +0.38, P = 0.006) and the LPV group (from -0.44 to +0.52, P < 0.001).
The UK CHIC team noted that their analysis is limited by lack of information on why people switched their PI, by the possibility that falling eGFR could reflect "indolent eGFR decline or acute renal injury with incomplete recovery," and by the residual confounding possible in any observational study. With those limitations in mind, the researchers proposed that "in individuals with or at risk of renal dysfunction, DRV may be the PI of choice, especially if continued use of TDF is required."
Reference
1. Jose S, Nelson M, Phillips A, et al. Improved kidney function in patients who switch their protease inhibitor from atazanavir or lopinavir to darunavir. HIV Drug Therapy, Glasgow 2016. October 23-26, 2016. Abstract P218.
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