Exploratory Analysis for the Evaluation of Estimated Glomerular Filtration Rate, Cholesterol and Triglycerides after Switching from Tenofovir/Emtricitabine Atazanavir/Ritonavir (ATV/r) to Abacavir/Lamivudine ATV/r in Patients with Preserved Renal Function

Abstract

Background and Objectives:Renal toxicity due to tenofovir (TDF) has been largely described in patients with HIV infection. However, other antiretroviral drugs (such as atazanavir [ATV], especially when boosted by ritonavir, ATV/r) could perpetuate some degrees of renal impairment with or without TDF co-administration. Also, possible benefits of stopping TDF in patients without renal diseases is not well known. This study aimed at exploring evolution of renal function and lipid profile after switching from tenofovir/emtricitabine (TDF/FTC) to abacavir/lamivudine (ABC/3TC), maintaining the ATV/r component of the regimen.Methods:Patients in the Italian MASTER Cohort, who switched from TDF/FTC plus ATV/r to ABC/3TC plus ATV/r were included, provided that major renal diseases were not diagnosed before switching (i.e., baseline). Serum creatinine, estimated glomerular filtration rate (eGFR), total cholesterol, HDL and triglycerides were evaluated at baseline and at month 18 after switching.Results:126 patients were selected (80% males). Patients were mostly Italians (92%). 79% had undetectable HIV-RNA and 44% were co-infected by HBV and/or HCV. Median age at switch was 47 years (IQR 43-55). A small but significant decrease in serum creatinine [from 1.06 mg/dl (SD: 0.3) to 0.94 mg/dl (SD: 0.2); p<0.001] with an improvement in eGFR [from 86.8 ml/min (SD: 33) to 96.4 ml/min (SD: 37); p<0.001] were observed in per protocol analysis at month 18. Also ITT analysis showed a decrease in mean serum creatinine [from 1.08 mg/dl (SD: 0.35) to 0.95 mg/dl (SD: 0.24); p<0.001] with an improvement in mean eGFR [from 86.9 ml/min/1.73m2 (SD: 24.11) to 95.8 ml/min/1.73m2 (SD: 19.99); p<0.001]. Total cholesterol increased [from 188 mg/dl (SD: 42) to 206 mg/dl (SD: 44); p<0.001] but also HDL increased as well [from 46 mg/dl (SD: 14) to 54 mg/dl (SD: 19); p=0.015]. An increase in triglycerides concentration was observed [from 162 mg/dl (SD: 144) to 214 mg/dl (SD: 109); p=0.027] in per protocol analysis. Also ITT analysis showed increases of both total cholesterol [from 187 mg/dl (SD: 43.69) to 203 mg/dl (SD: 44.10); p<0.001] and HDL fraction [from 46 mg/dl (SD: 15.49) to 52 mg/dl (SD: 17.13); p=0.002] at month 18.Conclusion:This analysis reports an improvement in eGFR and an increase in total cholesterol and HDL fraction at month 18 after switching to ABC/3TC plus ATV/r. Given the fact that renal function was not significantly affected at baseline, our findings may suggest the utility of a proactive switch from TDF to ABC, when otherwise indicated, in patients who cannot avoid using a nucleoside backbone.

Raltegravir plus abacavir/lamivudine in virologically suppressed HIV-1-infected patients: 48-week results of the KIRAL study

“…Renal function parameters also remained stable during the study period, even in the subgroup of patients who switched from a regimen containing TDF ( P <0.975). These findings differ from those of other studies on switching from TDF to ABC, which reported a slight increase in eGFR [ 28 , 29 ]. A possible explanation could be that around 50% of patients were on ABC/3TC before switching, and TDF-containing regimens only accounted for 26% of patients.…”

Impact of HCV Eradication on Lipid Metabolism in HIV/HCV Coinfected Patients: Data from ICONA and HepaICONA Foundation Cohort Study

“…Of note, ABC-exposed patients also tended to show an increase in triglycerides plasmatic levels after DAA treatment, although it was not significant (Δ + 20.45 mg/dL, p = 0.008) (See Table 4 , panel D), confirming a possible unfavorable impact of this agent on lipidic metabolism [ 36 ].…”

Role of systemic inflammation scores for prediction of clinical outcomes in patients treated with atazanavir not boosted by ritonavir in the Italian MASTER cohort

“…However, an improvement of filtration rate in patients prescribed ATV/r or uATV was reported, either after switching to a regimen without TDF [19] or in patients prescribed ATV/r as a part of simplification regimens [13, 14]. Therefore, other factors than use of ATV may be involved in renal failure development.…”

“…Similarly, the expected increase in cardiovascular risk [ 15 ] was not confirmed by previous studies [ 16 – 18 ]. A recent study of the Italian MASTER cohort reported that the increased total cholesterol was balanced by the increased HDL fraction in patients prescribed ATV/r or uATV [ 19 ] and other studies observed a less impact on lipid profile in patients prescribed uATV [ 20 ].…”

“…Some degrees of acute and chronic interstitial nephritis, crystal deposition and nephrolithiasis were described when ATV/r was co-administered with other potentially nephrotoxic drugs, as tenofovir (TDF) [ 21 – 23 ]. However, an improvement of filtration rate in patients prescribed ATV/r or uATV was reported, either after switching to a regimen without TDF [ 19 ] or in patients prescribed ATV/r as a part of simplification regimens [ 13 , 14 ]. Therefore, other factors than use of ATV may be involved in renal failure development.…”