Effects of a switch from tenofovir‐ to abacavir‐based antiretroviral therapy, with or without atazanavir, on renal function

Abstract

IntroductionTenofovir disoproxil fumarate (TDF)–associated renal dysfunction may abate when TDF is replaced with abacavir (ABC). The extent to which the third drug atazanavir contributes to renal dysfunction is unclear.MethodsA retrospective analysis was conducted on adults who had plasma viral load (pVL)<200 copies/mL for≥six months while receiving TDF/lamivudine (3TC) – or TDF/emtricitabine (FTC)–based antiretroviral therapy (ART), then switched to ABC/3TC while retaining the third drug in the ART regimen. CD4, pVL, creatinine, estimated glomerular filtration rate (eGFR), serum phosphorus, urine albumin to creatinine ratio and serum lipids were compared between pre-switch baseline and 3, 6 and 12 months after the switch to ABC.ResultsA total of 286 patients switched from TDF to ABC between 2004 and 2014: 232 (81%) male, median age 48 years (interquartile range (IQR) 42, 56). The third drug was atazanavir (± ritonavir) in 141 (49%) cases. The pVL was<50 copies/mL in 93 to 96% at all time points. Median serum creatinine was 93 µmol/L (IQR 80–111) at baseline and decreased to 88 µmol/L (IQR 78–98) at 12 months after the switch to ABC. Median eGFR increased from 74 (IQR 60–88) mL/min at baseline to 80 mL/min (IQR 69–89) at 12 months. Results were not significantly different between patients on atazanavir versus those on another third drug.ConclusionsViral suppression was maintained among patients who switched from TDF/3TC or TDF/FTC to ABC/3TC. Serum creatinine and eGFR improved up to 12 months after switching to ABC/3TC, irrespective of whether or not patients were also receiving atazanavir±ritonavir.

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.…”

Switching to abacavir versus use of a nucleoside‐sparing dual regimen for HIV‐infected patients with tenofovir‐associated renal toxicity

“…However, the ASSURE (A Simplification Study of Unboosted Reyataz with Epzicom) trial showed a nonsignificant improvement in eGFR after switching from TDF to abacavir (+0.8 vs. À1.3 in those who continued TDF), but significantly better evolution in tubular proteinuria [21]. A significant improvement in eGFR, albuminuria and phosphataemia was also found in a recent study where TDF was switched to abacavir, regardless of whether or not patients continued with atazanavir [22]. These differences in eGFR evolution were mainly based on different baseline patient characteristics, because the studies included patients without renal involvement.…”

Abacavir usage patterns and hypersensitivity reactions in the EuroSIDA cohort

“…Unexpectedly, higher ABC utilization was associated with CKD and higher D:A:D CKD risk scores, although this could be attributed to confounding by indication. Use of tenofovir has been linked to kidney disease [24] and individuals on tenofovir with decreasing renal function are likely to discontinue tenofovir [25] and be switched to ABC [26], a drug with no reported adverse effect on renal function. Changes over time and within regions in use of abacavir probably reflect marketing and availability of abacavir.…”