Abstract
IntroductionConcomitant use of ledipasvir and boosted protease inhibitors (PIs) may increase the risk of tenofovir (TDF) nephrotoxicity, since both these drugs increase TDF levels. Our aim was to evaluate glomerular filtration rate (eGFR) evolution during HCV treatment with sofosbuvir/ledipasvir (SOF/LDV) in HCV/HIV coinfected patients, according to their antiretroviral treatment (ARV).MethodsObservational prospective study of HCV/HIV coinfected patients treated with SOF/LDV. eGFR evolution was evaluated during and 12 weeks after HCV treatment. Patients were categorized in three groups based on ARV regimen: non TDF, non-boosted TDF and TDF + boosted PI.ResultsWe included 273 patients: 145 were receiving a non-TDF regimen, 78 a non-boosted TDF scheme and 50 were receiving TDF + boosted PI. We observed a statistically significant decrease in eGFR during treatment in all groups (non TDF p = 0.03, 95%CI [0.23–3.86], non-boosted TDF p < 0.01, 95%CI [3.36–7.44], TDF + PI p = 0.01, 95%CI [1.09–7.53]). The decrease was more pronounced in those receiving unboosted TDF (− 5.40 ml/min/1.73m2), but differences in eGFR decrease between the three groups were small and not statistically different (p = 0.06). eGFR decrease was greater in patients treated for 24 weeks (p = 0.009) and in cirrhotic patients (p = 0.036). At the end of follow up a recovery of eGFR was observed in all groups.ConclusionWe observed a significant decrease in eGFR during treatment in all study groups, that was small and reversible after SOF/LDV discontinuation. TDF was not associated with an increase in renal toxicity.
Highlights
Concomitant use of ledipasvir and boosted protease inhibitors (PIs) may increase the risk of tenofovir (TDF) nephrotoxicity, since both these drugs increase TDF levels
According to the World Health Organization (WHO), 2–15% of the people infected by the human immunodeficiency virus (HIV) are coinfected with hepatitis C virus (HCV), and this percentage goes up to 90% in those who acquired the infection through intravenous drug use [1]
All the 273 HCV/HIV patients were receiving antiretroviral medication: 53.1% (n = 145) received a non-TDF regimen, 28.6% (n = 78) used an unboosted TDF scheme and TDF plus boosted PI was administered in 18.3% (n = 50)
Summary
Concomitant use of ledipasvir and boosted protease inhibitors (PIs) may increase the risk of tenofovir (TDF) nephrotoxicity, since both these drugs increase TDF levels. Our aim was to evaluate glomerular filtration rate (eGFR) evolution during HCV treatment with sofosbuvir/ledipasvir (SOF/LDV) in HCV/HIV coinfected patients, according to their antiretroviral treatment (ARV). Liver disease is currently one of the leading causes of morbidity and mortality in HIV infected people [2, 3] and HIV coinfected patients seem to have a faster progression to cirrhosis, a higher rate of liver decompensation and liver death and a lower response to HCV therapy [4–6]. With the advent of direct acting antivirals (DAAs), the sustained virologic response (SVR) rates in mono and HIV co-infected patients are similar. With these agents, high cure rates are achieved in the co-infected population, with excellent tolerability and convenient posology [8, 9]. Clinicians are advised to check possible DDIs between the HCV DAAs and other chronic medication, using up to date resources such as the one found at http://www.hep-druginteractions.org [8]
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