Raltegravir Pharmacokinetics in Patients on Asunaprevir-Daclatasvir.

Raltegravir pharmacokinetics was studied in 20 patients included in the ANRS HC30 QUADRIH Study before and after addition of anti-hepatitis C virus (anti-HCV) quadritherapy, including pegylated-interferon-ribavirin and asunaprevir plus daclatasvir. Raltegravir pharmacokinetic parameters remained unchanged whether administered on or off anti-HCV therapy. In addition, concentrations of raltegravir, asunaprevir, and daclatasvir were not affected by liver cirrhosis. These data suggest that in human immunodeficiency virus (HIV)-HCV-coinfected patients, whether cirrhotic or not, asunaprevir and daclatasvir could be administered safely with raltegravir.

Telaprevir for HIV/hepatitis C virus-coinfected patients failing treatment with pegylated interferon/ribavirin (ANRS HC26 TelapreVIH): an open-label, single-arm, phase 2 trial.

BACKGROUND: Retreatment with pegylated interferon (peg-IFN) and ribavirin (RBV) results in poor sustained virological response (SVR) rates in human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients. There are limited data regarding the use of telaprevir plus peg-IFN/RBV in this population. METHODS: HIV type 1-infected patients who previously failed ≥12 weeks of peg-IFN/RBV for HCV genotype 1 coinfection were enrolled in a single-arm, phase 2 trial. Patients with cirrhosis and previous null response were excluded. Authorized antiretrovirals were tenofovir, emtricitabine, efavirenz, atazanavir, and raltegravir. All patients received peg-IFN alfa-2a (180 µg/week) plus RBV (1000-1200 mg/day) for 4 weeks, followed by telaprevir (750 mg or 1125 mg every 8 hours with efavirenz) plus peg-IFN/RBV for 12 weeks and peg-IFN/RBV for 32-56 weeks according to virological response at week 8. The primary endpoint was the SVR rate at 24 weeks after the end of treatment (SVR24). RESULTS: Sixty-nine patients started treatment; SVR24 was achieved in 55 (80% [95% confidence interval, 68%-88%). SVR24 was not influenced by baseline fibrosis stage, IL28B genotype, antiretroviral regimen, HCV subtype, CD4 cell count, previous response to HCV treatment, HCV RNA level, or HCV RNA decline at week 4. HCV treatment was discontinued for adverse events (AEs) in 20% of patients, including cutaneous (4%), psychiatric (4%), hematological (6%), and other AEs (6%). Peg-IFN or RBV dose reduction was required in 23% and 43% of patients, respectively. Seventy percent of patients required erythropoietin, blood transfusions, or RBV dose reduction for anemia. Two patients died during the study. No HIV breakthrough was observed. CONCLUSIONS: Despite a high discontinuation rate related to toxicity, a substantial proportion of treatment-experienced HIV-coinfected patients achieved SVR24 with a telaprevir-based regimen. Clinical Trials Registration. NCT01332955.

Telaprevir enhances ribavirin-induced anaemia through renal function impairment.

BACKGROUND: Alterations in renal function have been described with telaprevir (TVR). We examined the relationship between ribavirin (RBV) trough concentration (C), estimated glomerular filtration rate (eGFR) and severe anaemia, before and after TVR introduction in HIV-HCV-coinfected patients included in ANRS HC26 TelapreVIH study. METHODS: 69 HIV-HCV genotype-1 coinfected patients received 4 weeks of pegylated interferon (PEG-IFN)-α2a/RBV, followed by 12 weeks of TVR/PEG-IFN/RBV, then 32 to 56 weeks of PEG-IFN/RBV. RBV C was determined at week (W)4, W8 and W20/24. eGFR was estimated by the Modification of the Diet in Renal Disease (MDRD) equation. Severe anaemia was defined as haemoglobin <70 g/l, RBV dose reduction, prescription of erythropoietin or blood transfusion. RESULTS: 67 patients were analysed. eGFR remained normal between baseline (97.9 ml/min) and W4 (103.4 ml/min), declined to 86.3 ml/min at W8 (P<0.0001), stabilized until W16 and increased back to baseline level at W20 (98.4 ml/min). RBV C increased from 1.88 mg/l at W4 to 2.88 mg/l at W8 (P<0.0001), then decreased to 2.73 mg/l at week 20/24 (P=0.015). An inverse correlation was observed between W8 eGFR and W8 RBV C (r2=0.429; P=0.0005). RBV C≥3 mg/l was observed in 12% of patients at W4, 45% at W8 (P<0.0001) and 38% at W20/24 (P=0.0005). Severe anaemia was observed in 23.9% of patients at W4 and 45.3% at W8. RBV C≥3 mg/l at W8 (OR 7.7 [95% CI 2.2, 27.4]) and baseline haemoglobin <150 g/l (OR 6.4 [1.7, 23.8]) were independently associated with W8 severe anaemia. CONCLUSIONS: Association of TVR to PEG-IFN/RBV was associated with a decrease in eGFR and increase in RBV C, leading to severe anaemia in 45% of patients.