In:
HIV Medicine, Wiley, Vol. 19, No. 3 ( 2018-03), p. 227-237
Abstract:
Studies evaluating the efficacy and safety of the fixed‐dose combination ledipasvir ( LDV )/sofosbuvir ( SOF ) in patients coinfected with HIV ‐1 and hepatitis C virus ( HCV ) have mainly included treatment‐naïve patients without cirrhosis. We aimed to evaluate the efficacy and safety of this combination in treatment‐experienced patients with and without cirrhosis. Methods We conducted a multicentre, open‐label, double‐arm, nonrandomized study in patients coinfected with HIV ‐1 and HCV genotype 1 with and without cirrhosis, who had good viral suppression on their antiretroviral regimens. All patients were pretreated with a first‐generation NS 3/4A protease inhibitor ( PI ) plus pegylated interferon/ribavirin. Patients received a fixed‐dose combination of LDV / SOF for 12 weeks, or for 24 weeks if cirrhosis was present. The primary endpoint was a sustained virological response ( SVR ) 12 weeks after the end of therapy. Secondary endpoints included safety, pharmacokinetics and patient‐reported outcomes. Results Of the 68 patients enrolled, 39.7% had cirrhosis. Sixty‐five patients [95.6%; 95% confidence interval ( CI ): 87.6–99.1%; P 〈 0.0001] achieved an SVR , with similar rates of SVR in those with and without cirrhosis. Tolerance was satisfactory, with mainly grade 1 or 2 adverse events. Among patient‐reported outcomes, only fatigue significantly decreased at the end of treatment compared with baseline [odds ratio ( OR ): 0.36; 95% CI : 0.14–0.96; P = 0.04]. Mean tenofovir area under the plasma concentration–time curve ( AUC ) at week 4 was high, with mean ± SD AUC variation between baseline and week 4 higher in cirrhotic than in noncirrhotic patients (3261.57 ± 1920.47 ng/mL vs. 1576.15 ± 911.97 ng/mL, respectively; P = 0.03). Mild proteinuria (54.4%), hypophosphataemia (50.0%), blood bicarbonate decrease (29.4%) and hypokalaemia (13.2%) were reported. The serum creatinine level was not modified. Conclusions LDV / SOF provided a high SVR rate in PI ‐experienced subjects coinfected with HCV genotype 1 and HIV ‐1, including patients with cirrhosis.
Type of Medium:
Online Resource
ISSN:
1464-2662
,
1468-1293
DOI:
10.1111/hiv.2018.19.issue-3
Language:
English
Publisher:
Wiley
Publication Date:
2018
detail.hit.zdb_id:
2020341-X
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