RESUMO
BACKGROUND: Twelve weeks of the pangenotypic direct-acting antiviral (DAA) combination sofosbuvir/velpatasvir (SOF/VEL) was highly efficient in patients with hepatitis C virus (HCV) genotype 3 (GT3) infection in the ASTRAL-3 approval study. However, presence of resistance-associated substitutions (RASs) in the HCV nonstructural protein 5A (NS5A) was associated with lower treatment response. AIM: To assess the efficacy and safety of SOF/VEL ± ribavirin (RBV) and the impact of NS5A RASs and RBV use on treatment outcome in HCV GT3 infection in a real-world setting. METHODS: In this multicentre cohort study, GT3 patients from ten treatment centres across Germany were included. Sustained virological response was assessed 12 weeks after end-of-treatment (SVR12) in modified intention-to-treat (mITT) and per-protocol analysis (PP). NS5A RASs were tested by population-based sequencing. RESULTS: A total of 293 GT3 patients were included. The median age was 48 years, 70% were male, 25.3% were cirrhotic, 9.2% were HCV/HIV co-infected and 21.8% were treatment-experienced, including 4.1% with DAA experience. Baseline NS5A RASs (Y93H, A30K, L31M) were detected in 11.2%. RBV was added in 5% of noncirrhotic and 58.9% of cirrhotic patients, respectively. SVR12 rates for SOF/VEL±RBV were 95.9% (mITT) and 99.5% (PP), respectively. Only 1 virological relapse occurred in a cirrhotic patient previously treated with SOF/RBV. No treatment-related major adverse events occurred. CONCLUSION: Twelve weeks of SOL/VEL±RBV was safe and highly efficient in HCV GT3 across a diverse patient population. Baseline NS5A RASs were rarely observed and presence did not seem to impact SVR, regardless of the use of RBV.
Assuntos
Carbamatos/administração & dosagem , Farmacorresistência Viral , Hepatite C/tratamento farmacológico , Compostos Heterocíclicos de 4 ou mais Anéis/administração & dosagem , Sofosbuvir/administração & dosagem , Adolescente , Adulto , Idoso , Antivirais/administração & dosagem , Estudos de Coortes , Farmacorresistência Viral/efeitos dos fármacos , Farmacorresistência Viral/genética , Substituição de Medicamentos/métodos , Quimioterapia Combinada , Feminino , Genótipo , Alemanha/epidemiologia , Hepacivirus/genética , Hepatite C/epidemiologia , Hepatite C/genética , Hepatite C/virologia , Humanos , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/epidemiologia , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade , Resposta Viral Sustentada , Resultado do Tratamento , Proteínas não Estruturais Virais/genética , Adulto JovemRESUMO
Albumin excretion, Analysis of urinary proteins by polyacrylamide gel electrophoresis (PAGE), and clinical evaluation were performed in 90 HIV-infected patients to assess subclinical renal involvement in HIV infection. Thirteen percent of all patients showed an albumin excretion > 20 mg/liter. Seven of four homosexual patients had albuminuria. Albuminuria occurred exclusively with T4 cell counts below 200/mm3. Polyacrylamide gel electrophoresis indicated glomerular lesions and showed no tubular proteinuria in patients with increased albumin excretion. It is concluded that subclinical renal involvement is not uncommon in HIV infection with T4 cell counts > 200/mm3. HIV-associated nephropathy and heroin-associated nephropathy may not be the main causes of renal involvement. In some cases, opportunistic viral infections may be the cause of microalbuminuria.
