Antiviral therapy for HCV in hemophilia A patients with HIV-1 co-infection

Abstract

Anti-hepatitis C virus (HCV) treatment for human immunodeficiency virus (HIV)/HCV co-positive patients with hemophilia A presents numerous problems in terms of safety and effectiveness. The emergence of direct-acting antiviral (DAA) regimens has led to tremendous changes in the management of HIV/HCV co-infection over the past few years, but the application of DAA in patients with hemophilia complicated with HIV/HCV co-infection has rarely been reported. We retrospectively analyzed the clinical course and outcome of hemophilia A patients with HIV/HCV co-infection receiving DAA with a focus on the virological response, changes in cluster of differentiation 4 lymphocyte (CD4) count, side effects, and impact on bleeding before and after DAA therapy. A total of 12 hemophilia A patients with HIV/HCV co-infection were included, 9 of which were severe. All the patients were in stable states with CD4 counts >200/mm3 and plasma HIV ribonucleic acid (RNA) suppressed (<40IU/mL) while taking the antiretroviral regimen. Majority of the patients (n = 9, 75.0%) were infected with HCV genotype (GT) 1b, while 2 and 1 was infected with HCV GT 2i and HCV GT 3, respectively. After 12 weeks of DAA treatment, 11 patients (91.7%) obtained sustained virologic response within 24 weeks of discontinuation of treatment (SVR24), except 1 patient who was treated with sofosbuvir (SOF) + pegylated interferon + ribavirin (PR), which was then switched to daclatasvir (DCV) + asunaprevir (ASV) for 12 weeks; this patient then achieved SVR24. During DAA treatment, HIV RNA in all the patients was constantly suppressed, while CD4 counts showed no obvious change. The most common treatment-emergent adverse events were weakness and loss of appetite (generally mild). There was no evidence of an increased tendency of bleeding, and changes in response to replacement. DAA therapy offered a safe and well-tolerated management strategy for HIV/HCV co-infected patients with hemophilia A. An awareness of the potential drug-drug interactions (DDI) between DAA and combination antiretroviral therapy (cART) by clinicians is important for optimal management of co-infected patients. Abbreviations: 3TC = lamivudine, AIDS = acquired immune deficiency syndrome, ASV = asunaprevir, cART = combination antiretroviral therapy, CD4 = cluster of differentiation 4, DAA = direct-acting antiviral regimen, DCV = daclatasvir, DDI = drug-drug interactions, EFV = efavirenz, EOTR = end of treatment, FTC = emtritabine, GT = genotype, HCV = hepatitis C virus, HIV = human immunodeficiency virus, NNRTI = non-nucleoside reverse transcriptase inhibitors, NS5A = non-structural protein 5A, NS5B = nonstructural protein 5B, PI = protease inhibitors, PR = pegylated interferon + ribavirin, RAL = raltegravir, RBV = ribavirin, RNA = ribonucleic acid, RT-PCR = reverse transcriptase- polymerase chain reaction, SHAPHC = Shanghai Public Health Clinical Center, SOF = sofosbuvir, SVR = sustained virological response, SVR12 = sustained virological response within 12 weeks of discontinuation of treatment, SVR24 = sustained virological response within 24 weeks of discontinuation of treatment, TDF = tenofovir, Y = yes, VEL = velpatasvir, ZDV = zidovudine.