Treatment outcomes with telaprevir-based therapy for HIV/hepatitis C coinfected patients are comparable with hepatitis C monoinfected patients

Abstract

To the Editor: Hepatitis C virus (HCV) infection is an important cause of morbidity and mortality among individuals living with HIV (1). Before the introduction of direct-acting antivirals (DAAs), pegylated interferon (peg-IFN) and ribavirin (RBV) were standard of care for coinfected patients with dismal sustained virological response (SVR) rates of <30% (2,3). Telaprevir (TVR), an NS3/4A protease inhibitor, was a first-generation DAA approved for HCV treatment in Canada, in November 2012. In randomized trials, the rate of SVR to TVR/peg-IFN/RBV was 65% to 75% in monoinfected patients and similar in coinfected patients (4-8). Few studies have reported treatment outcomes of TVR-based therapy outside of clinical trials. Our objective was to compare clinical outcomes of HCV-monoinfected and HIV-HCV coinfected patients treated with TVR-based triple therapy at a regional referral centre in Alberta. Patients who initiated TVR/pegIFN/RBV combination therapy from June 2011 to December 2013, were included in the study. Patients were treated according to Canadian guidelines for HCV treatment (9,10). All patients with HCV genotype 1 were eligible for therapy and were treated at the discretion of their HCV care provider. Demographic, clinical and laboratory data were collected at baseline and during therapy. Parameters of interest included HIV-coinfection, body mass index (BMI), Child-Pugh classification, previous injection drug use, haemophilia, liver transplantation, hepatitis B coinfection and previous HCV treatment. Fibrosis was determined using transient elastography by FibroScan (Echosens, France) with the following parameters: F0 to F1 ≤7.0, F2 7.1 to 9.4, F3 9.5 to 12.4, F4 (cirrhosis) ≥12.5 (11). Where applicable, HIV viral load and CD4+ T cell count were collected. Severe treatment-related anemia and thrombocytopenia were defined as nadir of hemoglobin ≤80 g/L and platelet count ≤50×109, respectively. Treatment response was determined using established definitions according to Canadian guidelines (9). Patients lost to follow-up were considered to have virological failure. In total, 103 patients received TVR at our clinics (Table 1). This included 13 (12.6%) HIV-HCV coinfected patients and seven (6.7%) patients who experienced recurrent HCV after liver transplantation. The median age at treatment onset was 56 years (interquartile range [IQR]: 51 to 59 years); 72% of patients were male and 86% were Caucasian. One-third (37%) of patients reported a history of injection drug use, nine (10%) had hemophilia and three (3%) were HCVhepatitis B virus coinfected. The median BMI was 26.8 kg/m2 (IQR 24.0 kg/m2 to 30.5 kg/m2). Forty-seven percent (n=45) of patients had been previously treated with pegIFN-RBV and 13% (n=12) were previous null responders. Most patients were HCV genotype 1a and IL28B non-CC genotype (71% and 70%, respectively). The majority (60%) of patients had advanced fibrosis or cirrhosis (F3 or F4). One patient had decompensated Child-Pugh B cirrhosis. HCV-HIV coinfected patients did not differ significantly with respect to previous anti-HCV therapy, HCV genotype subtype, interleukin (IL)28B genotype or degree of fibrosis. Coinfected patients were more likely to report injection drug use (P=0.05) and to have hemophilia (P=0.03). Most (92%) HIV coinfected patients had undetectable HIV RNA while receiving antiretroviral therapy, with a median baseline CD4 count of 490 cells/mm3 (IQR 250 cells/mm3 to 639 cells/mm3). Most (85%) required adjustment of their antiretroviral regimen before TVR initiation. Integrase-based antiretroviral therapy was the most commonly (77%) used regimen. The overall rate of SVR in our cohort was 66% (Table 2). The rate of SVR among HIV-HCV coinfected patients was 62% (eight of 13). Patients with cirrhosis and previous null responders had a lower SVR rate (54% and 42%, respectively). Fifty-seven percent (four of seven) of post-liver transplant recipients achieved SVR. Outcomes for postliver transplant patients have been previously reported (12). Among treatment failures, discontinuation due to adverse events was the most common (20%), followed by virological relapse (15%). Five (5%) patients discontinued therapy due to hepatic decompensation. Two (2%) patients were lost to follow-up. Two (2%) patients died; one patient died due to drug and alcohol intoxication while on therapy. The other patient had Child-Pugh B cirrhosis at baseline and died from complications of decompensated cirrhosis. The most commonly reported side effects were fatigue (65%), rash (68%), mood symptoms (42%), anorectal symptoms (43%) and infections (17%). Severe anemia occurred in 15% of participants and warranted red blood cell transfusion or erythropoietin in 11% and 2%, respectively. Severe thrombocytopenia occurred in 24% of participants. Most (57%) patients required RBV dose reduction. Comparing HCV monoinfected with HIV coinfected patients, there was no significant difference with regard to SVR (67% versus 62%, P=0.76). There was no difference between monoinfected and coinfected patients in treatment discontinuation due to adverse events (20% versus 15%; P=1.00) or virological relapse (13% versus 23%; P=0.40). One patient with HIV coinfection discontinued therapy due to hepatic decompensation, but nevertheless achieved SVR. There were no deaths among HIV-coinfected patients. Patients with HIV coinfection were more likely to have infections (12% versus 48%; P≤0.01), severe anemia (11% versus 38%; P=0.02) and to require peg-IFN dose adjustment (6% versus 46%; P≤0.01). In HIVcoinfected patients, infectious complications consisted of cellulitis (n=2), sepsis (n=1), gastroenteritis (n=1) and urinary tract infections (n=1). All HIV-coinfected patients maintained undetectable HIV RNA while receiving therapy. In a bivariate analysis, variables associated with increased rate of SVR included lower BMI (26.0 kg/m2 [IQR 24.0 kg/m2 to 29.1 kg/m2] versus 29.1 kg/m2 [IQR 26.6 kg/m2 to 32.0 kg/m2]; P=0.05), IL28B genotype CC (37% versus 12%; P=0.02) and cirrhosis (37% versus 60%; P=0.03). In a multivariate analysis, only fibrosis class (F0 to F2 versus F3 to F4; adjusted OR 0.34 [95% CI 0.12 to 0.99]; P=0.05) remained significantly associated with SVR. HIV status, a history of injection drug use and previous response to peg-IFN therapy did not predict SVR. There have been few reports of the effectiveness of TVR-based therapy in HIV-coinfected patients outside of clinical trials. In our study, the overall SVR was 67% in HCV-monoinfected patients and 62% in coinfected patients. This is comparable with clinical trials, despite a higher percentage of patients with cirrhosis (45%) in our cohort (4-6). Lower BMI, IL28B CC genotype and degree of fibrosis were associated with increased probability of SVR, although in multivariate analysis, only degree of fibrosis remained a significant predictor of SVR. Additional negative predictors of SVR with TVR-based therapy included African American race and previous treatment response (13). We also demonstrated that HIV coinfection is not a negative predictor of SVR. This was consistent with trials involving second-generation DAAs such as ledipasvir and sofosbuvir. Data from patients with HCV monoinfection treated