Treatment intensification with boceprevir in HIV-positive patients with acute HCV-genotype 1 infection at high risk for treatment failure.

BACKGROUND: According to current guidelines, the universal use of direct-acting antiviral agents in HIV-positive patients with acute hepatitis C (AHC) is not recommended. We aimed to evaluate the concept of treatment intensification with boceprevir (BOC) in HIV-positive patients with HCV-genotype 1 AHC (HIV/AHC-GT1) at high risk for failure to pegylated interferon/ribavirin therapy (PEGIFN/RBV). METHODS: Nineteen consecutive HIV-positive patients with HIV/AHC-GT1 who underwent antiviral therapy were studied retrospectively. Patients were treated with PEGIFN/RBV for 24 or 48 weeks, depending on rapid virologic response (RVR; undetectable HCV-RNA at treatment week [W] 4). Patients without complete early virologic response (cEVR; undetectable HCV-RNA at W 12) were offered treatment intensification with BOC at W 12, resulting in 36 weeks of BOC/PEGIFN/RBV triple therapy (total treatment duration: 48 weeks). RESULTS: Thirty-seven percent (7/19) of patients had an RVR and 74 % (14/19) of patients had a cEVR. BOC was used in four out of five patients who did not achieve cEVR and one patient elected to proceed with PEGIFN/RBV. Sustained virologic response (SVR; undetectable HCV-RNA 24 weeks after the end of treatment) rates were 100 % (14/14) among patients with cEVR treated with PEGIFN/RBV and 75 % (3/4) among patients without cEVR receiving BOC add-on. The patient without cEVR who preferred to continue with PEGIFN/RBV did not achieve SVR. Thus, the overall SVR rate was 89 % (17/19) in intention to treat analysis. CONCLUSIONS: BOC add-on in selected HIV/AHC-GT1 resulted in a high overall SVR rate. If 2nd generation direct-acting antiviral agents (DAAs) are not available, treatment intensification with BOC can be considered in HIV/AHC-GT1 at high risk for failure to PEGIFN/RBV.

Response-guided boceprevir-based triple therapy in HIV/HCV-coinfected patients: the HIVCOBOC-RGT study.

BACKGROUND: The HIVCOBOC-RGT study (NCT01925183) was the first study to evaluate response-guided shortening of the duration of boceprevir (BOC)-based triple therapy in human immunodeficiency virus (HIV)/hepatitis C virus genotype 1-coinfected patients (HIV/HCV-GT1). METHODS: After 4 weeks of pegylated interferon-α-2a/ribavirin (PEGIFN/RBV) lead-in, patients with target-not-detectable HCV-RNA at week 8 (rapid virologic response; LI4W-W8UTND) received 24 weeks of BOC/PEGIFN/RBV (total: 28 weeks [W28]). Patients with target-detectable HCV-RNA at week 8 received 44 weeks of BOC/PEGIFN/RBV (total: 48 weeks [W48]). RESULTS: Fourteen patients (67%) had LI4W-W8UTND and were eligible for the shortened W28 arm, while 7 (33%) patients were allocated to the W48 arm. No breakthrough or relapse occurred in the W28 arm, resulting in a sustained virologic response (SVR12TND) rate of 100% (12/12). In the W48 arm, the SVR12TND was 50% (3/6), with 3 patients meeting the futility rule at treatment week 12. The preliminary overall SVR12TND rate was 83% (15/18). Serious adverse events were observed in 5 (24%) patients, with 2 (10%) patients requiring surgical treatment of abscesses. CONCLUSIONS: The majority of HIV/HCV-GT1 were eligible for response-guided shortening of treatment duration to W28 and all of these patients had a SVR12TND. If second-generation direct-acting antivirals are not available, W28 of BOC-based triple therapy may be recommended.

Revisiting liver disease progression in HIV/HCV-coinfected patients: the influence of vitamin D, insulin resistance, immune status, IL28B and PNPLA3.

BACKGROUND & AIMS: To perform a comprehensive study on independent modulators of liver fibrosis progression and determinants of portal pressure considering immune status, insulin resistance (IR), serum 25-hydroxyvitamin D (25(OH)D) levels, genetic variants of patatin-like phospholipase domain-containing protein 3 (PNPLA3) and interleukin 28B (IL28B) in a thoroughly documented cohort of HIV/hepatitis C-coinfected (HIV/HCV) patients. PATIENTS & METHODS: 25(OH)D deficiency (25(OH)DDEF), IR and low CD4(+) T-lymphocyte nadir (lowCD4NAD) were defined as 25(OH)D <20 ng × ml(-1) , HOMA-IR >2 and CD4nadir <200 cells × µl(-1) respectively. Liver fibrosis progression rate (FPR) was calculated as METAVIR F units divided by the number of years since HCV infection. Patients with a FPR > median FPR were assigned to the highFPR group. RESULTS: Among 86 HIV/HCV, the median FPR was 0.167 units × years(-1) . While the prevalence of prior alcohol abuse, lowCD4NAD and 25(OH)DDEF was higher among highFPR patients, the prevalence of IR was comparable. The association between 25(OH)DDEF and FPR was confirmed in a subgroup of patients with METAVIR stage F0/F1/F2 in which 25(OH)D levels are not affected by the severity of liver disease. The distribution of IL28B C/C and PNPLA3 non-C/C was similar, while PNPLA3 G/G was exclusively observed in highFPR patients. LowCD4NAD (OR: 2.95; 95% CI: 1.05-8.24; P = 0.039) and 25(OH)DDEF (OR: 5.62; 95% CI: 2.05-15.38; P = 0.001) were independently associated with highFPR and showed an additive effect. Portal pressure correlated with prior alcohol abuse, HCV-genotype 3, CD4(+) nadir and 25(OH)D levels. CONCLUSIONS: Two potentially modifiable factors, CD4(+) nadir and 25(OH)D levels, were both independent modulators of liver fibrosis progression and determinants of portal pressure. Further studies are warranted to assess the relevance of PNPLA3 for FPR in HIV/HCV.

New reliability criteria for transient elastography increase the number of accurate measurements for screening of cirrhosis and portal hypertension.

BACKGROUND & AIMS: Transient elastography (TE) can non-invasively diagnose cirrhosis and portal hypertension (PHT). New TE reliability criteria suggest classifying measurements as very reliable (IQR/M < 0.1), reliable (IQR<0.3 or >0.3, if TE < 7.1 kPa) and poorly reliable (IQR/M > 0.3, if TE > 7.1 kPa). Compare traditional (reliable: success rate >60% + IQR/M ≤ 0.30) and new TE quality criteria (accurate: very reliable + reliable) regarding their diagnostic accuracy for cirrhosis and PHT and to identify potential confounders (age, aetiology, necroinflammatory activity, steatosis, siderosis, cholestasis, aminotransferases) of TE performance. METHODS: Patients undergoing simultaneous measurements of TE, portal pressure (hepatic venous pressure gradient, HVPG) and liver biopsy were analysed. RESULTS: Among 226 patients (48.7 ± 13.1 years, 74.7% male, 75.7% viral aetiology, 57% F3/F4), traditional TE quality criteria identified 71.6% reliable measurements, while new criteria yielded in 83.2% accurate results. Reliable TE values according to both criteria significantly correlated with fibrosis stage (r = 0.648 vs. r = 0.636) and HVPG (r = 0.836 vs. r = 0.846). Diagnostic accuracy for cirrhosis (cut-off >14.5 kPa) was 76.5% (AUC: 0.863) and 75.0% (AUC: 0.852) for traditional and new TE criteria, respectively, while for predicting HVPG ≥ 10 mmHg (>16.1 kPa), the accuracies were 88.9% (AUC: 0.957) and 89.8% (AUC: 0.962). New TE criteria allowed a better discrimination of reliable and non-reliable results for prediction of fibrosis and CSPH. Only aetiology and aminotransferases were independent confounders of the correlation of TE and fibrosis stage, while no confounder affected the correlation of TE and HVPG. CONCLUSIONS: New reliability criteria for TE measurements increase the number of patients with accurate measurements without affecting diagnostic performance for detecting cirrhosis and portal hypertension. Aetiology of liver disease and aminotransferases should be considered when assessing liver fibrosis by TE.

Therapeutic potential of and treatment with boceprevir/telaprevir-based triple-therapy in HIV/chronic hepatitis C co-infected patients in a real-world setting.

The aim of this study was to assess the therapeutic potential of telaprevir (TPV)/boceprevir (BOC)-based triple-therapy in a complete cohort of HIV/chronic hepatitis C co-infected patients (HIV/HCV). Moreover, a case series of four HIV/HCV genotype (HCV-GT)1 patients with rapid virologic response (RVR), who received only 28 weeks of BOC-based triple-therapy (BOCW28), was reported. 290/440 HIV-positive patients with positive HCV serology had at least one visit during the past 2 years, 142/290 had target detectable HCV-RNA with 64% (82/142) carrying HCV-GT1. While 18 HIV/HCV-GT1 displayed contraindications, 45% (64/142) of HIV/HCV were eligible for triple-therapy. Insufficiently controlled HIV-infection despite combined antiretroviral therapy (cART) (HIV-RNA <50 copies/mL: 73% vs. 22%; p<0.001) and liver cirrhosis (31% vs. 8%; p=0.025) were overrepresented among patients with contraindications for triple-therapy. Low treatment uptake rates (39% (25/64)) during the first 2 years of triple-therapy availability suggest that its benefit in HIV/HCV co-infected patients might fall short of expectations. Modification of cART or TPV dose adjustment would have been necessary in 61% and 84% of HIV/HCV-GT1 on cART eligible for triple-therapy using TPV and BOC, respectively, suggesting that drug-drug interactions with cART complicate management in the majority of patients. All four BOCW28 patients achieved a sustained virologic response. Prospective studies are necessary to validate our observations on the shortening of treatment duration in HIV/HCV-GT1 with RVR.

Pioglitazone decreases portosystemic shunting by modulating inflammation and angiogenesis in cirrhotic and non-cirrhotic portal hypertensive rats.

BACKGROUND & AIMS: Development of the portal-hypertensive syndrome is mediated by splanchnic inflammation and neoangiogenesis. Since peroxisome proliferator-activated receptor gamma (PPARγ) agonists like pioglitazone (PIO) regulate inflammatory response and inhibit angiogenesis in endothelial cells, we evaluated PIO as treatment for experimental portal hypertension. METHODS: PIO (10 mg/kg) or vehicle (VEH) was administered from day 21-28 after bile duct ligation (BDL), from day 0-7 after partial portal vein ligation (PPVL) or sham-operation (SO), respectively. After treatment, systemic hemodynamics, splanchnic blood flow (SMABF), portal pressure (PP), and portosystemic shunting (PSS) were assessed. Splanchnic and hepatic tissues were analyzed for angiogenic and inflammatory markers. RESULTS: BDL and PPVL showed significantly increased PP, SMABF, and PSS compared to SO-VEH rats. While PIO treatment did not decrease PP or SMABF, PSS was significantly reduced both in cirrhotic (BDL-VEH: 71% to BDL-PIO: 41%; p<0.001) and non-cirrhotic (PPVL-VEH: 62% to PPVL-PIO: 40%; p=0.041) rats. PIO (10 µM, in vitro) inhibited endothelial cell migration and significantly increased PPARγ activity in vivo. In BDL rats, PIO decreased hepatic mRNA levels of PPARγ (p=0.01) and PlGF (p=0.071), and splanchnic mRNA expression of PPARγ (p=0.017), PDGFß (p=0.053) and TNFα (p=0.075). Accordingly, splanchnic protein expression of PPARγ (p=0.032), VEGFR2 (p=0.035), CD31 (p=0.060) and PDGFß (p=0.066) were lower in BDL-PIO vs. BDL-VEH animals. In PPVL rats, PIO treatment decreased splanchnic gene expression of Ang2 (-12.4 fold), eNOS (-9.3 fold), PDGF (-7.0 fold), PlGF (-11.9 fold), TGFb (-8.3 fold), VEGF-A (-11.3 fold), VEGFR1 (-5.9 fold), IL1b (-14.4 fold), and IL6 (-9.6 fold). CONCLUSIONS: Pioglitazone treatment decreases portosystemic shunting via modulation of splanchnic inflammation and neoangiogenesis. Pioglitazone should be assessed for potential beneficial effects in patients with portosystemic collaterals due to portal hypertension.

Health-related quality of life and severity of fatigue in HIV/HCV co-infected patients before, during, and after antiviral therapy with pegylated interferon plus ribavirin.

UNLABELLED: The aim of this study was to prospectively assess health-related quality of life (HRQL) and severity of fatigue before, during and after antiviral therapy in HIV/HCV co-infected patients. DESIGN: 59 HIV/HCV co-infected patients receiving pegylated interferon plus ribavirin (PEGIFN+RBV) in the HIVCOPEG study were included in this substudy evaluating the secondary endpoints HRQL and severity of fatigue. METHODS: HRQL and severity of fatigue were assessed using SF36 and FSS, respectively. Advanced liver fibrosis was defined as METAVIR F3/F4 or liver stiffness >9.5 kPa. RESULTS: At baseline, advanced liver fibrosis was associated with worse physical health. Mental health was impaired in female patients and in patients with a history of intravenous drug abuse, while a history of depression was associated with higher severity of fatigue. Female gender was associated with a more pronounced relative decrease in mental health during therapy. At follow-up, 24 weeks after the end of therapy, both physical health and fatigue symptoms had improved. Virological response was associated with better physical and mental health, as well as with reduced severity of fatigue. A correlation between anemia grade and the relative impairments in physical health, mental health and fatigue was observed. CONCLUSIONS: Antiviral therapy with PEGIFN+RBV impairs physical and mental health and increases severity of fatigue, while virological response is associated with improvements in physical health and fatigue symptoms. The optimization of anemia management is essential for reducing the burden of impaired HRQL and fatigue in HIV/HCV co-infected patients receiving antiviral therapy with PEGIFN+RBV.

The impact of interleukin 28B rs12979860 single nucleotide polymorphism and liver fibrosis stage on response-guided therapy in HIV/HCV-coinfected patients.

OBJECTIVE: According to the European AIDS Clinical Society (EACS) guidelines for response-guided therapy (RGT) of chronic hepatitis C virus (HCV) infection in HIV-positive patients, HCV-genotype (GT) and rapid virologic response (RVR) exclusively determine the duration of antiviral therapy with pegylated interferon and ribavirin (PEGIFN+RBV). The aim of this study was to investigate the impact of interleukin 28B rs12979860 single nucleotide polymorphism (IL28B) and liver fibrosis stage on RGT in HIV/HCV-coinfected patients. DESIGN: Four hundred and thirty HIV/HCV-coinfected patients treated with PEGIFN+RBV were included in this multinational, retrospective analysis. METHODS: Advanced liver fibrosis was defined as either METAVIR F3/F4 or liver stiffness more than 9.5 kPa. RESULTS: In patients with GT1/4 without RVR (GT1/4-noRVR), higher sustained virologic response (SVR) rates were observed in patients with extended treatment duration (48 weeks: 35% vs. 72 weeks: 60%; P = 0.008). In GT1/4-noRVR patients without advanced liver fibrosis (48 weeks: 45% vs. 72 weeks: 61%; P = 0.176), or with IL28B C/C (48 weeks: 48% vs. 72 weeks: 69%; P = 0.207), SVR rates did not vary significantly throughout the treatment duration subgroups. In contrast, in patients with advanced liver fibrosis (48 weeks: 11% vs. 72 weeks: 45%; P = 0.031), or IL28B non-C/C (48 weeks: 28% vs. 72 weeks: 56%; P = 0.011), extended treatment duration was associated with substantially higher SVR rates. GT2/3 patients with RVR (GT2/3-RVR) with shortened treatment duration (24 weeks) displayed SVR rates ranging from 83 to 100%, regardless of IL28B and liver fibrosis stage. CONCLUSION: Our study confirms the concept of RGT in HIV/HCV coinfection and supports the extension of therapy duration to 72 weeks for patients with GT1/4-noRVR, especially in patients with IL28B non-C/C or advanced liver fibrosis. The results of our study strongly support the shortening of therapy duration to 24 weeks in GT2/3-RVR patients, regardless of IL28B and advanced liver fibrosis.

Low vitamin D levels are associated with impaired virologic response to PEGIFN + RBV therapy in HIV-hepatitis C virus coinfected patients.

BACKGROUND: Low 25-hydroxyvitamin D [25(OH)D] levels are commonly found in HIV-hepatitis C virus (HCV) coinfected patients and are associated with liver fibrosis. No association between 25(OH)D levels and response to pegylated interferon α-2a/2b plus ribavirin (PEGIFN + RBV) has yet been reported for HIV-HCV coinfected patients. DESIGN: Epidemiological characteristics, HIV and HCV infection parameters, liver biopsies, as well as data on virologic response was available in 65 patients who received chronic hepatitis C (CHC) therapy with PEGIFN + RBV within a prospective trial. 25(OH)D levels were retrospectively assessed using stored screening serum samples obtained within 35 days prior to CHC treatment. METHODS: According to their 25(OH)D levels, patients were assigned to the normal (>30 ng/ml; D-NORM), the insufficiency (10-30 ng/ml; D-INSUFF), or the deficiency (<10 ng/ml; D-DEF) group. HCV-GT 1/4, high HCV-RNA load (>6 × 10 IU/ml), advanced liver fibrosis (METAVIR F3/F4), and IL28B rs12979860non-C/C were considered as established risk factors for treatment failure in HIV-HCV coinfected patients. RESULTS: Thirty-seven (57%) and 15 (23%) patients presented with D-INSUFF and D-DEF, respectively, whereas only 13 (20%) patients had normal 25(OH)D levels. Substantial differences in cEVR (D-NORM 92% vs. D-INSUFF 68% vs. D-DEF 47%; P = 0.008) and SVR (D-NORM 85% vs. D-INSUFF 60% vs. D-DEF 40%; P = 0.029) rates were observed between 25(OH)D subgroups. Especially in difficult-to-treat patients with multiple (three to four) established risk factors, low 25(OH)D levels were clearly associated with lower rates of SVR [patients without 25(OH)D deficiency 52% vs. D-DEF 0%; P = 0.012]. CONCLUSION: Low 25(OH)D levels may impair virologic response to PEGIFN + RBV therapy, especially in difficult-to-treat patients. Vitamin D supplementation should be considered and evaluated prospectively in HIV-HCV coinfected patients receiving CHC treatment.

Non-selective betablocker therapy decreases intestinal permeability and serum levels of LBP and IL-6 in patients with cirrhosis.

BACKGROUND & AIMS: We evaluated the gastrointestinal permeability and bacterial translocation in cirrhotic patients with portal hypertension (PHT) prior to and after non-selective betablocker (NSBB) treatment. METHODS: Hepatic venous pressure gradient (HVPG) was measured prior to and under NSBB treatment. Gastroduodenal and intestinal permeability was assessed by the sucrose-lactulose-mannitol (SLM) test. Anti-gliadin and anti-endomysial antibodies were measured. Levels of LPS-binding protein (LBP) and interleukin-6 (IL-6) were quantified by ELISA, and NOD2 and toll-like receptor 2 (TLR2) polymorphisms were genotyped. RESULTS: Fifty cirrhotics were included (72% male, 18% ascites, 60% alcoholic etiology). Abnormal gastroduodenal and intestinal permeability was found in 72% and 59% of patients, respectively. Patients with severe portal hypertension (HVPG ≥20 mm Hg; n=35) had increased markers of gastroduodenal/intestinal permeability (urine sucrose levels p=0.049; sucrose/mannitol ratios p=0.007; intestinal permeability indices p=0.002), and bacterial translocation (LBP p=0.002; IL-6 p=0.025) than patients with HVPG <20 mm Hg. A substantial portion of patients showed elevated levels of anti-gliadin antibodies (IgA: 60%, IgG: 34%) whereas no anti-endomysial antibodies were detected. A significant correlation of portal pressure (i.e., HVPG) with all markers of gastroduodenal/intestinal permeability and with LBP and IL-6 levels was observed. NOD2 and TLR2 risk variants were associated with abnormal intestinal permeability and elevated markers of bacterial translocation. At follow-up HVPG measurements under NSBB, we found an amelioration of gastroduodenal/intestinal permeability and a decrease of bacterial translocation (LBP - 16% p=0.018; IL-6 - 41% p<0.0001) levels, which was not limited to hemodynamic responders. Abnormal SLM test results and higher LBP/IL-6 levels were associated with a higher risk of variceal bleeding during follow-up but not with mortality. CONCLUSIONS: Abnormal gastroduodenal/intestinal permeability, anti-gliadin antibodies, and bacterial translocation are common findings in cirrhotic patients and are correlated with the degree of portal hypertension. NSBB treatment ameliorates gastroduodenal/intestinal permeability and reduces bacterial translocation partially independent of their hemodynamic effects on portal pressure, which may contribute to a reduced risk of variceal bleeding.

A prospective evaluation of pulmonary, systemic and hepatic haemodynamics in HIV-HCV-coinfected patients before and after antiviral therapy with pegylated interferon and ribavirin.

BACKGROUND: Patients coinfected with HIV and HCV are at risk for developing portal hypertension (PHT), hyperdynamic circulation and pulmonary arterial hypertension (PAH). Data on the influence of antiviral therapy with pegylated interferon-α (PEG-IFN-α) and ribavirin (RBV) are limited. METHODS: Haemodynamic parameters, including hepatic venous pressure gradient (HVPG), pulmonary arterial pressure (PAP(mean)), cardiac output (CO) and systemic vascular resistance (SysVR), were prospectively evaluated before and after PEG-IFN-α+RBV therapy in 80 HIV-HCV-coinfected patients. RESULTS: Baseline evaluation showed a mean HVPG of 4.7 mmHg, CO of 6.15 l/min and PAP(mean) of 14.8 mmHg. PHT was present in 26% of patients, hyperdynamic circulation in 5% and PAH in 4%. Patients with advanced fibrosis (METAVIR stage F3/F4; n=32) had significantly higher CO (P=0.008), lower SysVR (P=0.035), higher PAP(mean) (P=0.018) and higher pulmonary vascular resistance (P=0.022) than patients with stage F0-F2 fibrosis (n=48). Both hyperdynamic circulation and PAH were significantly associated with liver stiffness, fibrosis stage and portal pressure; a non-significant trend was found for CD4(+) T-cell counts and HIV RNA levels. No significant changes in PAP(mean), CO and SysVR were observed after PEG-IFN-α+RBV treatment, although a significant decrease in HVPG was noted in patients with HCV eradication (P=0.013). CONCLUSIONS: The overall prevalence of hyperdynamic circulation and PAH in HIV-HCV coinfection is low. Advanced fibrosis, increased liver stiffness, elevated portal pressure and probably CD4(+) T-cell count and HIV viraemia represent risk factors for hyperdynamic circulation and PAH. PHT is present in 26% of HIV-HCV-coinfected patients evaluated for antiviral therapy. Successful HCV eradication significantly decreases HVPG.

IL28B and interferon-gamma inducible protein 10 for prediction of rapid virologic response and sustained virologic response in HIV-HCV-coinfected patients.

BACKGROUND: A polymorphism near the IL28B gene has been shown to be associated with virologic response to antiviral treatment in HCV-infected patients. The predictive value of interferon-gamma inducible protein 10 (IP10) on treatment outcome has been described in HCV patients. Data on combining these predictors in HIV-HCV-coinfected patients are not available. METHODS: Virologic parameters, IL28B single nucleotide polymorphisms (SNP) and pretreatment serum IP10 were determined in HIV-HCV-coinfected patients having completed antiviral therapy with pegylated interferon/ribavirin. RESULTS: A total of 72 HIV-HCV-coinfected patients were included in the study; 68% had HCV genotype (GT)-1/4 and 32% had HCV GT-2/3 infections. Rapid virologic response (63% vs. 28%; P = 0·023) and sustained virologic response (SVR: 81% vs. 51%; P = 0·008) rates were significantly higher in C/C vs. non-C/C patients. Patients with low pretreatment IP10 levels (< 400 pg/mL) achieved significantly higher SVR rates than patients with high (> 400 pg/mL) IP10 levels (78% vs. 13%; P < 0·0001). C/C SNP and low IP10 levels were associated with higher SVR rates in both patients with GT-1/4 and GT-2/3. The C/C patients with low IP10 achieved SVR rates of 97% compared with SVR rates of 9% in non-C/C patients with high IP10. CONCLUSION: The IL28B SNP influences rapid viral response, relapse rates and SVR. The combination of IL28B and IP10 represents a predictive model of SVR in HIV-HCV coinfection.

Considerable under-treatment of chronic HCV infection in HIV patients despite acceptable sustained virological response rates in a real-life setting.

BACKGROUND: According to guidelines, treatment of HCV infection should be considered a priority in HIV-HCV-coinfected patients. METHODS: This multicentre study includes HIV-HCV-coinfected patients diagnosed since 2001 in 14 participating centres in Austria and Germany. Demographic and virological data were recorded. Factors associated with non-initiation of HCV treatment were identified. RESULTS: Among 9,524 HIV patients screened, 1,033 HIV-HCV-coinfected patients were identified (male/female: 760/273; age: 43±9 years; weight: 71±12 kg; CD4(+) T-cell nadir: 255±189 cells/µl; HCV RNA: 3.79×10(6) IU/ml; HIV RNA: 65×10(3) copies/ml). HCV genotype (GT) was predominantly GT-1 (62%). A total of 416 (40%) patients received HCV treatment, whereas 617 (60%) patients remained untreated. The main reasons for deferral of HCV treatment were patient refusal (20%), adherence/compliance (18%), active intravenous drug abuse (14%) and advanced immunodeficiency/AIDS (9%). Patients starting HCV treatment had significantly lower fibrosis stage (F2 versus F4; P<0.0001), higher CD4(+) T-cell count (530 cells/µl versus 430 cells/µl; P<0.0001), lower HIV RNA levels (18×10(3) copies/ml versus 47×10(3) copies/ml; P=0.0008) and higher alanine aminotransferase (ALT; 113 IU/ml versus 75 IU/ml; P<0.0001) than patients without initiation of HCV treatment. Age, HCV GTs, HCV RNA, haemoglobin levels, platelet count and white blood cell count were similar in patients receiving and in patients not receiving antiviral therapy. Multivariate analysis identified ALT levels (P<0.0001) and CD4(+) T-cell count (P<0.0001) as independent predictors of treatment uptake. The overall sustained virological response (SVR) was 41% (155/416), with GT-1 and non-GT1 patients achieving SVR rates of 29% and 48%, respectively. CONCLUSIONS: This large cohort study provides evidence for considerable under-treatment of chronic HCV infection in HIV patients. Despite acceptable treatment success in this real-life setting, HCV remains untreated in the majority of patients and often owing to potentially modifiable reasons.