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Objectives: To compare the frequency of grade 3 or 4 transaminase elevations (TEs) in HIV/hepatitis C virus (HCV) co-infected patients who started a three-antiretroviral drug regimen including efavirenz or a ritonavir-boosted protease inhibitor (PI/r) and the influence of pre-existing significant hepatic fibrosis or cirrhosis., Patients and Methods: All pre-treated or treatment-naive HIV/HCV co-infected patients who started an antiretroviral regimen including two nucleos(t)ide reverse transcriptase inhibitors along with efavirenz or a PI/r in seven Spanish centres from January 2007 to December 2009 were included in this prospective study., Results: Of 262 patients included in this study, 76 (29%) individuals began antiretroviral therapy (ART) including efavirenz and 186 (71%) a PI/r-based combination. The median (interquartile) follow-up was 14.0 (6.2-23.7) months. A total of 20 (7.6%) patients presented grade 3-4 TEs. Four (1.5%) subjects discontinued ART due to this adverse event. Grade 3-4 TEs were observed in 5 (6.6%) subjects receiving efavirenz and 15 (8.1%) treated with PI/r (P = 0.681). Three (6.5%) patients in the efavirenz group with significant fibrosis developed grade 3-4 TEs versus 2 (8.7%) without pre-existing significant fibrosis (P = 0.743). In the PI/r group, the corresponding figures were 10 (8.8%) and 5 (9.3%), respectively (P = 0.931)., Conclusions: The frequency of grade 3-4 TEs associated with efavirenz-based ART combinations under clinical practice conditions is low and similar to that found in patients receiving PI/r currently used in HIV/HCV co-infected patients. The baseline fibrosis stage does not have an impact on the development of TEs caused by these antiretroviral drugs in this population.

Background: Liver stiffness (LS) measured by transient elastometry is associated with portal pressure in hepatitis C virus (HCV)-monoinfected patients and could predict the presence of esophageal varices in these subjects. The aim of this study was to assess the ability of LS to predict esophageal varices requiring preventive therapy for bleeding in HIV/HCV-coinfected patients., Methods: One hundred two HIV/HCV-coinfected patients with liver cirrhosis (LS >or= 14 kPa) underwent an upper gastrointestinal endoscopy (UGE) examination. The diagnostic performance of LS for esophageal varices requiring therapy (>or=F2 or F1 with red signs or Child-Pugh-Turcotte class C) was assessed by receiver operating receptor characteristic curves., Results: Nineteen patients (19%) harbored varices requiring therapy. LS in patients with and without varices needing treatment was 48 (33-71) kPa and 32 (18-48) kPa (P = 0.004). The area under the receptor operating characteristic curve (95% confidence interval) of LS for the occurrence of varices that should be treated was 0.71 (0.60 to 0.82). There was no cutoff level of LS with good positive predictive value for the presence of varices requiring therapy, but LS of 21 kPa had a negative predictive value of 100%. Twenty-six percent of patients with LS measurement and UGE showed LS <21 KPa., Conclusions: LS is higher in HIV/HCV-coinfected patients with cirrhosis who show esophageal varices requiring therapy than in those who do not. A cutoff value of LS of 21 kPa could be useful to identify patients with very low probability of varices at risk for bleeding. UGE for screening could be spared in these patients until LS increases above 21 kPa.

Background/aims: To evaluate the possible influence of baseline insulin resistance in sustained virological response., Methods: One hundred and fifty-five consecutive individuals from a multicentric cohort of HIV/HCV co-infected patients who underwent therapy with pegylated interferon plus ribavirin were included. The main outcome variable was sustained virological response, defined as undetectable plasma HCV RNA at week 24 after the end of the therapy. Insulin resistance was determined using the HOMA method., Results: Sustained virological response was achieved in 55 (36%) patients. Forty-two (38%) patients with a HOMA lower than 4 developed sustained virological response vs 13 (29%) of those with a HOMA above 4 (p=0.27). Analyses restricted to patients harbouring genotype 1 or 4 showed similar rates of sustained virological response among patients with a HOMA below and above 4 [19 (27%) vs 7 (24%); p=0.8]. In the multivariate analysis, genotype 3 [AOR 9.26; 95% CI 3.03-28.30; p<0.0001], a baseline HCV viral load below 600.000IU/mL [AOR 2.97; 95% CI 1.03-8.57; p=0.04] and baseline LDL cholesterol above 100mg/dL [AOR 6.62; 95% CI 1.97-22.19; p=0.002] were independently associated with sustained virological response., Conclusions: Insulin resistance is not a relevant predictor of sustained virological response to pegylated interferon plus ribavirin in HIV/HCV co-infected patients.

Objectives: To investigate whether concomitant antiretroviral therapy (ART) is a predictor of sustained virological response (SVR) in human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients treated with pegylated interferon plus ribavirin., Methods: Three hundred and ten HIV/HCV-coinfected patients on pegylated interferon plus ribavirin treatment, 258 of them with concurrent ART, were included in this retrospective multicentre study. The predictors of SVR were evaluated., Results: SVR was shown by 114 (37%) subjects. HCV genotype 2 or 3, plasma HCV-RNA load lower than 600 000 IU/mL, an exposure to the therapy against HCV infection > or =80% of the planned dose and baseline CD4 cell counts higher than or equal to 300/mm(3) were predictors of SVR. Likewise, patients without ART and those receiving a combination including tenofovir or stavudine plus lamivudine plus a protease inhibitor (PI) or a non-nucleoside reverse transcriptase inhibitor (NNRTI) showed a higher SVR rate than the subjects who were on other ART strategies at baseline [44%, 44% and 29%, respectively; adjusted odd ratio (95% CI) for no ART = 1.96 (1.07-4.76), P = 0.025, and for ART including tenofovir or stavudine plus lamivudine plus a PI or a NNRTI = 2.08 (1.16-3.70), P = 0.014]., Conclusions: The ART strategy on starting therapy with pegylated interferon plus ribavirin is a predictor of SVR in HIV/HCV-coinfected patients. Subjects without ART and those receiving combinations of a PI or a NNRTI with a nucleos(t)ide backbone of tenofovir or stavudine plus lamivudine respond better than those who receive other regimens.

Background: Transient elastometry (TE) is accurate for detecting significant liver fibrosis and cirrhosis in hepatitis C virus (HCV)-monoinfected patients. However, this procedure has been insufficiently validated in patients with human immunodeficiency virus (HIV) and HCV coinfection. The purpose of this study was to validate reported cutoff values of TE that discriminate significant liver fibrosis and cirrhosis in HIV-HCV-coinfected subjects., Methods: Liver stiffness measurements were obtained for 169 HIV-HCV-coinfected adult patients who had undergone a liver biopsy or who had received a nonhistologic diagnosis of cirrhosis within 12 months before or after a liver stiffness measurement. Patients had received no prior therapy for HCV infection., Results: TE measurements ranged from 3.6 kPa to 75 kPa. The area under the receiver operating characteristic curve was 0.87 (95% confidence interval, 0.84-0.93) for significant liver fibrosis and 0.95 (95% confidence interval, 0.92-0.99) for cirrhosis. To diagnose significant liver fibrosis, a cutoff value of 7.2 kPa was associated with a positive predictive value of 88% and a negative predictive value of 75%. Thirty-four patients (20%) were misclassified when this cutoff value was used. Thirteen (24%) of 54 patients with liver stiffness values <7.2 kPa had significant liver fibrosis detected by liver biopsy. To diagnose cirrhosis, a cutoff value of 14.6 kPa was associated with a positive predictive value of 86% and a negative predictive value of 94%. Thus, 13 patients (10%) had disease that was misclassified using this cutoff value., Conclusions: We found that the diagnostic accuracy of TE was high for detecting cirrhosis and good for diagnosis of significant liver fibrosis. However, the performance of TE was low for discriminating mild fibrosis from significant liver fibrosis, which might limit the applicability of this technique in clinical practice.

Objective: To find the survival and the predictors of death of HIV-infected patients with hepatitis C virus (HCV)-related end-stage liver disease (ESLD)., Design and Methods: A prospective cohort study set in the infectious diseases units of four tertiary care public hospitals in Andalucía, Spain. From a multicentric cohort of 2664 HIV/HCV-co-infected patients, all consecutive patients with HCV-related cirrhosis who presented with the first hepatic decompensation from January 1997 to June 2004 were followed-up and 153 patients were included. The survival and the demographic, HIV-related and liver-related factors associated with death were evaluated., Results: Ninety-five (62%) patients died during the follow-up. In 79 (85%) individuals, the cause of death was liver related. The median survival time was 13 months. Independent predictors of survival were Child score [hazard ratio (HR), 1.2; 95% confidence interval (CI), 1.08-1.37; P = 0.001], CD4+ cell count at decompensation lower than 100 cells/microl (HR, 2.48; 95% CI, 1.52-4.06; P < 0.001) and hepatic encephalopathy as the first hepatic decompensation (HR, 2.45; 95% CI, 1.41-4.27; P = 0.001). HAART was prescribed to 101 (66%) patients. The cumulative probability of survival in patients under HAART was 60% at 1 year and 40% at 3 years, versus 38 and 18%, respectively, in patients not treated with HAART (P < 0.0001). The HR (95% CI) of death in patients on HAART was 0.5 (0.3-0.9), (P = 0.03). CONCLUSIONS The survival of HIV/HCV-co-infected patients with ESLD is extremely poor. Immunosuppression and markers of severe liver disease predict liver-related mortality in these patients. HAART seems to be associated with a reduced liver-related mortality.

The impact of human immunodeficiency virus (HIV) coinfection on the survival of patients with hepatitis C virus (HCV)-related end-stage liver disease (ESLD) is unknown. Because HIV infection is no longer considered an absolute contraindication for liver transplantation in some countries, it has become a priority to address this topic. The objective of this study was to compare the survival of HIV-infected and HIV-uninfected patients with decompensated cirrhosis due to HCV. In a retrospective cohort study, the survival of 1,037 HCV monoinfected and 180 HCV/HIV-coinfected patients with cirrhosis after the first hepatic decompensation was analyzed. Of the group, 386 (37%) HCV-monoinfected and 100 (56%) HCV/HIV-coinfected subjects died during the follow-up. The median survival time of HIV-infected and HIV-uninfected patients was 16 and 48 months, respectively (P < .001). The relative risk (95% CI) of death for HIV-infected patients was 2.26 (1.51-3.38). Other independent predictors of survival were age older than 63 years (2.25 [1.53-3.31]); Child-Turcotte-Pugh class B versus class A (1.95 [1.41-2.68]) and class C versus class A (2.78 [1.66-4.70]); hepatitis D virus infection (1.56 [1.12-4.77]); model for end-stage liver disease score, (1.05 [1.01-1-11]); more than one simultaneous decompensation (1.23 [1.12-3.33]); and the type of the first hepatic decompensation, with a poorer prognosis associated with encephalopathy compared with portal hypertensive gastrointestinal bleeding (2.03 [1.26-3.10]). In conclusion, HIV coinfection reduces considerably the survival of patients with HCV-related ESLD independently of other markers of poor prognosis. This fact must be taken into account to establish the adequate timing of liver transplantation in HIV-coinfected subjects.