Search

Objective: The frequency and significance of, and liver biopsy findings associated with, a persistently normal alanine aminotransferase (ALT) level in HIV/hepatitis C virus (HCV)-coinfected patients are poorly characterized. We analysed factors associated with persistently normal ALT levels, defined as at least three consecutive normal ALT values over a 6-month period, in a group of 381 HIV/HCV-coinfected patients., Methods: Patients were categorized into two groups according to ALT values: group 1, patients with persistently normal ALT levels; and group 2, patients with elevated ALT values. Possible interactions with host factors, HIV and HCV viral factors, antiretroviral treatment and histological features were examined., Results: Thirty-six patients (9.4%) had persistently normal ALT levels. None of the 36 patients had cirrhosis. Seven patients (19.4%) had a METAVIR fibrosis score of F3. In multivariate analysis, a lower mean METAVIR inflammation score [odds ratio (OR) 0.50, 95% confidence interval (CI) 0.28-0.89; P=0.017], the absence of steatosis (OR 0.43, 95% CI 0.20-0.90; P=0.026) and HCV genotype 4 infection (OR 2.81, 95% CI 1.15-6.68; P=0.023) were associated with persistently normal ALT levels., Conclusion: The slower progression of chronic hepatitis in patients with persistently normal ALT levels could be related, in part, to a lower frequency of steatosis.

Background/aims: To compare non-invasive biological liver fibrosis scores, as alternatives to liver biopsy, in HIV/HCV co-infected patients., Methods: Two hundred and seventy-two HIV/HCV patients, nai ve for HCV treatment, underwent liver biopsy [197 (72%) men, 39.9 years, fibrosis stage (Metavir) F1 (25%), F2 (40%), F3 (25%), F4 (10%), median CD4 486/mm(3) and median HIV viral load 3.5log. Fibrotest (FT), Hepascore (HS), Fibrometer (FM), SHASTA, APRI, Forns index, and Fib-4 were tested in order to differentiate patients with mild to moderate fibrosis (F2) and those with advanced fibrosis (F3). The AUROC and the rate of well-classified patients were compared to liver biopsy., Results: FT, HS, and FM were able to stage liver fibrosis in all patients with AUROCs of 0.78, 0.84 and 0.89 for the diagnosis of F2, respectively. The correlation coefficient indexes were 0.37, 0.46 and 0.48, respectively. The rates of well-classified patients were 62%, 68% and 71%, respectively. Fib-4, APRI and the Forn's index were only able to stage 37-61% of patients and showed lower accuracies. Using a combination of FT, HS and FM did not significantly increase the performance of each test., Conclusions: In HIV/HCV co-infected patients, Fibrometer, Hepascore and Fibrotest outperformed other non-invasive liver fibrosis biomarkers for the prediction of significant liver fibrosis.

Weight loss is reported by more than 20% of hepatitis C virus (HCV)-monoinfected patients treated with the peg-interferon (peg-IFN) and ribavirin combination. The aim of this study was to determine the incidence and risk factors of severe weight loss (> or =10%) in human immunodeficiency virus (HIV) / HCV-coinfected patients participating in a randomized, controlled 48-week trial comparing peg-IFN alpha 2b plus ribavirin with IFN alpha-2b plus ribavirin. Univariate and multivariate analyses were used to identify links with antiretroviral treatments, anti-HCV therapy and clinical and laboratory findings. One hundred eleven (28.9%) of 383 patients who received at least one dose of anti-HCV treatment subsequently had severe weight loss. Among patients who took at least 80% of the planned total dose, severe weight loss occurred in 74 patients (32.7%). In multivariate analysis, age >40 years [hazard ratio (HR), 1.59; 95% CI 1.09 to 2.31; P = 0.016], body mass index (BMI) >22 (HR, 1.72; 95% CI, 1.16 to 2.55; P = 0.0069), peg-IFN alpha-2b (HR, 1.82; 95% CI, 1.24 to 2.69; P = 0.0022) and female sex (HR, 1.60; 95% CI, 1.05 to 2.43; P = 0.027) were associated with severe weight loss. In contrast, patients taking non-nucleoside reverse transcriptase inhibitors (NNRTI)-containing antiretroviral regimens were less likely to lose weight (HR, 0.62; 95% CI, 0.39 to 0.96; P = 0.034). Lipodystrophy tended to occur more frequently in patients who had severe weight loss than in the other patients (26.1%vs 17.6%; P = 0.0682) and patients whose weight loss >5% persisted 24 weeks after the completion of anti-HCV therapy (n = 58 / 111) were more likely to be receiving stavudine-based antiretroviral therapy, suggesting that mitochondrial toxicity plays some role in weight loss. These findings show that severe weight loss is a frequent side effect of anti-HCV therapy in HIV / HCV-coinfected patients. The underlying mechanisms remain to be identified.

Background/aims: To analyze the barriers to HCV treatment in HIV-HCV co-infected patients and their evolution between 2004 and 2006., Methods: Three hundred and eighty HIV-HCV co-infected patients were prospectively included in surveys from November 22 to 29, 2004 (2004 survey), and 416 from April 3 to 10, 2006 (2006 survey)., Results: Patients in 2006 compared to those in 2004 had negative HCV RNA more often (24% vs. 12%). The rate of liver biopsy was similar (56% vs. 54%) while 24% had had a non-invasive liver damage assessment. The rate of previous treatment for HCV infection was higher (48% vs. 26%). The main reasons for HCV non-treatment have changed: HCV treatment deemed questionable (44% vs. 53%), lack of liver biopsy (18% vs. 33%), physicians' conviction of poor patient compliance (20% vs. 30%). In both surveys, HCV treated patients were more often of European origin, had better control of HIV infection, and had a liver damage assessment more often., Conclusions: The care of HIV-HCV co-infected patients has changed significantly in "real life". These results underline the importance of continuing efforts to educate physicians and patients in order to increase the access of co-infected patients to HCV treatment.

To analyse the barriers for anti-hepatitis C virus (anti-HCV) treatment in human immunodeficiency virus (HIV)-HCV coinfected patients, we surveyed 71 physicians specializing in infectious disease (39%), internal medicine (27%), HIV/AIDS information and care (17%), haematology (10%) and hepatology (6%). A standard data collection form was used to identify patients observed in 7 days in November 2004. Three hundred and eighty patients with the following characteristics were included: male gender 71%; mean age 41.5 years; HIV diagnosed 12 years ago; routes of transmission via injection drug use (78%); undetectable HIV viral load (235/373, 63%) or <10 000 copies/mL (86/373, 23%). HCV RNA was positive in 325 of 369 (88%) patients; HCV genotype was 1 or 4 in 65% and liver biopsy had been carried out in 56%. There were several explanations for the nontreatment of HCV in 205 of the 380 (54%) patients, with 2.4 reasons per patient: anti-HCV treatment was deemed questionable (n = 109) because of minor hepatic lesions, alcohol consumption, or active drug use; no liver biopsy had been performed (n = 68); treatment was contraindicated (n = 62), mainly for psychiatric reasons; there was physician conviction of poor patient compliance (n = 62) and patient refusal (n = 33). Patients having received anti-HCV treatment (n = 91) compared with those who had never received any (n = 205) were more commonly of European origin, had better control of their HIV infection, were followed by a hepatologist more often, had a liver biopsy more often and had more commonly a high HCV viral load (P < 0.001). In 'real life' in France in 2004, more than half of the HIV-HCV coinfected patients have never received anti-HCV treatment. The main reasons are a treatment that may be deemed questionable (minimal hepatic lesions, alcohol, active drug use), a lack of available liver biopsy, a psychiatric contraindication and physician conviction of poor patient compliance.

Trak-C (Ortho-Clinical Diagnostics) is an enzyme-linked immunosorbent assay-based method capable of quantifying hepatitis C virus (HCV) core antigen (CA) in serum and could be an alternative to molecular detection and quantification of HCV RNA. We have evaluated the Trak-C assay in comparison with an HCV RNA quantitative assay (Versant HCV v3.0; Bayer Diagnostics) in the follow-up of 348 treated, human immunodeficiency virus (HIV)/HCV-coinfected patients included in the ANRS HC02 RIBAVIC trial. ANRS HC02 RIBAVIC is a therapeutic, multicenter, randomized protocol comparing the efficacy of alpha interferon 2b (IFN-alpha2b) (3 million units three times a week)-ribavirin (800 mg/day) to that of pegylated IFN-alpha2b (1.5 mug/kg of body weight/week)-ribavirin (800 mg/day) during 48 weeks of treatment of HIV/HCV-coinfected patients naïve to HCV treatment. Patients were assessed for virological analysis at day 0 and weeks 4, 12, 24, 48, and 72. Correlation of HCV RNA and HCV CA at the initiation of treatment was excellent (r = 0.92). HCV RNA and CA kinetics were similar during follow-up of HCV treatment from day 0 to week 72 whatever the group of response and genotype. The positive and negative predictive values of response to the treatment at week 4 were 59 and 94%, respectively, for HCV RNA load reduction of >2 log and 54 and 94%, respectively, for HCV CA below the threshold value (4.18 log(10) pg/ml . 10(4)). Trak-C, a new assay able to quantify CA in HIV/HCV-coinfected patients, correlates well with quantitative HCV RNA assays and is cheaper and easier to perform than molecular technology. HCV CA could be a valuable alternative test for therapeutic follow-up of coinfected patients treated with IFN plus ribavirin in developing countries.

Spontaneous hepatic decompensation was observed in 7 of 383 patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) who were receiving treatment with interferon and ribavirin. Multivariate analysis identified the following risk factors: didanosine use (odds ratio [OR], 8.8; 95% confidence interval [CI], 1.2-102.3; P < .02), cirrhosis, (OR, 8.8; 95% CI, 1.2-104.2; P<.02), and elevated total bilirubin level (OR, 7.9; 95% CI, 1.08-93.3; P<.03). Didanosine should thus not be given to patients with cirrhosis, particularly when treatments for HCV and HIV infections have to be administered concomitantly.

Objective: To evaluate the incidence, clinical features, and risk factors for symptomatic mitochondrial toxicity in HIV/hepatitis C virus (HCV)-coinfected patients receiving anti-HCV therapy., Methods: All cases of symptomatic mitochondrial toxicity reported in 416 patients participating in an open, randomized trial of peg-interferon alpha-2b plus ribavirin vs. interferon alpha-2b plus ribavirin for 48 weeks were reviewed. Associations with antiretroviral treatments and with clinical and laboratory findings were sought by univariate and multivariate analysis., Results: Eleven of the 383 patients who received at least 1 dose of anti-HCV treatment developed symptomatic mitochondrial toxicity (symptomatic hyperlactatemia and pancreatitis in 6 and 5 patients, respectively). All cases occurred in patients being treated for HIV infection, and the incidence of symptomatic mitochondrial toxicity was 47.5 per 1000 patient-years. In multivariate analysis, symptomatic mitochondrial toxicity was significantly associated with didanosine-containing antiretroviral regimens (odds ratio 46; 95% CI, 7.4 to infinity; P < 0.001), but not with stavudine or with nucleoside reverse transcriptase inhibitor regimens not containing didanosine. The incidence of symptomatic mitochondrial toxicity was 200.2 per 1000 patient-years in patients receiving didanosine. Demographic characteristics were not associated with symptomatic mitochondrial toxicity., Conclusions: Coadministration of ribavirin with didanosine should be avoided. If unavoidable, patients should be monitored closely for mitochondrial toxicity. Didanosine should be suspended if clinical signs or symptoms of mitochondrial toxicity occur.

Treating Hepatitis C among HIV patients under antiretroviral drug therapy requires a high degree of vigilance and continuous monitoring because of frequent problems with intolerance and/or drug interactions. Recent studies, including three therapeutic trials, on Ribavic, APRICOT, and ACTG A5671, have given some insights on following these patients up. The adverse effects are relatively similar in HCV-HIV-co-infected patients and patients infected by HCV only. Their frequency is, on the other hand, higher among HCV-HIV-Co-infected patients. The adverse-effects are consistent, in a non-exhaustive way, with pseudo influenza-like symptoms, fever, myalgia, cephalgia, with psychiatric disorders (irritability, depression, etc.); endocrine disorders (thyroid dysfunction, diabetes...); and with hematological anomalies especially anemia and leucopenia. But the percentage of lymphocyte T CD4 is not modified, therefore there is no risk of opportunistic infection. Pharmacokinetic interactions between antiretroviral drugs and treatment for HCV infection including ribavirin plus interferon alpha (IFN-alpha) or pegylated IFN are described. They are almost exclusively due to the combination of ribavirin and of nucleoside analogue reverse transcriptase inhibitors. One of the principal consequences is the emergence of mitochondrial toxicity defined by the occurrence of hyperlactatemia, or acute pancreatitis). Thus, some combinations should be avoided such as ddI+ribavirin and ddI+d4T+ribavirin. The d4T+ribavirin combination must also be used with caution.

Several studies have suggested that the progression of hepatitis C virus (HCV) infection is more severe in patients infected by the human immunodeficiency virus (HIV). Two national retrospective multicenter cohort surveys were performed in France that included 17,487 HIV-infected patients during 1995 and 26,497 during 1997. The following data was evaluated: total number of deaths; number of deaths linked to AIDS, cirrhosis, or hepatocellular carcinoma (HCC); and number of deaths related to other (non-HCV--linked) causes. In 1995, the causes of death were as follows: AIDS, 1307 (7.47%); cirrhosis or HCC, 21 (0.12%); and other (non-HCV--linked) causes, 99 (0.56%). In 1997, the causes of deaths were as follows: AIDS, 459 (1.73%); cirrhosis or HCC 36 (0.13%); and other (non-HCV--linked) causes, 48 (0.18%). Comparative results between the 1995 and 1997 surveys showed a dramatic decrease in AIDS-related mortality rates (7.47% vs. 1.73%; P<.001) but not in HCV-related mortality rates (0.06% vs. 0.07%; P=.79). In France, despite the high prevalence of HCV infection in HIV-positive patients, the mortality rate in 1995 and 1997 caused by HCV-related cirrhosis or HCC was low.

Purpose: Hepatitis C (HCV) has a high prevalence (10-30%) among human immunodeficiency virus (HIV)-infected patients. However, little information is available regarding the impact of hepatitis C on survival. The objective of our study was to determine the incidence of hepatitis C-related deaths in HIV-HCV co-infected patients., Methods: The study was a retrospective (1-year), multicenter cohort survey conducted in 63 departments of either internal medicine or infectious diseases in France. It included 26,497 HIV-infected patients, of whom 4,465 (16.8%) presented coinfection due to the hepatitis C virus. The following parameters were studied for the year 1997: total number of deaths, number of deaths related to either AIDS, cirrhosis, hepatocellular carcinoma, or other causes., Results: Among the 26,497 patients, 543 deaths (incidence: 2%) were observed in 1997; 543 deaths were due to AIDS (incidence: 1.7%), 36 to cirrhosis and/or hepatocellular carcinoma (incidence: 0.13%), and 48 (incidence: 0.18%) to another cause. In the subgroup including 4,465 HIV-HCV-coinfected patients, 29 deaths (incidence: 0.64%) were due to either HCV-related cirrhosis or hepatocellular carcinoma. These results were compared with those of a previous similar survey conducted in 1995, before the era of highly active antiretroviral therapy. The only significant difference is the dramatic regression of deaths due to AIDS., Conclusion: The impact of hepatitis C virus on the mortality among HIV-infected patients whose follow-up took place in departments of either internal medicine or infectious diseases in France was very low in 1997. The expected increase in the life span in these patients could modify these results in the future, due to recent improvements in the HIV infection treatment.