Search

Aims: The current treatment of choice is a combination of pegylated interferon-alfa (PegIFN-alfa) plus ribavirin. Prediction of IFN efficacy before treatment has been mainly based on viral characteristics such as viral load and genotype. We therefore analyzed data from a large multicentric German surveillance study in order to identify additional host- related predictors of nonresponse. Methods: Between 9/2003 and 8/2008, 279 active sites treated a total of 4039 patients with weight-based PegIFN-alfa2b and ribavirin. As this is an ongoing surveillance trial, we have performed an interim analysis of formerly untreated noncirrhotic patients with HCV-genotype 1 and nonresponse defined as HCV-RNA-positivity at end of treatment (EOT) as well as at the end of follow-up (EOF) 6 months after end of treatment. Results: 455 treated patients with genotype 1 failed to achieve HCV-RNA-negativity at EOT and EOF, while 614 patients experienced sustained virological response after 6 months of follow-up (SVR). Baseline data and rapid virologic response (RVR) in both groups are shown in the table. Because data were not available in all patients the number of patients fluctuates throughout the subgroups analyzed. No dose reductions of either PegIFN-alfa2b or ribavirin were performed in 437 (71.2%) of patients with SVR and 324 (71.2%) in the nonresponder-group. Reductions of ribavirin have been made in 69 (11.2%) of SVR-patients and 31 (6.8%) of patients with nonresponse, respectively. Only 7/209 (3.3%) nonresponding patients, who were tested for HCV-RNA at week 4, experienced an RVR, while 21.4% of all SVR-patients exhibited an RVR. Conclusions: Regarding baseline predictive values, there is a significant difference in age as well as baseline viral load while other factors such as body weight and BMI seem not to predict nonresponse in noncirrhotic patients. In contrast, RVR may predict low nonresponse rates, as break through after week 4 are rare events. Data were analyzed using standard summary statistics and two-sided 95% confidence intervals.

As the natural history of HIV infection has changed following the introduction of highly active antiretroviral therapy (HAART), morbidity and mortality in the afflicted patients could be significantly reduced. The decreasing risk of suffering from opportunistic infections and tumors, however, is at the cost of antiretroviral drug-related toxicities. Today, mortality by liver disease is the major cause of death in HIV-infected patients from industrial countries. In the US and Europe about 30% of HIV-positive individuals are also infected with hepatitis C virus (HCV), and approximately 50-90% of persons who acquired HIV from injecting drugs are coinfected with HCV. In these dually infected individuals the presence of each viral infection impacts the natural history of the other one, and worsening of associated liver disease and complications within this population are increasing. The management of chronic hepatitis C (cHC) in HCV-HIV coinfection has become a major challenge, since possible interactions with antiretroviral therapies, increased risk of special side effects and compromises in adherence in patients already taking several drugs have to be taken into account. On the other hand, treatment strategies to fight HCV have been essentially ameliorated during the past 2 years by using pegylated interferon-alpha2b (Peg-IFN-alpha2b) combined with ribavirin, and there is hope that the successful therapeutic outcome in HCV-monoinfected individuals may beat least partly translated into benefits for the difficult-to-treat population of HCV-HIV dually infected persons. During the 15th International AIDS Conference in July 2002 in Barcelona, a satellite symposium, as well as a session in the main program and a number of poster presentations focussed on HCV-HIV coinfection and addressed the urgent problems and therapeutic challenges in managing cHC in the situation of underlying HIV disease.

In the course of HIV infection, the role of interferon-α (IFN-α) seems to be rather paradoxical: “It is possible to view alpha-IFN as either a therapeutical agent or as a major contributor to the pathology associated with AIDS.” (S. Krown, 1992).

The reasons why immunodeficiency leads to malignant disorders are multifactorial. The overall incidence of malignancies in persons infected with the human deficiency virus (HIV) is estimated to be 40%. Other infecting agents, especially herpesvirus species, play a pivotal role in HIV-associated non-Hodgkin's lymphoma (NHL) and Kaposi's sarcoma (KS). Mucosaassociated lymphatic tissue (MALT) lymphoma in the stomach may be a result of a chronic gastritis caused by Helicobacter pylori, a gram-negative bacterium. The Epstein-Barr virus (EBV) genome can be found in a high percentage of lymphoma cells of HIV-NHL (nearly 100% in the primary lymphoma of the CNS and about 50% in all other lymphoma entities). In body-cavity based NHL, characterized by the absence of EBV and c-myc oncogen, sequences of a herpesvirus were identified which corresponds to the gamma-herpes viremia found in KS. The Kaposi's sarcoma-associated herpesvirus (KSHV) was usually present in primary-effusion lymphoma (PEL). HIV-infection, which causes multiple dysfunctions within the immune system, triggers the cytokine dysregulation. An abnormal endogenous interferon (IFN)-alpha production is observed in HIV-infected patients with KS, especially in the later natural course of the disease. A monitoring of the IFN-system by MxA, a protein specifically induced by IFN's of type I, may be a necessary stratum of identifying patients who show superior effects and the greatest clinical benefit from treatment with IFN-alpha.

with poor response to HCV therapy, or may normalize with HCV eradication. We retrospectively interrogated the IDEAL database to examine the role of MS in HCV therapy. Methods: 3070 treatment-naive, HCV genotype-1 infected adults received peginterferon (PEG) alfa-2b 1.5 or 1mg/kg/wk plus ribavirin (RBV) 800–1400mg/d or PEG alfa-2a 180mg/wk plus RBV 1000– 1200mg/d. Metabolic syndrome was defined by the IDF/AHA criteria requiring 3/5 of: 1. fasting glucose≥5.6mmol/L or use of diabetes medications, 2. elevated blood pressure (≥130/85) or use of antihypertensivemedications, 3. triglycerides >150mg/dL, 4. HDL-C 102 cm (males) or 88 cm (females). Results: 30.3% of patients had MS at baseline, with lower sustained virologic response (SVR) in those with MS (34.9% vs 41.6%, p < 0.001). This difference was greater in women (34.7% vs 43.2%, p = 0.006) than men (35.0% vs 40.5%, p = 0.024). MS was a negative predictor for response (OR=1.3) in nearly all subgroups, with a higher odds ratio in those with advanced fibrosis (OR=1.7). SVR was lower with each additional component of the MS definition present, with the largest decrease from 2 criterion (SVR = 40.0%) to 3 criterion (SVR = 35.5%), which is consistent with the MS definition. Multivariate regression including MS and each of its components shows that elevated glucose has the best negative predictive value (OR=1.72) but ‘high’ HDL is a negative predictor of SVR (OR=1.50); waist circumference and MS are no longer significant predictors of SVR. Patients with both high glucose and HDL (18.1%; 557/3070) had a low probability of SVR (OR=1.97). Removing central obesity from the MS criteria (not measured in FU), 56% of those with baseline MS no longer met diagnostic criteria six months after completion of therapy (48% if SVR, 60% if no SVR) due to normalization of one or more of the other factors. Conclusions: MS is a negative predictor of response to PEG/RBV therapy. Surprisingly, ‘high’ HDL was also a negative predictor of SVR. Independent of SVR, MS normalized in the majority of patients post-therapy.

About 30% of HIV-positive individuals are concomitantly infected with HCV within the United States and Europe. Approximately 50 to 90 % of persons who acquired HIV from injecting drugs are co-infected with HCV. In these dually infected individuals the presence of each viral infection may impact the natural course of the other one, and worsening of associated liver disease and complications within this population are frequent. The management of chronic hepatitis C (cHC) in HCV-HIV-co-infection has become a major challenge, as possible interactions with antiretroviral therapy (ART), increased risk of special side effects, as well as compromises in adherence of patients, who already take several drugs, have to be taken into account. Treatment strategies to fight HCV-infection have been essentially ameliorated during the past three years in using pegylated interferon alpha (PegIFN alpha) combined with ribavirin (Rbv). There is hope that the beneficial therapeutic outcome in HCV-mono-infected individuals may be at least partly translated into successful treatment of dually infected patients too. However, the stepwise amelioration of therapeutic options and strategies does actually not yet result in equal anti-HCV response rates for co-infected compared to HCV-mono-infected persons. The 1st International Workshop on HIV and Hepatitis Co-infection 2004, was initiated to face the severe clinical problems which arise from viral hepatitis and HIV dual infection. The organising committee was headed by J. K. Rockstroh, University of Bonn, Germany, as chair and M. Sulkowski, John Hopkins University, USA, as co-chair of the meeting, in which more than 300 researchers and physicians from various European and US locations participated. This report summarizes some results on epidemiology, pathogenesis, viral interactions, and treatment of chronic hepatitis C in HIV-infected individuals.

HIV-pathogenesis involves both pathogenic effects on some HIV infected cells and indirect effects on uninfected bystander cells. It has been self-evident for almost 20 years that reducing the amount of virus is beneficial to infected patients, as reduction in HIV-RNA viral load blocks direct as well as indirect pathogenic effects of HIV-1. However, eradication has not been achieved. As during suppressive HAART (highly active antiretroviral therapy) a great variety of cells can become HIV-reservoirs, they feature as numerous potential targets for new therapeutic approaches as for instance immune-based therapy.

As in totally 1% of the worldwide population is afflicted by hepatitis C virus with most of the 200 Mio carriers not diagnosed or treated, the clinical management of chronic hepatitis C remains an urgent demand for global health. The 12th European Congress of Clinical Microbiology and Infectious Diseases (12th ECCMID) held in Milan, Italy, from 21 to 24 April 2002, focussed on viral hepatitis in a keynote lecture as well as a session on evidence based treatment of chronic infection and various poster presentations.

Though AIDS-related morbidity and mortality are generally decreasing as a result of highly active antiretroviral therapy (HAART) and prevention of opportunistic infections, dual infection with HCV and HIV leads to an acceleration in the natural course of chronic hepatitis C (cHC) and worsening of associated liver disease and complications. Mortality from co-morbid HCV infection within this population is increasing and has become a major challenge in the management of HIV-related complications. As treatment strategies to fight cHC have been essentially ameliorated within the recent two years in using pegylated interferon-alfa2b (Peg-IFN-alfa2b) combined with ribavirin, t here is hope that the successful therapeutic outcomes in HCV-mono-infected individuals may be partly translated into benefits for the difficult-to-treat patients with HCV-HIV co-infection. A number of issues arise when beginning HCV treatment during HAART, as for instance possible interactions with antiretroviral therapies, increased risk of special side effects, and a compromise in adherence due to the addition of new medication in patients already taking several drugs. On the other hand there is also the chance that Peg-IFN-alfa2b fights HIV as well as HCV. First data of pre-load therapy with Peg-IFN-alfa2b in treatment-na ve HIV-positive individuals before the initiation of HAART have also been presented during the 8th European Conference on Clinical Aspects and Treatment of HIV Infection (8th ECCATH), October 2001 in Athens.

Viral hepatitis features with an incidence of 500 Mio infected individuals worldwide. Chronification of the infection as seen in hepatitis C, B, and D may lead to liver cirrhosis and its associated complications in later stages of the disease. Especially the chronification of acute hepatitis C is observed in a majority of cases (50-80%). Chronic Hepatitis C (cHC) should be treated in generally when elevated serum concentrations of liver enzymes are found or symptoms of disease occur. Treatment goals are viral elimination, improve in histology, prevention of HCC, and a better quality of life for the patients. As HCV and HIV share the same transmission routes, a relatively high rate of HCV-HIV co-infection is observed. Co-infection is characterized by a more progressive natural course of HCV-infection, leading to an increased mortality due to liver failure in the afflicted patients. The development of treatment options for anti-HCV-specific therapy in dually infected patients is urgently needed. The European Conference on Infectious Diseases and Tropical Medicine, EuCID 2001, which took place in May 3-6, 2001, in Leipzig covered aspects of viral hepatitis and its treatment in several sessions and gave latest results on treatment with interferon-alfa, lamivudine, and adefovir in hepatitis B as well as interferon-alfa, pegylated interferon-alfa, and ribavirin in hepatitis C and HCV-HIV co-infection respectively.