ISSN:0300-5526    

DOI:10.1159/000150561

出版商:S. Karger AG    

年代:1997

数据来源: Karger

ISSN:0300-5526    

DOI:10.1159/000150562

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

The acyclic nucleoside phosphonates [HPMPC (cidofovir), PMEA (adefovir) and PMPA] have proved to be effective in vitro (cell culture systems) and in vivo (animal models, clinical studies) against a wide variety of DNA virus and retrovirus infections: i.e., HPMPC against herpesvirus (herpes simplex virus type 1 and 2, varicella-zoster virus, cytomegalovirus, Epstein-Barr virus, human herpesvirus types 6, 7, and 18), polyoma-, papilloma-, adeno-, and poxvirus (vaccinia virus, molluscum contagiosum virus) infections; PMEA against herpesvirus, hepadnavirus (human hepatitis B virus) and retrovirus (human immunodeficiency virus type 1 and 2, simian immunodeficiency virus, and feline immunodeficiency virus) infections; and PMPA against both hepadna- and retrovirus infections.

ISSN:0300-5526    

DOI:10.1159/000150563

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Potent new antiretroviral drugs combined with updated treatment strategies have now achieved efficient inhibition of HIV replication in most patients. The major targets for antiretroviral therapy are the reverse transcriptase and the protease of HIV. Up to date, 11 antiretroviral drugs have been licensed in the US. New nucleoside reverse transcriptase inhibitors (NRTI), i.e. abacavir, and adefovir dipivoxil proved to be effective in clinical trials. The antiretroviral activity and impact on clinical outcome of nonnucleoside reverse transcriptase inhibitors (NNRTI) are mostly short lived. Compared to NRTIs, protease inhibitors (Pis) have the highest antiretroviral activity. New Pis that conserve activity against mutant HIV strains or derivatives that have a simpler biosynthesis are being developed. A major drawback of highly active antiretroviral therapy is the selection of resistant mutants under suboptimal dosage, in advanced stages of disease or after pre-treatment with mono- or double-combination regimens. Monitoring of antiretroviral therapy is achieved by measurement of viral load using nucleic acid amplification techniques. The goal of antiretroviral therapy should be to reduce viral load below the detection limit of current assays in order to delay the emergence of resistant mutants and to maximally reduce disease progression. Recommendations for antiretroviral therapy and monitoring are evolving constantly due to the rapid progress in the development of active compounds and new insights into HIV pathogenesis. Resistance determination of HIV patient isolates seems to play a progressively increasing role in monitoring of antiretroviral treatment since treatment-naive patients may already harbour drug-resistant virus. Due to cross-resistance between different compounds, the choice of the treatment regimen should be guided by resistance patterns of HIV in order to warrant maximal and long-lasting efficiency.

ISSN:0300-5526    

DOI:10.1159/000150564

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

After several nucleoside analogues have been tested against chronic hepatitis B virus (HBV) infection with minimal success, lamivudine seems to be a highly effective new therapeutic option. This review focusses on nucleoside metabolism and on the molecular action of lamivudine as well as on results of clinical studies for several indications. We report on results of trials on the use of lamivudine for chronic HBV infection, chronic HBV under immunosuppression and prophylaxis or treatment of HBV reinfection before or after orthotopic liver transplantation. Aspects of combination therapy of different nucleoside analogues as well as on combination of lamivudine with interferon are also highlighted. Although lamivudine seems to be highly effective in most patients at the start of therapy, development of resistance by mutations in the viral polymerase is a significant clinical problem. The mode of resistance development is compared with the situation in HIV infection. Possible cross-resistance with other nucleoside analogues and the perspectives of lamivudine therapy are also considered.

ISSN:0300-5526    

DOI:10.1159/000150565

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Famciclovir (FCV, the oral form of penciclovir, PCV) is a potent antiviral agent of hepatitis B virus (HBV) and is currently in phase III clinical trials. In this review, we examine the outcome of FCV treatment in preventing recurrent HBV in patients post transplantation. Resistance to FCV has now been documented in this setting, in which reduced sensitivity to FCV was associated with mutations upstream from the conserved ‘YMDD’ motif in the HBV polymerase gene. These mutations are in a region which has been designated as the B domain in RNA-dependent polymerases. To understand these mutations we have developed a model of the catalytic regions of the HBV polymerase and located mutations selected during antiviral treatment on this mo

ISSN:0300-5526    

DOI:10.1159/000150566

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Antiviral treatment of herpesvirus infections is rapidly changing since the advent of new drugs with improved oral availability. The efficacy of valaciclovir, the prodrug of aciclovir, and famciclovir, the prodrug of penciclovir, in the treatment of herpes genitalis and acute herpes zoster has been well documented in large clinical trials. Both drugs are effective on zoster-associated pain. Brivudin and sorivudine which are the most active compounds against varicella-zoster virus (VZV) in cell culture have also been successful in the treatment of herpes zoster. Aciclovir is still the standard therapy of severe herpes simplex virus (HSV) and varicella virus infections. In patients treated with aciclovir, the mortality of herpes encephalitis has been reduced to about 25%. The development of resistance against aciclovir and the other nucleoside analogues has not been a problem to date in the treatment of immunocompetent individuals. However, in immunocompromised patients, aciclovir-resistant HSV strains often emerge. In such cases, intravenous foscarnet is the current treatment of choice.

ISSN:0300-5526    

DOI:10.1159/000150567

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

This review summarizes current strategies for the treatment of human cytomegalovirus (CMV) infection/diseases in high-risk patients such as transplant recipients and AIDS patients. Since the major drugs ganciclovir (Cytovene), foscarnet (Foscavir) and cidofovir (Vistide) are frequently associated with severe side effects and the formation of viral resistance, it should be endeavored to develop better strategies in anti-CMV treatment. Moreover, blocking of the viral replication does not always resolve the manifestations which are often linked with CMV-associated immunopathomechanisms. Thus, the efficacy of the available drugs is also discussed in the light of their ability to modulate inflammatory components of the cell-mediated immune system.

ISSN:0300-5526    

DOI:10.1159/000150568

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Papillomavirus infections are very common and cause various benign and malignant lesions, most notably condyloma acuminatum, anogenital cancer, laryngeal papilloma and skin warts. Unfortunately, effective therapy is currently not available. Therapeutic options are limited, expensive and often ineffective. They comprise cytodestructive and cytotoxic substances, surgical methods, laser and cryotherapy. Immunotherapy seems to be one of the more promising options. Interferons combined with ablative methods such as CO2 laser can prevent recurrence of disease. Cytokine enhancement is an old concept that has shown effectiveness with imidazoquinolinamine derivatives (imiquimod). Imiquimod was released recently for therapy of genital warts. Currently, HPV vaccines are being developed to protect against infection with HPV and to treat existing warts and other HPV-associated lesions. Some processes in the HPV infection cycle have been determined as possible targets for the development of specific antiviral agents. Cidofovir is a primordial antiviral substance active against HPV. Unfortunately, there is a potential risk for side effects.

ISSN:0300-5526    

DOI:10.1159/000150569

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

The hepatitis C virus (HCV) was identified as the major causative agent of posttransfusion and community-acquired non-A, non-B hepatitis throughout the world. It is an enveloped virus with a plus-strand RNA genome encoding a polyprotein of about 3,010 amino acids. This polyprotein is cleaved co- and posttranslationally into mature viral proteins by host cell signal peptidases and 2 viral enzymes designated the NS2-3 proteinase and the NS3/4A proteinase complex. It is assumed that virus replication takes place in a membrane-associated complex containing at least 2 viral enzymatic activities: the NS3 nucleoside triphosphatase (NTPase)&slash;helicase and the NS5B RNA-dependent RNA polymerase (RdRp). Based on their important role for the viral life cycle and the wealth of information available for related cellular and viral proteins, the NS3/4A serine-type proteinase complex, the NS3 NTPase/helicase and the NS5B RdRp are the most attractive targets for development of HCV-specific antiviral therapies. This review will summarize our current knowledge about structure and function of these proteins and describe approaches pursued to identify effective antiviral compounds.

ISSN:0300-5526    

DOI:10.1159/000150570

出版商:S. Karger AG    

年代:1997

数据来源: Karger