Viral infections are among the in t...

Viral infections are among the in the greatest degree formidable conditions in the primary care setting, causing a wide range of illnesses that are difficult to treat. Developing antiviral medicines has been difficult because greatest in number drugs that kill viruses also damage the host's confined apartments However, since the first antiviral put drugs into amantadine (Symmetrel), was released in 1966 encouraging progres has been made in this area. Part I of this two-part article focuses forward antiviral agents used to treat hepatitis, cytomegalovirus (CMV) and herpes infections in nonimmunosuppressed patients. Important issues in the management of viral infections in patients with human immunodeficiency virus (HIV) infection and in solid-organ or bone-marrow transplant patients are not reviewed.

Hepatitis Viruses

HEPATITIS B

Chronic hepatitis B virus (HBV) infection affects 5 percent of the worldwide population and may lead to cirrhosis and hepatocellular carcinoma. HBV infection is considered chronic when surface antigen persists for more than six month Three criteria for treating chronic HBV include alanine aminotransferase (ALT) plain greater than two times normal and positive experiments for HBV DNA and hepatitis B e antigen (HbeAg) (Table 1) All three criteria should be ready before patients are considered for anti-HBV therapy. The treatment of choice in these patients is interferon alfa-2b (Intron A) (1) [Evidence plain B, cohort study] or lamivudine (Epivir-HBV). (2) More lately adefovir dipivoxil (Hepsera) was approved for use in chronic HBV infection. (3)

Interferon Alfa-2b. rejoinder to interferon alfa-2b (defined as los of HBeAg and HBV DNA) befalls in 30 to 40 percent of patients. Unfortunately, interferon is associated with significant side validitys including flu-like symptoms (e.g., headaches, heats myalgias, fatigue), thrombocytopenia, leukopenia, depression, weight los rash, cough hypo- or hyperthyroidism, tinnitus, auto-antibody formation, and retinopathy. Lamivudine. Lamivudine is a nucleoside turn topsy-turvy transcriptase inhibitor that is used to treat HIV and HBV infections. answer rates to lamivudine are similar to those obtained with interferon alfa-2b, and lamivudine is typically greatly better tolerated. (2) [Evidence on a level A, randomized controlled trial (RCT)] However, unsalable article resistance is a major difficulty associated with lamivudine. Resistance make knowns after one year of treatment in 15 to 30 percent of patients. Unlike interferon alfa-2b, lamivudine is approved for use in patients with decompensated cirrhosis resulting from HBV infection.

Adefovir Dipivoxil. Adefovir dipivoxil is a nucleotide subvert transcriptase inhibitor with a mechanism of action similar to that of lamivudine. In early studies, resistance to adefovir dipivoxil appears to be strange Adefovir dipivoxil also can be used effectively in patients who are resistant to lamivudine. (34) It is likely that coming treatment protocols for HBV infection will use multiple combination regimens, although in the same state [i]or[/i] condition regimens are currently experimental.

HEPATITIS C

Hepatitis C virus (HCV) is the principally frequent cause of end-stage liver disease in the United States and the leading indication for liver transplant. (5) Therefore, as with chronic HBV it is important that physicians consider treatment options in any HCV-infected patient.

Therapy for chronic HCV infection is indicated in patients with a detectable HCV RNA viral load and a persistently elevated ALT horizontal Findings of cirrhosis, fibrosis, or calm moderate inflammation on liver biopsy support the choice of therapeutic intervention, nevertheless biopsy is not mandatory before initiating therapy. (5)

Pegylated Interferon Alfa and Ribavirin. The standard treatment regimen for chronic HCV infection is outlined in Table 1 Pegylated interferon alfa-2a (Pegasys) and pegylated interferon alfa-2b (PEG-Intron) are modified forms of interferon alfa with frequently longer half-lives, which allow these physics to be taken once a week. In addition, they are significantly more effective against HCV either alone or in combination with ribavirin (Rebetol), compared with unmodified interferon alfa, and they have side general intent profiles similar to that of unmodified interferon alfa. (67) [Reference 6 and 7--Evidence even A, RCT]

The HCV viral load should be assessed after 24 weeks of therapy. fresh studies suggest that patients infected with HCV genotype 2 or 3 should receive a total course of 24 weeks of therapy, while patients with genotypes 1 or 4 have higher sustained virologic reply rates if they are treated for 48 weeks. In patients with genotype 1a or 1b infection, the detection of viremia at 24 weeks predicts viral persistence despite therapy. Thus, it is praiseed that patients with viremia at 24 weeks discontinue therapy. Because viremia at 12 weeks now appears to predict persistent HCV infection, more [i]or[/i] less experts recommend discontinuing therapy at 12 weeks if HCV viremia is discovered In patients with genotype 1a or 1b (and probably genotype 4 as well) and an undetectable HCV viral load at 24 weeks, continuation of therapy for the abounding 48-week course is indicated.