ABSTRACT
Thirty-eight Swedish patients with chronic hepatitis C were randomly assigned to receive either 3 million units (MU) or 5 MU of human lymphoblastoid interferon-alpha-n1 (Wellferon) three times per week for either 6 or 12 months. The patients were monitored biochemically, histologically and by quantitative polymerase chain reaction for circulating HCV RNA, during therapy and for the following year. Overall, 22 (58%) of the patients lost detectable hepatitis C virus (HCV) viraemia during therapy but eight of these patients relapsed during follow-up, leaving 14 (37%) sustained responders. Patients infected with HCV non-type 1 genotypes were significantly more likely to achieve a sustained response than were those infected with HCV type 1 (63% vs 10.5%, P = 0.001). Sustained virological responses were also associated with lower pretreatment viraemia level, younger age, absence of cirrhosis and the higher interferon dosage regimens but these associations failed to reach statistical significance. In 97% of patients there was concordance between virological and biochemical responses, and a statistically significant (P = 0.005) improvement in the Knodell histological activity index was observed in the virological sustained responders.
Subject(s)
Hepatitis C, Chronic/pathology , Hepatitis C, Chronic/therapy , Interferon-alpha/therapeutic use , Adult , Biopsy , Cohort Studies , Demography , Dose-Response Relationship, Drug , Double-Blind Method , Drug Administration Schedule , Female , Hepacivirus/classification , Hepacivirus/drug effects , Hepacivirus/genetics , Hepatitis C, Chronic/epidemiology , Humans , Injections, Subcutaneous , Interferon-alpha/administration & dosage , Interferon-alpha/adverse effects , Liver/anatomy & histology , Liver/pathology , Liver/virology , Male , Middle Aged , RNA, Viral/blood , RNA, Viral/drug effects , Sweden/epidemiologyABSTRACT
The antiretroviral activity, tolerance and toxicity of two different antiviral drug combinations were assessed and compared in a randomized, crossover pilot study in 16 HIV-1 p24 antigenaemic subjects with asymptomatic HIV infection. Oral zidovudine 250 mg twice daily was combined with either oral acyclovir 800 mg twice daily or lymphoblastoid interferon-alpha 1.5 x 10(6) IU administered subcutaneously three times weekly. The 12-week treatment period was followed by a 4-week washout period and a further 12-week crossover phase. During the entire treatment period a decline in p24 antigen was observed in all patients. No significant differences were found between the two treatment regimens. No patient showed clinical progression of HIV infection. Three patients were withdrawn from the study, one due to serious anaemia and two due to severe clinical adverse events. Long-term efficacy and tolerance data in asymptomatic HIV-infected patients with these regimens would be valuable.
Subject(s)
Acquired Immunodeficiency Syndrome/therapy , Acyclovir/therapeutic use , Interferon-alpha/therapeutic use , Zidovudine/therapeutic use , Acquired Immunodeficiency Syndrome/immunology , Acyclovir/administration & dosage , Acyclovir/adverse effects , Adult , Drug Administration Schedule , Drug Therapy, Combination , Female , HIV Core Protein p24/blood , Humans , Injections, Subcutaneous , Interferon-alpha/administration & dosage , Male , Middle Aged , Pilot Projects , Zidovudine/administration & dosage , Zidovudine/adverse effectsABSTRACT
Reduction of HIV p24 antigenaemia by zidovudine was investigated in 34 HIV antibody-positive, asymptomatic patients in a randomised, double-blind, placebo-controlled trial. Zidovudine was shown to lower p24 antigen levels as effectively when administered twice daily as when administered four times daily. Serum levels of p24 antigen varied little over 18 weeks in patients taking placebo.
Subject(s)
HIV Core Protein p24/analysis , HIV Infections/drug therapy , Zidovudine/therapeutic use , Adult , Analysis of Variance , CD4-Positive T-Lymphocytes/pathology , Double-Blind Method , Drug Administration Schedule , Female , HIV Infections/blood , HIV Infections/immunology , Hemoglobins/analysis , Humans , Leukocyte Count , Male , Placebos , Zidovudine/administration & dosage , Zidovudine/adverse effectsABSTRACT
The serotype-specific capsular polysaccharide from two strains of Pasteurella haemolytica serotype A1 organisms was purified and characterized by chemical analysis and NMR spectroscopy. The polymer has the structure----3)-O-(2-acetamido-2-deoxy-4-O-acetyl-beta-D-mannopyranos yluronic acid)-(1----4)-O-(2-acetamido-2-deoxy-beta-D-mannopyranose)-(1----. The polysaccharide was immunogenic (able to evoke production of antibodies) for sheep but not for rabbits. Immuno electron-microscopy studies using the Protein A-gold technique showed the polysaccharide to be peripherally located on the bacterial surface. Reduction, oxidation and de-O-acetylation of the polymer did not appear to alter its immunological precipitability with specific antiserum, but all three treatments destroyed its ability to adhere to sheep erythrocytes at neutral pH. De-N-acetylation of the polymer destroyed both immunological precipitability and erythrocyte adherence.
