Human immunodeficiency virus (HIV) infection is associated with progressive loss of circulating CD4+ lymphocytes. Treatment with highly active antiretroviral therapy (HAART) has led to increases in CD4+ T lymphocytes of naive (CD45RA+62L+) and memory (CD45R0+RA-) phenotypes. Thymic computerized tomography scans were obtained on 30 individuals with HIV disease to investigate the role of the thymus in cellular restoration after 48 weeks of HAART. Individuals with abundant thymic tissue had higher naive CD4+ T lymphocyte counts at weeks 2-24 after therapy than individuals with minimal thymic tissue. Individuals with abundant thymic tissue had significantly larger increases in naive CD4+ cells during the first 4 weeks of therapy. These individuals were also more likely to experience viral rebound despite comparable initial declines in plasma HIV-1 RNA. These findings suggest that there is a complex relationship among the thymus, viral replication, and lymphocyte restoration after application of HAART in HIV disease.

Asymptomatic individuals seropositive for human immunodeficiency virus (HIV) progress in a heterogeneous fashion toward AIDS. To facilitate monitoring of disease progression and response to therapy, a rapid, new flow cytometric assay (FCA) lymphocyte p24-FCA, has been devised to quantify peripheral blood lymphocytes expressing cell-associated HIV-1 p24 antigen. Results from 55 asymptomatic, HIV-1-seropositive, serum p24 antigen-negative individuals ranged from undetectable (less than 0.1%) to 13.6% p24+ lymphocytes (mean, 2.0%). Mean values for three other groups studied were 0.1% for seronegative, viral culture-negative laboratory workers (n = 24); 4.2% for untreated patients with AIDS (n = 16); and 0.3% for AIDS patients receiving zidovudine (n = 11). Lymphocyte p24-FCA values were inversely related to the number of days to positive viral cultures and to levels of CD4+ lymphocytes. The ratio of p24+ lymphocytes to CD4+ lymphocytes may reflect the fraction of infected CD4+ lymphocytes. Lymphocyte p24-FCA determination may provide a method for monitoring response to antiretroviral therapy regardless of serum p24 antigen status.

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The effects of ketoconazole alone and in combination with acyclovir and adenine arabinoside upon the replication of herpes simplex virus types 1 and 2 (HSV-1 and -2) were investigated by using a yield reduction assay. Ketoconazole demonstrated antiviral activity against HSV-1 and -2 and synergistic antiviral activity when it was combined with acyclovir. Combinations of ketoconazole with adenine arabinoside resulted in either interference or indifference. The effects of ketoconazole upon the protein synthesis of HSV-2-infected cells were also determined in an effort to define the mechanism of action for the antiviral activity of ketoconazole. There was no reduction of' HSV proteins when compared with acyclovir. These findings suggest that further investigations of the use of ketoconazole for the treatment of HSV infections are warranted.Recently, several reports have described a novel approach to antiviral chemotherapy with the antifungal' agent amphotericin B. Amphotericin B, a polyene antibiotic, exerts its antifungal effect by binding to sterol components in the fungal cell membrane, which results in increased permeability of the membrane (11). By using the water-soluble the combined effects of amphotericin B and acyclovir upon the replication of pseudorabies virus. Low doses of amphotericin B in combination with acyclovir produced a synergistic reduction in viral replication as shown with a plaque reduction assay. The exact mechanism for this synergistic effect was not elucidated (9).In view of this promising work, we investigated the possibility of antiviral activity for a different antifungal agent, ketoconazole. Ketoconazole is an imidazole compound which' exerts its antifungal activity through inhibition of lanosterol demethylation. This blocks the synthesis of ergosterol, the major sterol component of the fungal cell membrane (2). In mammalian cells, ketoconazole also inhibits lanosterol demethylation, with a subsequent decrease in the biosynthesis of cholesterol, the major sterol component of mammalian cell membranes. In addition, ketoconazole interferes with cellular fatty acid and phospholipid biosynthesis (2). In this study, we examined the effects of ketoconazole alone and in combination with acyclovir and adenine arabinoside upon herpes simplex virus types 1 and 2 (HSV-1 and -2) replication with a yield reduction assay. 107 PFU/ml were grown in monolayers of Vero cells and stored at -70°C.Cells. Vero and human lung (HL) cells (derived from an HL carcinoma) were used in all assays. Vero cells were grown in RPMI 1640 supplemented with 10% inactivated fetal bovine serum, 1% glutamine, 100 U of penicillin per'ml, and 50 jig of streptomycin per ml; and HL cells were grown in Hanks balanced salt solution, basal medium Eagle improved, supplemented with 10% inactivated fetal bovine serum, 1% glutamine, 100 U of penicillin per ml, and 50 ,ug of streptomycin per ml. Maintenance medium for both cell lines was supplemented with 1% inactivated fetal bovine serum in place of 10% inactivated fetal bovine serum.Dr...

We have evaluated a new enzyme immunoassay (EIA) to measure IgG antibodies (Abs) to HIV in patients with AIDS, AIDS-related complex (ARC), AIDS contacts (AC), and low risk controls. Twenty-nine (94%) of 31 AIDS, 27 (96%) of 26 ARC, 12 (54%) of 22 AC, and 1 (2%) of 60 control patients were anti-HIV Ab positive by this assay. Positive results were confirmed by Western blot analysis. The EIA for anti-HIV evaluated in this study is sensitive and specific in identifying individuals who have been infected by this retrovirus.