Search

We compared the activity of delavirdine (DLV) plus zidovudine (AZT) (n = 300) with that of AZT (n = 297) against human immunodeficiency virus type 1 in a randomized, double-blind, placebo-controlled trial. DLV exerted a transient antiviral effect, and mutations for resistance to DLV were found in more than 90% of subjects at week 12. The K103N mutation, which confers nonnucleoside reverse transcriptase inhibitor cross-resistance, was found in 85% of the patients.

Effective new therapies are required to combat the increasing incidence of mycobacterial infections. Rifabutin has been investigated in studies conducted in various countries around the world, and in the treatment of tuberculosis rifabutin in combination regimen has been shown to be as effective as rifampicin. Rifabutin is active in approximately 30% of patients with tuberculosis resistant to standard therapies, including rifampicin and/or isoniazid. Placebo-controlled studies of rifabutin in the treatment of Mycobacterium avium-intracellulare complex (MAC) infection in AIDS patients have provided evidence for the inclusion of rifabutin in multidrug regimens. Rifabutin as a single agent is the only drug approved for the prophylaxis of MAC infection. Clinical experience indicates that rifabutin is well tolerated and that it does not reduce the tolerability of combination regimens.

C57BL/6 mice, which differ genetically from other strains by their resistance to herpes simplex virus type 1 (HSV-1) infection, were inoculated intraperitoneally with different doses of tumour necrosis factor alpha (TNF-alpha). Mice pretreated with 100 ng, or even 10 ng, of TNF-alpha showed prolonged survival compared to control mice that were infected with 10(7) p.f.u. of HSV-1. Significant protection was observed in mice injected 4 or 8 h prior to or after HSV-1 inoculation, respectively. Protection was also observed when mice which differed at their H-2 locus were treated with TNF-alpha after infection with HSV-1. Interferon could not be detected in the sera of mice at different time points after infection with HSV-1 or injection of TNF-alpha and there was no enhanced interferon titre in mice treated with both TNF-alpha and HSV-I, suggesting some interferon-independent protection. However, mice treated with TNF-alpha showed a marked activation of natural killer (NK) cells compared to untreated control mice or mice that were treated with HSV-1 alone. To test whether enhanced NK cell activity is responsible for TNF-alpha-induced protection, mice were injected with the NK cell-specific antibody anti-asialo Gm-1. In this experimental protocol the survival rate was almost unaffected, indicating that the observed protection was not due to activation of NK cells and that TNF-alpha is involved in the regulation of antiviral mechanisms other than the activation of interferons. Although additional production of interferon induced by TNF-alpha cannot be excluded, an antiviral effect of TNF-alpha on the course of HSV-1 infection may be postulated from our data.