Badley, Andrew D

ABSTRACT Inhibition of human immunodeficiency virus type 1 reverse transcriptase (RT) by both nucleoside and nonnucleoside RT inhibitors profoundly inhibits virus replication. Nucleoside RT inhibitors are known to be toxic, but there is little information regarding the toxicities of nonnucleoside RT inhibitors (NNRTI). We demonstrate that efavirenz (an NNRTI) induces caspase- and mitochondrion-dependent apoptosis of Jurkat T cells and human peripheral blood mononuclear cells. The clinical relevance of these observations is not yet clear.

▪ Abstract The HACEK group of fastidious gram-negative organisms is a recognized but unusual cause of infective endocarditis, responsible for approximately 3% of cases. We report our experience with 45 cases of endocarditis caused by HACEK organisms. In Olmsted County, Minnesota, the incidence of HACEK endocarditis was 0.14 per 100,000 person-years. In patients with native valves, 33 cases occurred, and in patients with prosthetic valves, 12 cases occurred. The most common presenting symptoms were fever, splenomegaly, new or changing murmur, and microvascular phenomena. Symptoms were present in the majority of patients anywhere from two weeks to six months prior to diagnosis. Blood cultures became positive in a mean of 3.375 days, and therapy with a beta-lactam alone or as part of a combination was given for anywhere between three and six weeks. Within the first month of diagnosis, surgery was performed for 13 regurgitant valves in 11 patients (24%). Echocardiography was an insensitive predictor of subsequent major arterial embolization (odds ratio, 1.33; 95% confidence interval, 0.31–5.67). The overall survival in our cohort of patients was 87%. These results confirm previous reports that HACEK endocarditis portends a favorable prognosis.

Apoptosis of bystander uninfected CD4+ T lymphocytes by neighboring HIV-infected cells is observed in cell culture and in lymphoid tissue of HIV-infected individuals. This study addresses whether antigen-presenting cells such as human macrophages mediate apoptosis of CD4+ T cells from HIV-infected individuals. Uninfected human macrophages, and to a larger degree, HIV-infected macrophages mediate apoptosis of T cells from HIV-infected, but not from uninfected control individuals. This macrophage-dependent killing targets CD4+, but not CD8+ T lymphocytes from HIV-infected individuals, and direct contact between macrophages and lymphocytes is required. Additional analyses indicated that the apoptosis-inducing ligands, FasL and tumor necrosis factor (TNF), mediate this macrophage-induced apoptosis of CD4+ T cells. These results support a role for macrophage-associated FasL and TNF in the selective depletion of CD4+ T cells in HIV-infected individuals.