Histoplasmoma: isolated central nervous system infection with Histoplasma capsulatum in a patient with AIDS. Case report and brief review of the literature.

Histoplasma capsulatum is endemic to the Ohio and Mississippi River valleys. Exposure to H. capsulatum is very common in this region and usually follows a benign clinical course. However, immunocompromised hosts, like those with HIV/AIDS, are more susceptible to symptomatic infection, and have a greater chance of developing disseminated disease. We report an unusual case of a patient with AIDS presenting with a single ring-enhancing brain lesion and a focal neurological deficit. Workup was unrevealing, and brain biopsy was felt to represent too much risk as the lesion was located at the right tegmentum. The lesion enlarged over a period of months, and he underwent radiation therapy after the lesion caused obstructive hydrocephalus. He expired soon after completion of radiation therapy. At autopsy, the mass lesion was noted to contain organisms constant with H. capsulatum, pathologically consistent with a histoplasmoma.

Intermittent episodes of detectable HIV viremia in patients receiving nonnucleoside reverse-transcriptase inhibitor-based or protease inhibitor-based highly active antiretroviral therapy regimens are equivalent in incidence and prognosis.

BACKGROUND: Intermittent episodes of detectable human immunodeficiency virus (HIV) viremia (hereafter referred to as "blips") are generally not predictive of subsequent virologic failure. Limited data are available for patients treated with nonnucleoside reverse-transcriptase inhibitor (NNRTI)-based regimens. METHODS: A retrospective cohort study evaluated patients receiving highly active antiretroviral therapy who were followed for > or =12 months, achieved an HIV RNA load of <50 copies/mL, and underwent evaluation every 2-3 months. A blip was defined as 1 HIV RNA load measurement of 50-1000 copies/mL that was preceded and followed by another HIV RNA load measurement of <50 copies/mL. The frequency and predictors of blips and virologic failure were studied. RESULTS: There were 244 patients in the NNRTI group and 136 patients in the protease inhibitor (PI) group. Baseline characteristics between the 2 groups were similar. A total of 34% of patients in the NNRTI group and 33% in the PI group experienced viral blips (P=.855), with corresponding incidences of 19.2 and 19.7 blips, respectively, per 100 person-years. Median time to blips was 50.0 months after initiation of therapy in the NNRTI group (95% confidence interval [CI], 44.8-55.3 months) and 43.6 months in the PI group (95% CI, 33.7-53.6 months; P=.632, by the log-rank test). By Cox proportional hazards model analysis, only a history of antiretroviral therapy use (hazard ratio [HR], 2.01; P<.001) and a CD4 cell count of <200 cells/ mu L (HR, 1.70; P=.021) increased the risk for having a blip. During a median follow-up period of 23.5 months, 7.8% of patients in the NNRTI group and 8.1% in the PI group experienced virologic failure (P=.917). Cox proportional hazards model analysis showed that only a baseline CD4 cell count of <200 cells/ mu L predicted virologic failure (HR, 2.74; P=.032). CONCLUSIONS: There is no difference in the frequency or prognostic significance of viral blips between patients receiving NNRTI-based therapy and patients receiving PI-based therapy. Our results suggest that viral blips occur at a similar rate among patients receiving NNRTI-based regimens and patients receiving PI-based regimens and that they are not predictive of virologic failure.

Undetectable plasma HIV RNA load predicts success after hepatitis B vaccination in HIV-infected persons.

Human immunodeficiency virus (HIV)-infected patients respond poorly to hepatitis B vaccination. Records of 194 HIV-infected patients were reviewed for factors associated with successful hepatitis B vaccination. Thirty-four patients (17.5%) developed a protective antibody response. In a logistic regression model, only a plasma HIV RNA level of <400 copies/mL at the time of vaccination was associated with a protective antibody response (P=.003).

Requirement for kasB in Mycobacterium mycolic acid biosynthesis, cell wall impermeability and intracellular survival: implications for therapy.

Mycobacterium tuberculosis infects one-third of the world's population and causes two million deaths annually. The unusually low permeability of its cell wall contributes to the ability of M. tuberculosis to grow within host macrophages, a property required for pathogenesis of infection. Mycobacterium marinum is an established model for discovering genes involved in mycobacterial infection. Mycobacterium marinum mutants with transposon insertions in the beta-ketoacyl-acyl carrier protein synthase B gene (kasB) grew poorly in macrophages, although growth in vitro was unaffected. Detailed analyses by thin-layer chromatography, nuclear magnetic resonance (NMR), matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, infrared spectroscopy, and chemical degradations showed that the kasB mutants synthesize mycolic acids that are 2-4 carbons shorter than wild type; the defect was localized to the proximal portion of the meromycolate chain. In addition, these mutants showed a significant (approximately 30%) reduction in the abundance of keto-mycolates, with a slight compensatory increase of both alpha- and methoxy-mycolates. Despite these small changes in mycolate length and composition, the kasB mutants exhibited strikingly altered cell wall permeability, leading to a marked increase in susceptibility to lipophilic antibiotics and the host antimicrobial molecules defensin and lysozyme. The abnormalities of the kasB mutants were fully complemented by expressing M. tuberculosis kasB, but not by the closely related gene kasA. These studies identify kasB as a novel target for therapeutic intervention in mycobacterial diseases.