Survival of AIDS patients with primary central nervous system lymphoma is dramatically improved by HAART-induced immune recovery.

OBJECTIVE: To evaluate the impact of immune recovery induced by highly active antiretroviral therapy (HAART) on the survival of AIDS patients with primary central nervous system lymphoma (PCNSL). METHODS: In a multicentric retrospective analysis, 29 HIV-infected patients with histologically confirmed PCNSL were identified. To evaluate median survival, Kaplan-Meier statistics were used. To explore the effects of different variables on survival, a Weibull accelerated failure time regression analysis was performed. RESULTS: Median age at manifestation of PCNSL was 39.1 years and median CD4 cell count was 11 x 10(6) cells/l. Seventy per cent of the patients had had a prior AIDS-defining illness. Cranial radiation (CR) was given to 12 out of 29 patients. Six patients were treated with HAART. Survival time of these patients and of the patients treated with CR alone differed significantly from those receiving neither CR nor HAART (median Kaplan-Meier survival estimate: 1093, 132, and 33 days, respectively). In the multivariate regression model, HAART and CR were identified as the only variables independently associated with prolonged survival. HAART versus no HAART and CR versus no CR increased the time to event by a factor of 6.1 (95% confidence interval, 2.4-16.0; P = 0.0002) and 3.1 (95% confidence interval, 1.5-6.3; P = 0.002), respectively. Four out of six patients on HAART showed a marked immune recovery and survived for more than 1.5 years, with two patients still alive. CONCLUSION: Data from this cohort indicate that immune recovery induced by HAART leads to dramatic improvement in survival of patients with AIDS-associated PCNSL. These findings may have important implications for future treatment strategies.

[Severe colitis due to Histoplasma capsulatum in an AIDS patient]. / Schwere Kolitis durch Histoplasma capsulatum bei einer Patientin mit Aids.

The case of a thirty-two-year-old female HIV-positive patient from Ghana admitted with a septic illness, diarrhoea, anaemia, and severe weight loss is presented. During an extensive diagnostic work-up Mycobacterium tuberculosis infection and typhoid fever were detected. Specific treatment led to marked improvement in the patient's condition. However, five weeks later high fever and diarrhoea recurred. Histological examination of biopsies from coloscopy and blood cultures revealed Histoplasma capsulatum. The patient recovered completely following antifungal therapy with amphotericin B and itraconazole. The case presented emphasises the need for medical staff dealing with immunocompromised patients from endemic areas to be aware of symptoms, diagnostic features, and therapeutic measures of this rare fungal infection.

Quantification of JC virus DNA in the cerebrospinal fluid of patients with human immunodeficiency virus-associated progressive multifocal leukoencephalopathy--a longitudinal study.

In progressive multifocal leukoencephalopathy (PML) the JC virus (JCV) load in the cerebrospinal fluid (CSF) is discussed as a parameter for disease progression. To investigate the evolution of viral shedding into the CSF, the JCV DNA concentration was quantified by competitive polymerase chain reaction (PCR) in multiple CSF samples from prior to and during an unsuccessful intrathecal salvage therapy in 2 human immunodeficiency virus-infected patients with biopsy-proven PML. With continuous clinical progression the virus load varied considerably intra- and interindividually, ranging from nondetectable to 1.2x108 genome equivalents/10 microliter CSF. Whereas an overall increase during progressive disease was confirmed, the virus burden was either constant or fluctuated irregularly during the intermediate stage of disease. This shows a variability of viral shedding during active disease that must be taken into account when the JCV load is measured by quantitative PCR for both the diagnosis of PML and monitoring under investigational treatment.

HIV infection of the central nervous system is characterized by rapid turnover of viral RNA in cerebrospinal fluid.

To assess the kinetics of viral replication and decay in cerebrospinal fluid (CSF), we studied the short-term effects of highly active antiretroviral therapy (HAART) on CSF HIV-1 RNA concentrations. In 15 HIV-positive patients, HIV RNA concentrations were measured in paired CSF and plasma/serum samples. Samples were obtained prior to and 5 to 24 days after initiation or change of HAART. The short-term effects of interruption of HAART were tested in 2 patients. Viral load was measured by the Roche Amplicor assay. During HAART, in 12 of 15 patients a significant reduction of CSF HIV RNA concentration was observed, ranging from 0.55 to 2.77 log10 (median, 1.37 log10). This was paralleled by a reduction of blood viremia ranging from 0.12 to 3.0 log10 (median, 1.65 log10). The median half-life, as calculated from the slopes of the two time-point measurements, for CSF and blood viral load was 2.66 and 2.36 days, respectively. In 2 patients, CSF viral load remained essentially unchanged despite substantial reduction of plasma viral load. In 1 patient, after interruption of HAART, a rapid increase of HIV RNA in the CSF and blood was seen. No correlation was found between the CSF:blood albumin ratio as a measure of the functional integrity of the blood-CSF barrier and the ratio of CSF:blood RNA concentration, which suggests that no major passive influx of HIV RNA moves from the blood into the CSF compartment. However, a correlation existed between the CSF cell count and the CSF viral load (r = 0.74; p < .003). We conclude that, in most HIV-infected individuals, the decay of viral load in the CSF is similarly rapid as that seen in plasma. The rapid kinetics of virus found in the CSF suggest that it may be produced by rapidly proliferating cells, such as lymphocytes.