Steady-state pharmacokinetics of indinavir in cerebrospinal fluid and plasma among adults with human immunodeficiency virus type 1 infection.

To characterize steady-state indinavir pharmacokinetics in cerebrospinal fluid and plasma, 8 adults infected with human immunodeficiency virus underwent intensive cerebrospinal fluid sampling while receiving indinavir (800 mg every 8 hours) plus nucleoside reverse transcriptase inhibitors. Nine and 11 serial cerebrospinal fluid and plasma samples, respectively, were obtained from each subject. Free indinavir accounted for 94.3% of the drug in cerebrospinal fluid and 41.7% in plasma. Mean values of cerebrospinal fluid peak concentration, concentration at 8 hours, and area under the concentration-time profile calculated over the interval 0 to 8 hours [AUC(0-8)] for free indinavir were 294 nmol/L, 122 nmol/L, and 1616 nmol/L x h, respectively. The cerebrospinal fluid-to-plasma AUC(0-8) ratio for free indinavir was 14.7% +/- 2.6% and did not correlate with indexes of blood-brain barrier integrity or intrathecal immune activation. Indinavir achieves levels in cerebrospinal fluid that should contribute to control of human immunodeficiency virus type 1 replication in this compartment. The cerebrospinal fluid-to-plasma AUC(0-8) ratio suggests clearance mechanisms in addition to passive diffusion across the blood-cerebrospinal fluid barrier, perhaps by P-glycoprotein-mediated efflux.

Evidence of a source of HIV type 1 within the central nervous system by ultraintensive sampling of cerebrospinal fluid and plasma.

Defining the source of HIV-1 RNA in cerebrospinal fluid (CSF) will facilitate studies of treatment efficacy in the brain. Four antiretroviral drug-naive adults underwent two 48-hr ultraintensive CSF sampling procedures, once at baseline and again beginning on day 4 after initiating three-drug therapy with stavudine, lamivudine, and nelfinavir. At baseline, constant CSF HIV-1 RNA concentrations were maintained by daily entry of at least 10(4) to 10(6) HIV-1 RNA copies into CSF. Change from baseline to day 5 ranged from -0.38 to -1.18 log(10) HIV-1 RNA copies/ml in CSF, and from -0.80 to -1.33 log(10) HIV-1 RNA copies/ml in plasma, with no correlation between CSF and plasma changes. There was no evidence of genotypic or phenotypic viral resistance in either CSF or plasma. With regard to pharmacokinetics, mean CSF-to-plasma area-under-the-curve (AUC) ratios were 38.9% for stavudine and 15.3% for lamivudine. Nelfinavir and its active M8 metabolite could not be accurately quantified in CSF, although plasma M8 peak level and AUC(0-8hr) correlated with CSF HIV-1 RNA decline. This study supports the utility of ultraintensive CSF sampling for studying HIV-1 pathogenesis and therapy in the CNS, and provides strong evidence that HIV-1 RNA in CSF arises, at least in part, from a source other than plasma.

Association between delirium and death in AIDS patients.

The purpose of this study was to examine the relationship between delirium and death in AIDS patients. Forty-one patients admitted to a combination skilled nursing and assisted-living facility in 1994 were included in the retrospective chart review. Patients were grouped according to the presence versus absence of delirium during the first week of admission. Demographic characteristics and medical morbidity of the two groups were compared using the Chi-square statistic. Kaplan-Meier survival analysis was used to estimate survival functions during the study period for the delirious and nondelirious groups. Nine patients (22%) were found to have an episode of delirium in the first week of admission. There were no significant differences in demographic characteristics or medical morbidity between the delirious and nondelirious groups. Median days from admission to death for those with delirium (10 days) versus those without delirium (135 days) was significantly different (log rank = 19.03; p < 0.0001). Authors concluded that delirium is a marker for decreased survival in this sample of AIDS patients. Future research needs to demonstrate whether improved care of AIDS patients can prevent delirium or limit adverse outcomes associated with it.

Culture age and drying time as variables of the AOAC Sporicidal Test.

In the United States, the AOAC Sporicidal Activity of Disinfectants Method 966.04 is the standard for identifying a liquid chemical germicide as a sterilant. Furthermore, the highest level of a disinfectant must also be a sterilant as defined by Method 966.04, when used in its sterilant mode for a longer exposure time. The AOAC Sporicidal Test is also used as a part of the standard test methods to define a sterilant for Australia and the European Union. Many laboratories have identified variables of this test that can affect the sterilization exposure time for sterilants, or even the ability to classify a chemical as a sterilant. Method 966.04 requires spore-labeled porcelain penicylinders (cylinders) and silk suture loops, collectively referred to as carriers, to be dried for 24 h, but allows these carriers to be used for at least 7 days, in effect allowing a drying time of 24 h to at least 7 days. We tested the resistance of cylinders that had been labeled with Bacillus subtilis spores cultured for 72, 96, and 120 h, and dried for 24, 48, and 72 h against a 60 min exposure to 2.0% alkaline glutaraldehyde, and 2, 5, 10, 15, and 20 min exposures to 2.5N HCl. All the culture incubation and drying times met the standard of resistance to 2.5N HCI for at least 2.0 min at 20 degrees C, and all carriers contained at least 10(5) colony-forming units (CFU) of B. subtilis per carrier. However, for 3 repeated tests, regardless of incubation time, an average of 96% of the carriers were sterilized by the 2.0% glutaraldehyde after drying for 24 h, and an average of 61 % were sterilized after drying for 48 or 72 h. We propose that the variable of drying time be eliminated from Method 966.04.

Measuring level of function in mentally III prison inmates: a preliminary study.

The need to portray accurately the level of functioning and severity of psychiatric symptoms among mentally ill offenders (MIOs) is paramount from several perspectives. The prison environment may cast aspersions on the reliability and validity of commonly used functional assessment tools. In addition, these tools do not capture environment-specific areas that may be of interest to the courts, clinicians, community mental health centers, and other correctional facilities. Male MIOs (n = 61) who had been treated for at least three months in a (male) Washington state prison mental health program were evaluated using clinical assessment tools, data abstraction from medical records, and structured assessments from correctional officers. Clinical assessments occurred at their current site of incarceration. The semistructured clinical assessments had high construct validity and correlation for psychiatric symptoms and diagnosis. The ability of evaluators to determine accurately relative treatment compliance within the prison was low compared with the reports from correctional staff, particularly with respect to attendance at programs. In general, the officers did not recognize lack of program participation and reclusive behavior as potential signs of mental illness. Despite a significant history of psychiatric symptoms severe enough to warrant inpatient treatment, 70 percent of the MIO individuals were functioning reasonably well in a general population. A fully informed functional assessment of MIOs likely requires input from both clinicians and correctional officers.

Relationship between two dichotic listening tests and the Token test for children.

The relationship between two dichotic listening tasks was studied. The two dichotic tests used were the Staggered Spondaic Word (SSW) test and the directed Dichotic Consonant-Vowel (CV) test. These measures were administered to 104 children between the ages of 6.0 and 8.0 yrs. The subjects were divided into two groups according to their Token test scores with group I having normal Token test scores and group II having below average scores on the Token test. When the performances of the two groups on the SSW test were compared, a significant difference was found between them on the right and left competing conditions of the test. There was no difference between the groups on any response bias. On the directed Dichotic CV test the two groups were significantly different on the right ear scores but not on the left ear scores under both directed conditions. The groups were also significantly different on the directed right task when the difference between the two ear scores was compared but not on the directed left task. It was concluded that there is a relationship between these two dichotic measures and the Token Test for Children.

Outcomes associated with delirium in acutely hospitalized acquired immune deficiency syndrome patients.

The study demonstrates that delirium in acquired immune deficiency syndrome (AIDS) patients is associated with mortality, the need for long-term care, and an increased length of hospitalization. Data were collected prospectively on human immunodeficiency virus (HIV)/AIDS patients admitted to a teaching hospital from January 1996 through December 1996. The data included demographic characteristics of the participants, medical diagnoses, CD4 cell count, Karnofsky functional assessment, mortality during admission, length of stay, and discharge placement. Participants were evaluated throughout their hospital stay for evidence of delirium. The presence of delirium was determined using DSM-IV diagnostic criteria. There were no significant differences between delirious and nondelirious patients with respect to demographic characteristics or markers of medical morbidity. Patients with delirium were more likely to die during admission (chi-square [chi2] = 39.1, df = 1, P<.0010), to stay longer in hospital (t = 3.50, df = 12.9, P<.0041), or to need long-term care if discharged alive (chi2 = 12.8, df = 2, P<.0021). Delirium is associated with adverse outcomes in hospitalized AIDS patients. More research is needed to characterize the nature of this association.

Rearrest: does HIV serostatus make a difference?

Correctional facilities have become collection and containment centres for HIV-seropositive individuals. This is due to factors that affect incarceration in general: past criminal behaviour, age and crime type. In addition, the sex trade industry, intravenous drug use and community instability are likely factors affecting this particular population. The objective of this study was to determine whether HIV-positive offenders have higher rates of rearrest than HIV-negative offenders. A sample of HIV-positive offenders (n = 57) were seen for mental health evaluation at the King County Correctional Facility (KCCF) in Seattle Washington. They were compared to a historical sample (n = 254) of HIV-negative individuals also from the KCCF. After three months, 50% of both samples had been rearrested. Using the log rank test in Kaplan-Meier survival analysis, statistical difference in the relative risk of rearrest occurred for the HIV-positive group (logrank = 0.03). Statistical adjustment for mental illness, age, race, ethnicity, substance abuse history and past criminal history did not affect rearrest significantly. Nonetheless, HIV-positive individuals who presented with mental health needs appeared to be significantly more vulnerable to rearrest after the first three months of release into the community.

Comparison of Roche MONITOR and Organon Teknika NucliSens assays to quantify human immunodeficiency virus type 1 RNA in cerebrospinal fluid.

We compared Roche MONITOR and Organon Teknika NucliSens assays for human immunodeficiency virus type 1 (HIV-1) RNA in cerebrospinal fluid (CSF). Results of 282 assays were highly correlated (r = 0.826), with MONITOR values being 0.29 +/- 0.4 log(10) copies/ml (mean +/- standard deviation) values. Both assays can reliably quantify HIV-1 RNA in CSF.