Virological markers in the cerebrospinal fluid from HIV-1-infected individuals.

We analysed 127 specimens of cerebrospinal fluid (CSF) from 118 HIV-1-infected individuals at different stages of infection. Intrathecal antibody synthesis was evident in 23 samples tested and was more frequently directed against HIV than against rubella virus, herpes simplex virus, varicella zoster virus or cytomegalovirus. HIV was isolated from only 14% of the 127 CSF specimens, but from 82% of CSF-paired blood samples. HIV antigen was detected in 12% of CSF specimens and 44% of paired plasma samples. Twenty specimens analysed using the polymerase chain reaction (PCR) detected proviral DNA in 75% of CSF specimens. The low rate of virus recovery from CSF was caused by neither the freezing of specimens prior to culture nor therapy. In contrast, virus isolation from CSF was significantly associated with CSF cell count. Virus isolation and antigen detection in CSF were not correlated with either the Centers for Disease Control disease stage or the peripheral CD4+ lymphocyte count, whereas viraemia was significantly associated with a low CD4+ lymphocyte count. Moreover, virus isolation and antigen detection in CSF were not associated with symptoms of subacute HIV encephalitis, suggesting that these markers are not of potential value in the diagnosis of HIV-specific neurologic complications. The value of PCR in this field merits further investigation.

Human immunodeficiency virus type 1 antigen in cerebrospinal fluid. Correlation with clinical neurologic status.

Human immunodeficiency virus type-1 (HIV-1) antigen was assayed in paired serum/cerebrospinal fluid (CSF) specimen from 85 adults and 58 children with acquired immunodeficiency syndrome and was compared with clinical neurological status. A quantitative comparison of HIV-1 antigen levels in matched serum and CSF specimens indicated that HIV-1 antigen expression in these compartments is independent and is correlated with acquired immunodeficiency syndrome dementia complex in adults and progressive encephalopathy in children. In a longitudinal study (n = 47), 16 patients tested positive for HIV-1 antigen in the CSF before (n = 2) or coincident (n = 14) with neurological deterioration. Six patients who tested positive for HIV-1 antigen in the CSF remained neurologically normal for a median duration of follow-up of 11 months. Six of 25 patients who tested negative for HIV-1 antigen in the CSF, subsequently showed neurological deterioration. These data indicate that HIV-1 antigen expression in the CSF is not useful in predicting neurological deterioration.

Evaluation of the AIDS dementia complex in clinical trials.

The AIDS dementia complex (ADC) is one of the most common and important causes of morbidity associated with infection by human immunodeficiency virus type 1 (HIV-1). The evaluation of ADC in clinical trials is significant not only because of the clinical impact of this syndrome, but also because of the value of measuring its cardinal features as an index of drug efficacy and because of its emerging role as a major clinical end point. The objectives of therapy include both prevention of ADC in the presymptomatic patient and alleviation of established disease. At present, the pathogenesis of ADC is incompletely understood in several critical aspects, particularly the processes underlying the clinical manifestations of central nervous system (CNS) HIV-1 infection and, further, how such processes are related to systemic disease. Consequently, it is not yet clear to what extent, or in which patients, it is necessary to achieve "therapeutic" drug levels within the CNS. Nevertheless, the assessment of ADC prevention and treatment relies principally on the complementary approach of neurological examination for diagnosis and neuropsychological testing for quantitative serial measurement of treatment effects. Additionally, surrogate markers in cerebrospinal fluid (CSF) may hold promise for objective, rapid assessment of treatment response and dose adjustment. Other measurements, including more routine CSF analysis, neuroimaging, and neurophysiological assessments, are used principally for differential diagnosis rather than for monitoring ADC status. Accumulating experience with available antiviral agents suggests that ADC can be effectively prevented and treated, at least for some period of time, and that assessment of this condition is indeed a valuable approach for measuring antiviral therapy.

Detection of antibodies against myelin basic protein and increased levels of HIV-IgG antibodies and HIV antigen after solubilization of immune complexes in sera and CSF of HIV infected patients.

Fifteen HIV seropositive patients were studied. It was possible to enhance detection of HIV antigen and HIV and myelin basic protein (MBP) antibodies after dissociation of immune complexes by acid hydrolysis. HIV p24 antigen was then detected in four patients, three of whom were previously antigen negative. In 14 patients the treatment resulted in increased anti-HIV IgG subclass levels. Anti-MBP IgG was detected in 12 patients. Intrathecal synthesis of anti-MBP IgG subclasses was found in eight patients, five of whom had symptoms from the central nervous system.

Declining incidence of AIDS dementia complex after introduction of zidovudine treatment.

OBJECTIVE: To assess the incidence of the AIDS dementia complex and the presence of HIV I p24 antigen in cerebrospinal fluid in relation to zidovudine treatment. DESIGN: Retrospective study of a consecutive series of patients with AIDS from 1982 to 1988. SETTING: An academic centre for AIDS. PATIENTS: 196 Patients with AIDS and neurological symptoms examined from 1982 to 1988. INTERVENTIONS: Zidovudine treatment, which was introduced to The Netherlands on 1 May 1987 for patients with severe symptoms of HIV infection (Centers for Disease Control groups IVA, B, C, and D). MAIN OUTCOME MEASURES: Diagnosis of AIDS dementia complex and presence of HIV I p24 antigen in cerebrospinal fluid. RESULTS: The AIDS dementia complex was diagnosed in 40 of the 196 (20%) patients with AIDS. Thirty eight of 107 patients with AIDS (36%) not taking zidovudine developed the AIDS dementia complex compared with two of the 89 (2%) taking the drug (p less than 0.00001). The incidence of the AIDS dementia complex increased to 53% in the first half of 1987, after the introduction of zidovudine in May 1987, decreasing to 10% in the second half of 1987 and to 3% in 1988. Dementia was diagnosed before definition of the AIDS dementia complex (1986) according to DSM-III criteria and there was good agreement between diagnosis before and after 1986. Sixteen of 61 samples of cerebrospinal fluid (26%) from patients with AIDS (10 with the AIDS dementia complex) not taking zidovudine were positive for HIV I p24 antigen, whereas none of 37 cerebrospinal fluid samples from patients with AIDS (two with the AIDS dementia complex) taking zidovudine were positive. CONCLUSIONS: The incidence of AIDS dementia complex in patients with AIDS declined after the introduction of systematic treatment with zidovudine; the AIDS dementia complex might be prevented by inhibiting viral replication in the central nervous system.

[Comparative study of 2 commercial tests for the detection of HIV-1 antigens in blood and cerebrospinal fluid using immunoenzymology]. / Etude comparative de deux trousses commerciales pour la recherche de l'antigène HIV I en immunoenzymologie (EIA) dans le sérum et le liquide céphalorachidien.

The authors have carried out, on 150 sera of patients seropositive for the human immunodeficiency virus type I (HIV I) and 11 cerebrospinal fluid of which 5 were patient infected by the HIV I, a comparative study of two commercial tests for the detection of HIV I antigen (Diagnostic Pasteur and Abbott laboratories). A much greater sensitivity was obtained with the specificity being practically identical for the sera with the two tests (100% with Abbott laboratories test, 96.11% with the diagnostic Pasteur test). 4 sera appeared "false negatives" with the Abbott Laboratories test; their optical density was situated between 80 and 100 p. cent of the cut-off level value, whereas that of the "real" negatives was situated between 30 and 60 p. cent of the cut-off level value. 10 of the 11 cerebrospinal fluids appeared false positive with the Diagnostic Pasteur. This seems to be connected with an insufficiency of saturation of protein receptors in the wells. The Diagnostic Pasteur test is not adapted for the detection of HIV I antigen in the body fluids with a weak protein concentration. Contrary to the results obtained with the Encavor test (Abbott laboratories) the analysis in western-blot does not show an inverse prevalence of anti p24 GAG antibodies with regard to antigen HIV I in seropositive patients. On the other hand, the statistical analysis of the positive HIV I sera which are at the same time antigen HIV I positive and antibodies HIV I positive suggests an earlier disappearance of anti p17 GAG antibodies than of anti p24 GAG antibodies.

HIV1-Ag in cerebrospinal fluid during AIDS.

HIV infection may display neurological symptoms at any stage; the virus can be isolated from the cerebrospinal fluid (CSF) of both symptomatic and asymptomatic patients and of two third of patients with AIDS. This study sought to determine the sensitivity of HIV1-Ag in the CSF of an HIV-Ab positive population to evaluate its diagnostic and/or prognostic significance. CSF HIV1-Ag was dosed in 48 patients: 9 patients belonged to the III CDC group, 2 to group IVA, 1 to IVB and 36 to IVC1. In the last group, 14 patients had not opportunistic infections of the CNS. The tests proved positive in: 1 IVB patient and 16 IVC patients with focal lesions of the CNS or cerebral atrophy; HIV1-Ag was present in the CSF of 63% of patients displaying neurologic symptoms and it reached 84% in patients with diffuse CNS pathology.

[Prevalence of HIV antigens in cerebrospinal fluid and in serum of patients with both asymptomatic and symptomatic HIV infection]. / Wystepowanie antygenów HIV w plynie mózgowo-rdzeniowym i w surowicy u osób z bezobjawowym i objawowym zakazeniem HIV.

Prevalence of HIV-Ag in both serum and CSF has been determined in 19 HIV infected patients, including 7 patients without any symptoms or only generalized lymphadenopathy, 5 patients with ARC and 7 patients with AIDS. The results have been correlated with clinically evident neurological disorders. HIV-Ag have been detected in 9 out of 12 patients with ARC (AIDS Related Complex) and AIDS. In 8 of them neurological disorders have been present. Out of the remaining 7 patients in only one HIV-Ag has been detected in CSF (p < 025). No correlation between the presence of HIV antigen in CSF and serum has been noted.

Neurological features in AIDS patients: studies on cerebrospinal fluid.

The relationship between cerebrospinal fluid (CSF) markers of HIV infection and the spectrum of neurological manifestations were studied in 15 AIDS patients (13 with and 2 without confirmed neurological disorders). We demonstrated the presence of intrathecally synthesized anti-HIV antibodies. Antibodies to HIV envelope proteins were present in all patients but those to HIV core proteins in 9/13 cases only. HIV antigen and HIV p24 antigen were present in 6/14 and 4/12 cases respectively. HIV was not isolated from 6 samples of CSF. We have demonstrated that CSF markers of HIV infection were present in all AIDS patients, with or without neurological manifestations. Moreover HIV p24 antigen seems to be a very reliable marker of HIV infection.

[Detection of HIV antibody and antigen].

A total of 75 specimens (45 sera, 17 CSF and 13 stool) was collected from 65 participants (39 AIDS, 14 high risk group and 12 laboratory personnel) and HIV antibody and antigen were detected. Twenty sera and 16 CSF submitted by AIDS patients showed positive antibody reactions in both ELISA and Western blot assay, whereas, antibody was not detected in the sera and the CSF obtained from high risk group or laboratory personnel. An overall of 21% (10/48) positive rate was found in the specimens submitted by AIDS patients for HIV antigen detection by ELISA. The positive rates of HIV antigen in sera, CSF and stool specimen from the AIDS patients were 30% (6/20), 13% (2/16) and 17% (2/12), respectively.

Immunocytochemical demonstration of human immunodeficiency virus infected cells in the cerebrospinal fluid.

Although involvement of the central nervous system represents one of the most common manifestations of the acquired immunodeficiency syndrome (AIDS), a standard diagnostic test for this condition has not yet been established. At necropsy human immunodeficiency virus (HIV) has been demonstrated in brain macrophages in such patients. HIV antigen was detected in CSF macrophages by immunocytochemistry in six out of 11 HIV infected patients. In addition to the detection of intrathecal synthesis of anti-HIV antibodies this method may be suitable for early diagnosis of CNS involvement in AIDS patients.

Comparison of spinal fluid beta 2-microglobulin levels with CD4+ T cell count, in vitro T helper cell function, and spinal fluid IgG parameters in 163 neurologically normal adults infected with the human immunodeficiency virus type 1.

Beta 2-microglobulin levels were measured in the cerebrospinal fluid (CSF) and serum of 163 human immunodeficiency virus-positive (HIV+) persons with normal neurologic physical examinations. None were on antiretroviral therapy. Only 3% had a positive CSF HIV p24 antigen test. The CSF beta 2-microglobulin levels increased as the CD4+ T cell count decreased. Intrathecal production of beta 2-microglobulin was suggested by finding CSF concentrations greater than serum concentrations in 15% of patients. The CSF beta 2-microglobulin levels rose as in vitro T helper cell function deteriorated, independent of CD4+ T cell count. CSF beta 2-microglobulin levels paralleled CSF IgG, IgG index, and IgG synthesis. Higher CSF beta 2-microglobulin levels were found in persons with positive CSF oligoclonal bands. CSF beta 2-microglobulin concentration may serve as a marker for subclinical neurologic damage due to HIV. If this is established, defining the effect of anti-HIV interventions on CSF beta 2-microglobulin would be warranted.

Elevated alpha-tumor necrosis factor levels in spinal fluid from HIV-1-infected patients with central nervous system involvement.

To assess the role of alpha-tumor necrosis factor in the pathogenesis of central nervous system involvement during human immunodeficiency virus type 1 infection, we recorded clinical data and measured alpha-tumor necrosis factor levels in serum and cerebrospinal fluid samples from 45 patients infected with human immunodeficiency virus type 1, classified as group II/III (10), group IV A (5), group IV B (10), and group IV C-1 (20) of the Centers for Disease Control acquired immunodeficiency syndrome classification system and 42 controls. Alpha-tumor necrosis factor was above the limit of detection in only 3 of 15 sera and 3 of 15 cerebrospinal fluid samples from patients in group II/III and group IV A, whereas it was detected in 17 of 30 sera (p less than 0.05) and 22 of 30 cerebrospinal fluid (p less than 0.0002) samples from clinically more advanced patients (group IV B and group IV C-1). Alpha-tumor necrosis factor mean values were 21.5 pg/ml in sera and 50.0 pg/ml in cerebrospinal fluid from group IV B patients and 30.4 pg/ml in sera and 24 pg/ml in cerebrospinal fluid from group IV C-1 patients.(ABSTRACT TRUNCATED AT 250 WORDS)