Clinical predictors for the aetiology of peripheral lymphadenopathy in HIV-infected adults.

OBJECTIVES: The aim of the study was to determine the aetiology and clinical predictors of peripheral lymphadenopathy in HIV-infected individuals during the antiretroviral (ARV) era in a nontuberculosis endemic setting. METHODS: A multicentred, retrospective cohort study of peripheral lymph node biopsies in HIV-positive adults was carried out. A total of 107 charts were identified and reviewed for clinical features, lymphadenopathy size, and ARV use and duration. Biopsy results were categorized, and multivariate logistic regression determined independent predictors of lymphadenopathy aetiology. RESULTS: Evaluation of 107 peripheral lymph node biopsies revealed that 42.9% of peripheral lymphadenopathy was attributable to malignancy, 49.5% to reactive changes, and 7.5% to infections, with only 2.8% of all cases secondary to tuberculosis. Fevers, weight loss, ARV use, and lower viral loads are significantly associated with nonreactive lymphadenopathy. CONCLUSIONS: Lymphadenopathy is likely to be reactive or malignant in nontuberculosis endemic regions. Readily available clinical features can aid clinicians in predicting the underlying aetiology, those at risk for malignancy, and who to biopsy.

[Clinical and laboratory characteristics of HIV-infection in servicemen].

HIV-infection in Russia and its Armed Forces is a serious threat to the national health and country's safety. Study of peculiarities of disease spread in the military collectives and HIV-infection manifestation is an actual problem. HIV-infection is diagnosed during the latent stage in all categories of servicemen and characterized by unchanged function of cellular and humoral immunity. In most servicemen with HIV-infection the disease course has a form of co-infection with parenteral hepatitis B and C.

Malignancy in HIV/AIDs: a single hospital experience.

BACKGROUND AND OBJECTIVES: Our hospital serves an area with a significant number of patients seropositive for the human immunodeficiency virus (HIV). Intravenous drug abuse and heterosexual exposure are by far the predominant risk factors for HIV and acquired immunodeficiency syndrome (AIDS). Seven percent of these patients develop malignancies. Our aim was to study the types of tumor, their distribution, and to evaluate the patients' outcome. METHODS: Of 3,578 patients with HIV infection or AIDS treated between 1993 and 1998, 245 had 1 or more malignancies. Information was collected on age, sex, race, predisposing risk factors for AIDS, malignancies, symptoms at presentation, the time of the onset of AIDS, CD4 cell counts, pathology findings, and mortality. RESULTS: Although aspects of our patients resembled those of previously studied groups of patients with AIDS, there also were ways in which our patients differed from those other groups. Of our patients, 21. 6% had non-AIDS-defining (NAD) invasive malignancies. This was considerably higher than the rate in most studies. Twenty-seven patients with such malignancies died during the study. Forty-two other patients had pre-invasive cancers. Among patients having AIDS-defining (AD) malignancies, 55.9% died, a fact that was related to patients' low CD4 cell counts and late presentation. Our 97 patients with Kaposi sarcoma included 22 women, a relatively high number that may be related to the fact that most of our patients were intravenous drug abusers or had become infected by heterosexual transmission of HIV. CONCLUSIONS: AIDS is associated with a high risk of malignancy and an unusual spectrum of tumors. Patients with invasive tumors have advanced disease at the time of initial presentation. Those with AD tumors have a worse prognosis than patients with NAD tumors. The impact of highly active antiretroviral therapy on both AD and NAD tumors needs to be further evaluated.

Antibody to the ligand for CD40 (gp39) inhibits murine AIDS-associated splenomegaly, hypergammaglobulinemia, and immunodeficiency in disease-susceptible C57BL/6 mice.

Infection of genetically susceptible C57BL/6 mice with the LP-BM5 isolate of murine retroviruses cause profound splenomegaly, hypergammaglobulinemia, lymphadenopathy, and an immunodeficiency syndrome which includes the development of terminal B-cell lymphomas. Because many of these and the other manifestations of LP-BM5 virus-induced disease are similar to those seen in AIDS, this syndrome has been named murine AIDS, or MAIDS. Previous reports have shown that the onset of MAIDS depends on the presence of both CD4+ T cells and B cells and have suggested that CD4+ T-cell-B-cell interactions are important to disease pathogenesis. Here, we assessed the possibility that interactions between CD40 and its ligand on activated CD4+ T cells, CD40 ligand/gp39, are involved in the development of MAIDS. To test this hypothesis, LP-BM5-infected B6 mice were treated in vivo with anti-gp39 monoclonal antibody. As a result, MAIDS-associated splenomegaly, hypergammaglobulinemia, germinal center formation, and the loss of in vitro responsiveness to the T- and B-cell mitogens concanavalin A and lipopolysaccharide were inhibited. Anti-gp39 monoclonal antibody-treated LP-BM5-infected mice were also able to mount essentially normal alloantigen-specific cytolytic T-lymphocyte responses. These results support the possibility that molecular interactions between CD40 and gp39 are critical to the development of MAIDS.

[Pathogenesis of neurological disorders in AIDS].

Impairment of the central nervous system (CNS) and peripheral nervous system (PNS) is common during the human immunodeficiency virus type 1 (HIV-1) infection. There are evidences of activated immune reactions in the CNS and PNS of patients with acquired immunodeficiency syndrome (AIDS). The expression of HIV-1 predominantly in monocyte/macrophage lineage cells strongly suggests immunopathogenetic mechanisms. Possible mechanisms of neuronal and glial cell damage include calcium dependent excitotoxicity by HIV-1 envelope protein, N-methyl-D-aspartate (NMDA) receptor-mediated neurotoxicity of quinolinic acid, injury of oligodendrocytes by tumor necrosis factor--alpha, cell injury by HIV-1-specific cytotoxic T cells, and apoptosis of oligodendrocytes or neurons. These mechanisms are not mutually exclusive. Multiple factors may be involved in the pathogenesis of HIV-1-associated neurological diseases.

Natural history of HIV infection in Filipino female commercial sex workers.

A prospective follow-up study of the progression of HIV infection, from seroconversion to onset of opportunistic infections (OI) indicative of immune deficiency and to death, was performed in a cohort of 54 HIV-1 antibody positive Filipino female commercial sex workers (FCSW). The cumulative probability of having a CD4+ T cell count of < 200/mm3 and/or an OI indicative of severe immune deficiency was 52.9% within 5 years and 73.8% within 6 years after seroconversion. The cumulative probability of death was 52.1% within 6.5 years following seroconversion and 52.7% within 1.5 years after a depressed (< 200/mm3) CD4+ T cell or onset of an OI. Although several OI associated with immune impairment were observed, a CD4+ cell count of < 200/mm3 was the initial indicator of a failing immune system in more than 50% of the patients. Mycobacterium tuberculosis or unidentified acid fast bacilli (presumed to be M. tuberculosis) and Pneumocystis carinii pneumonia were the initial indicators of immune deficiency in the remaining patients.

Hallazgos de necropsia en 51 casos de SIDA con daño cardiovascular / Autopsy findings of 51 cases of AIDS with cardiovascular damage

El propósito del estudio es describir las alteraciones cardiovasculares encontradas en las necropsias de 51 pacientes con diagnóstico de SIDA, así como la patología intercurrente encontrada en estos casos reunidos entre enero de 1988 y agosto de 1993. Se encontró derrame pericárdico en 9 casos, derrame pleural en 7, miocarditis en 5, pericarditis en 7, endocarditis en 6, hipertrofia ventricular izquierda en 20, hipertrofia ventricular derecha en 21 y evidencia de aterosclerosis en 15 más. El 42.7 por ciento de los enfermos tuvieron algún dato de afección caridovascular. Las alteraciones cardiovasculares en este grupo de pacientes son frecuentes, pero su detección clínica es escasa: se tuvo tal sospechas en vida sólo en el 12 por ciento de los casos. Es necesario, entonces, un examen físico detallado con estudios orientados a la detección oportuna de esas alteraciones.

Virus-specific cytotoxic T-lymphocytes in HIV-2-infected cynomolgus macaques.

OBJECTIVE: Specific cytotoxic T-lymphocytes (CTL) are induced in humans or monkeys after infection with HIV-1 or SIVmac, respectively. Since, like HIV-1, HIV-2 causes AIDS, our objective was to determine the characteristics of the HIV-2-specific CTL response. DESIGN: Since it is rarely possible to study cellular immunity in individuals, because of the small number of HIV-2-infected patients available in Europe and the necessity for co-operation in the performance of sequential CTL assays, cynomolgus macaques were infected with HIV-2. Autologous transformed B-lymphoblastoid cell lines infected with recombinant vaccinia viruses were used as target cells for cytotoxicity assays. METHODS: Recombinant vaccinia viruses expressing HIV-2 genes were constructed to infect B-lymphoblastoid cell lines from macaques. These cells were used as target cells for cytotoxicity assays with peripheral blood mononuclear cells from HIV-2BEN-infected cynomolgus macaques. To characterize the effector cells, CD8+ cells were separated with immunomagnetic beads. Major histocompatibility complex (MHC) restriction of the cytotoxic cells was determined by incubation with matched or mismatched target cells. RESULTS: HIV-2BEN-infected cynomolgus macaques raised CTL against proteins of the three major viral structural genes, gag, pol and env. The cytotoxic cells were CD8+ and their activity was MHC class I-restricted. In contrast to SIVmac-infected macaques, env-specific lysis was mediated exclusively by CD8+ cells. CTL from individual animals recognized different viral proteins and the recognition pattern varied over time. CONCLUSIONS: Like HIV-1 and SIVmac, HIV-2 induces virus-specific CTL. The variation of antigen recognition between individual animals and over time indicates that sequential experiments are necessary to determine the complete spectrum of the CTL response of infected animals. HIV-2-infected macaques represent a suitable model for investigations into the cellular immune response against HIV.

Natural history of advanced HIV disease in patients treated with zidovudine. The Zidovudine Epidemiology Study Group.

OBJECTIVE: To describe the natural history of advanced HIV disease in patients treated with zidovudine. DESIGN: Longitudinal, observational study. SETTING: Twelve academic and community-based sites. PATIENTS, PARTICIPANTS: Eight hundred and sixty-three patients with AIDS or AIDS-related complex (ARC) with a CD4+ lymphocyte count less than 250 x 10(6)/l, who first received zidovudine between 15 April 1987 and 14 April 1988. MAIN OUTCOME MEASURES: Survival, progression to AIDS and first development of specific opportunistic illness. RESULTS: Median survival after initiation of zidovudine therapy ranged from greater than 900 days in patients with a baseline CD4+ lymphocyte count greater than or equal to 150 x 10(6)/l to 560 days in patients with a CD4+ lymphocyte count less than 50 x 10(6)/1. Other factors associated significantly with poorer survival were diagnosis of AIDS (versus ARC), baseline age greater than or equal to 40 years, hematocrit less than 35%, and diminished functional status. In patients with ARC at enrollment, median time of progression to AIDS ranged from 810 days in patients with a CD4+ lymphocyte count greater than or equal to 150 x 10(6)/l to 310 days in patients with a CD4+ lymphocyte count less than 50 x 10(6)/l. Rates of development of specific opportunistic infections or neoplasms and HIV encephalopathy were determined for different baseline CD4+ lymphocyte count ranges. Myelosuppression was significantly more common in patients with CD4+ lymphocyte counts greater than or equal to 100 x 10(6)/l. Sixty-five per cent of patients with a CD4+ lymphocyte count greater than or equal to 100 x 10(6)/l and 51% with a CD4+ lymphocyte count less than 100 x 10(6)/l continued to receive zidovudine 2 years after starting therapy. CONCLUSIONS: We describe the natural history of a cohort of patients treated with zidovudine for advanced HIV disease. These CD4+ lymphocyte count-stratified estimates of disease progression should provide prognostic information useful in the clinical management of advanced disease and the design of future studies.

[AIDS and tuberculosis: the immunopathogenic processes]. / SIDA si tuberculoza: procese imunopatogene.

HIV infection is characterized by CD4+ lymphocyte depletion manifested through the loss of the immune response capacity. The resulting immunodeficit is expressed by the blocking of immune surveillance mechanisms and, thus, by the establishment of favourable conditions to the development of opportunistic infections and/or malignant processes. In tuberculosis, the immunodeficiency associated with HIV infection makes possible the evolution of a latent infection to a clinically manifest disease. Latent tuberculosis is characterized by the intracellular persistence of some metabolically inactive Tb bacillus forms which are incapable of multiplication. The conversion of these inactive into metabolically active forms capable of multiplication is usually neutralized by immunosurveillance mechanisms. The blocking of such mechanisms in case of CD4+ cell depletion will allow the multiplication of metabolically active Tb bacillus forms, and the development of a clinically manifest tuberculosis. CD4+ lymphocyte depletion is the result of facilitating antibodies and certain cytokines, and of some autoimmune processes which also affect the non-infected CD4+ cells. Therefore, it is necessary that Tb chemoprophylaxis in HIV infected subjects should also be addressed to the processes initiating the immune deficit, which include autoimmune mechanisms as well as those facilitating HIV infection.

Malignant lymphoma associated with human AIDS and with SIV-induced immunodeficiency in macaques.

Malignant lymphomas associated with human (HIV) and simian (SIV) immunodeficiency virus infections are reviewed and compared. Recent observation of a high frequency of lymphomas in a series of cynomolgus macaques, highly immunodeficient after infection with SIVsm(smm3) are described. In addition to the increased frequency in human and monkey AIDS, SIV and HIV lymphomas share several important features. Clinically and by histology they present as aggressive high-grade malignant tumors with a predilection for extranodal growth in viscera, skin, central nervous system, testis, and retroorbitally. Most malignant lymphomas are of B-cell origin. AIDS lymphomas in humans are heterogeneous with regard to Epstein-Barr virus (EBV) association. Similarly, most lymphomas in monkeys experimentally infected with SIV tested to date were shown to be associated with an EBV-like simian herpes virus. These observations point to the possibility of using SIV-immunodeficient macaques for study of EBV and other oncogenic and immunosuppressive factors in AIDS-associated lymphomagenesis.

[Clinico-experimental study of mental processes in men with HIV infection]. / Kliniko-éksperimental'noe issledovanie psikhicheskikh protsessov u muzhchin, infitsirovannykh VICh.

A total of 55 males aged 19.5 to 62 years who were infected with HIV were examined psychopathologically+ and neuropsychologically by A.R. Luria's methods. Twenty-one of these patients were homosexuals. Syphilis was recorded in 34.7% in this group. Lymphadenopathy was the major clinical sign of HIV infection. Symptoms of organic involvements+ of the central nervous system were revealed by a psychopathological method. Neuropsychological studies detected dysfunction of the right cerebral hemisphere, particularly in a group of homosexuals suffering from syphilis.

Central nervous system involvement in human immunodeficiency virus disease. A prospective study including neurological examination, computerized tomography, and magnetic resonance imaging.

Sixty-seven patients with different stages of human immunodeficiency virus (HIV) infection (47 CDC group IV, 20 CDC groups II or III) were followed prospectively for a median of 18 months with neurological examination, magnetic resonance imaging (MRI), and computerized tomography (CT) to evaluate the incidence of the AIDS dementia complex (CDC definition) and other neurological complications. Ten patients developed CNS opportunistic infection or malignancy. Among the remaining 57 patients, 12 of 37 (32%) belonging to CDC group IV, and 1 of 20 (5%) belonging to CDC groups II/III developed the AIDS dementia complex (p = 0.03). MRI white matter lesions occurred in 32% of CDC group IV patients and 5% of CDC groups II/III patients (p = 0.03). The corresponding figures for brain atrophy at CT were 71% and 30% (p less than 0.01) and for neurologic signs 49% and 20% (p = 0.06). The development of the AIDS dementia complex was significantly associated with the occurrence of MRI white matter lesions and a CD4 cell count of less than 200 x 10(6)/l, whereas it was not statistical significantly associated with brain atrophy at baseline. It is concluded that the AIDS dementia complex is a common feature of late stage HIV infection. Brain atrophy occurs in a large percentage of HIV infected patients, but the clinical significance of this atrophy is not clear.

[HIV infection and acquired immunodeficiency syndrome. I]. / Infezione da HIV e sindrome da immunodeficienza acquisita. Nota I.

This is the first of three articles on AIDS, in which the story of HIV infection, its etiology and pathogenesis, its pathology and clinical features, and finally its hygienic-prophylactic measures will be reviewed in the light of our present knowledge. Although the subject has been amply illustrated by many writers, it has been deemed useful to review it in this journal in order to present readers with an account of what is known so far and what must be the subject of further rapidly evolving research.

T4+ cell depletion as a major risk factor for AIDS-related complex and AIDS. Longitudinal study of 253 HIV-antibody positive heroin addicts from northern Italy.

We enrolled 253 HIV-antibody positive heroin addicts without HIV-related disease (n = 81) or with persistent generalized lymphadenopathy (n = 172) in a prospective study to evaluate clinical progression to AIDS related complex (ARC) or AIDS and to identify factors of possible prognostic relevance. Follow-up lasted between 6 and 40 months (median 12 months). According to the non-parametric Cox's model the only significant (P less than 0.001) prognostic variable was T4+ cell count considered in three classes: greater than 800/microliters (no depletion), 400-800/microliters (moderate depletion) and less than 400/microliters (absolute depletion). Subjects with T4+ cell count of less than 400/microliters had a risk of developing ARC or AIDS that was 6.46 and 1.98 higher than those with values of greater than 800/microliters or between 400 and 800/microliters respectively. The estimated probability of progression to ARC or AIDS was 0.029, 0.056 and 0.172 at one year in subjects with T4+ cell count of greater than 800/microliters 400-800/microliters and less than 400/microliters, respectively, and 0.296, 0.501, and 0.896 at two years.

[Transfusion-associated HIV infections in Switzerland 1982-1989]. / Transfusions-assoziierte HIV-Infektionen in der Schweiz 1982-1989.

Up to summer 1987, 19 patients who had acquired HIV infection by blood transfusion had been recorded in Switzerland. In the subsequent period, up to 1989, a further 15 patients with transfusion-associated HIV infection were recorded. In December 1989, 7 of these patients were asymptomatic, 4 had ARC, 5 Aids and 11 had died of Aids. One patient died of another disease and no detailed records were available in 6. It is estimated that some 170 persons may have been infected with HIV by transfusion in Switzerland before anti-HIV testing was introduced in fall 1985. Of these only 31% (20%) are recorded today. The average incubation time from infection to diagnosis of Aids was 54 months. The 11 patients who died of Aids had mean survival of 57 months after diagnosis of the disease. In 6 instances HIV-infected blood recipients have transmitted the disease to their sexual partners.