Human immunodeficiency virus and papovavirus infections in acquired immunodeficiency syndrome: an ultrastructural study of three cases

A wide variety of neurologic conditions associated with the acquired immunodeficiency syndrome (AIDS) have been attributed to human immunodeficiency virus (HIV) infection of the central nervous system (CNS). Tissue samples from the brains of three patients with AIDS, diagnosed as having CNS toxoplasmosis on the basis of computed tomographic scans of the head, were studied by transmission electron microscopy. In two, HIV particles were observed budding from, in close association with, and in cytoplasmic vacuoles of mononuclear and multinucleated macrophages, but no other cell types. The patient with the greatest number of HIV particles also had large amounts of papovavirus (progressive multifocal leukoencephalopathy) in the nuclei of oligodendroglial cells and in the cytoplasm of astrocytes. These astrocytes often had atypical features at the light microscopic level. Following an initial biopsy that showed only HIV, primary CNS lymphoma was diagnosed by needle biopsy and confirmed at autopsy in a second case. A diagnosis of progressive multifocal leukoencephalopathy was rendered by transmission electron microscopy in a third case, but no HIV was detected. Toxoplasmosis was not confirmed in any of the three cases. Diagnosis of CNS lesions in patients with AIDS should not rely exclusively on radiography but include biopsy for both light and transmission electron microscopy. Transmission electron microscopy can be employed to reveal HIV and papovavirus infections not discernible at the light microscopic level and should be used as a diagnostic tool in HIV-related infections.     

Autopsy findings in AIDS — A histopathological analysis of fifty cases

Summary Fifty consecutive AIDS autopsy cases were evaluated. All subjects showed one or more opportunistic infections and malignancies included in the AIDS case definition with cytomegalovirus and Kaposi's sarcoma being most prevalent. Mycobacterial and cryptococcal infections occurred only infrequently. Most patients of our series after successful treatment ofPneumocystis carinii pneumonia or cerebral toxoplasmosis later succumbed to less treatable conditions like disseminated cytomegalovirus or fungal infections or malignant lymphoma. In the absence of specific treatment for the HIV infection leading to these lethal complications special emphasis must be put on the prevention of HIV transmission and spread.Abbreviations AIDS Acquired immune deficiency syndrome - CDC Centers for Disease Control - CMV Cytomegalovirus - CNS Central nervous system - HIV Human immunodeficiency virus - KS Kaposi's sarcoma - ML Malignant lymphoma - PCP Pneumocystis carinii pneumonia     

Neuropathology of the spinal cord in the acquired immunodeficiency syndrome.

The neuropathologic findings in the spinal cord were reviewed in 138 consecutive autopsies of patients with the acquired immunodeficiency syndrome. In all cases both the brain and spinal cord were examined by conventional histologic techniques, and in 63 cases immunohistochemistry was used to detect human immunodeficiency virus (HIV), Toxoplasma gondii, cytomegalovirus, and JC papovavirus antigens. The most common observation was a normal spinal cord (60%). Vacuolar myelopathy (VM) was observed in 23 (17%) cases. Human immunodeficiency virus myelitis was evident in 8% of cases. Human immunodeficiency virus myelitis was associated with HIV encephalitis in 65% of the cases. Opportunistic infections of the spinal cord were uncommon, consisting of cryptococcosis (five cases), cytomegalovirus (four cases), toxoplasmosis (one case), and progressive multifocal leukoencephalopathy (one case), and almost always were seen with cerebral and/or systemic infection by these agents. Malignant lymphoma rarely involved the spinal cord (four cases); all were B-cell lymphomas and were associated with cerebral and/or systemic lymphoma. Other abnormalities rarely observed were Wallerian degeneration of the corticospinal tracts or posterior columns (6%) and focal microinfarcts. Most cases of VM (78%) were not associated with HIV myelitis, and in the five patients with both VM and HIV myelitis, HIV-infected cells were not found in the regions affected by VM. In contrast, 65% of cases with VM were associated with HIV encephalitis. The pathogenesis of VM remains unknown; it is probably not due to direct infection by HIV.     

Detection of HIV-related protein in testes and prostates of patients with AIDS

The testes and prostates of 14 patients with acquired immune deficiency syndrome (AIDS) for whom autopsies were performed were examined for the presence of human immunodeficiency virus (HIV) and the pathologic alterations seen in AIDS. Histologically, the testes contained peritubular fibrosis and variable spermatogenic arrest, which were inconsistent with the young age of these patients. There were also numerous foci of germ cell degeneration and occasional germ cell loss. The Leydig cells were atrophic and decreased in number. The prostates contained increased numbers of concretions. Sections of testis and prostate were stained with an anti-HIV P17 monoclonal antibody with the use of the avidin-biotin technique. Small scattered foci of positive staining were identified in 8 of 14 testes (57%). They were located over one or several degenerating germ cells and the surrounding Sertoli cells. In addition, in 9 of 14 prostates (64%) there were a few minute foci of positive staining in several adjacent glandular epithelial cells. In one case the testis was positive and the prostate was negative, whereas in two cases the testes were negative and the prostate positive. In contrast, 22 testes and 22 prostates of control non-AIDS patients, read double-blind, were negative. The positive controls were HIV-infected tissue culture HUT 78 lymphoma cells in which there were many scattered positive cells. The results indicate the presence of focal HIV-associated protein in the testes and prostates of patients with AIDS, particularly within the foci of germ cell degeneration. The present observations are in accordance with previous research demonstrating the presence of HIV in the seminal fluid of patients with AIDS and appears to indicate the presence of an infection of the male genital tract by the HIV virus.     

Monocytoid B-cell lymphoma in a patient with human immunodeficiency virus infection. Demonstration of human immunodeficiency virus sequences in paraffin-embedded lymph node sections by polymerase chain reaction amplification

There is a significantly increased incidence of malignant lymphoma in patients with acquired immunodeficiency syndrome (AIDS). The lymphomas are usually of a high grade and of B-cell phenotype. While the frequent presence of reactive monocytoid B lymphocytes in patients with AIDS-related lymphadenopathy has recently been documented in several studies, to our knowledge, there are no reported cases of monocytoid B-cell lymphoma, the neoplastic counterpart of monocytoid B lymphocytes, in patients with AIDS. We now describe a human immunodeficiency virus (HIV)-positive patient with HIV-related lymphadenopathy in whom monocytoid B-cell lymphoma developed during the course of his disease. The morphologic and immunologic features of the lymphoma were characteristic of monocytoid B-cell lymphoma, and the involved lymph node exhibited a reversed CD4/CD8 ratio. Moreover, using the polymerase chain reaction, we were able to demonstrate HIV genome in DNA extracted from the lymph node tissue. To our knowledge, this is the first report of a case of monocytoid B-cell lymphoma occurring in an HIV-positive patient and in which we were able, by using a sensitive molecular biologic technique, to demonstrate HIV sequence in paraffin-embedded, fixed lymph node sections.     

Malignant lymphomas in HIV-seropositive patients. Frequency,features, and prognosis. Report on 31 cases

Summary In a random HIV-seropositive population, malignant lymphomas were diagnosed in 31 patients, of whom 24 (77%) had non-Hodgkin lymphoma (NHL) and 7 (23%) Hodgkin lymphoma (HL). The prevalence of NHL among AIDS patients was 8% (23/279 cases), with a prevalence of 17% among autopsied patients (16/96 cases). No patient with HL had AIDS at the time of diagnosis. In 7 of 23 AIDS patients with NHL (30%) the diagnosis was made only post mortem; among these were all 5 patients with primary CNS NHL. Median survival from the time of diagnosis was 1 month for patients with NHL and 3 months for those with HL. In individual patients, survival for several years may be possible with chemotherapy. Certain patients with NHL appear to benefit from intensive chemotherapy with a combination of methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOPB protocol). Appropriate, therapeutic strategies taking into account the patients' individual conditions, including the overall prognosis, urgently requires development. Metastatic CNS involvement, which was the primary cause of death in 5 of 11 patients with NHL (45%) receiving chemotherapy, represents a serious limitation to successful treatment.Abbreviations AIDS acquired immunodeficiency syndrome - CB centroblastic - CDC Centers for Disease Control - CHOP cyclophosphamide, doxorubicin, vincristine, prednisone - CMV cytomegalovirus - CNS central nervous system - COPBLAM cyclophosphamide, vincristine, prednisone, bleomycin, doxorubicin, procarbazine - COPP/ABVD cyclophosphamide, vincristine, prednisone, procarbazine/doxorubicin, bleomycin, vinblastine, darcarbazine - CR complete remission - CT computerized tomography - ELISA enzyme-linked immunosorbent assay - HIV human immunodeficiency virus - HL Hodgkin lymphoma - IT intrathecal - IMVP16 ifosfamide, methotrexate, etoposide - KC Kiel classification - MACOP-B methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, bleomycin - ML malignant lymphoma - NHL non-Hodgkin lymphoma - OI opportunistic infection - PCP Pneumocystis carinii pneumonia - PD progressive disease - PR partial remission - RT radiation therapy - WBC white blood cells - WF Working Formulation     

HIV encephalitis-like multinucleated giant cells in a nodal lymphoma in AIDS

A case of acquired immune deficiency syndrome (AIDS), in which multinucleated giant cells, characteristic of the human immunodeficiency virus (HIV)-encephalitis, were found in a mediastinal nodal deposit of lymphoma, is reported. Immunocytochemical studies confirmed the macrophage/histiocytic origin of these cells and the presence of HIV antigen in their cytoplasm. The occurrence of such multinucleated giant cells, representing the hallmark of HIV infection, has not been previously reported outside the central nervous system.     

Epstein-Barr viral load as a marker of lymphoma in AIDS patients

Epstein-Barr virus (EBV) is implicated in the pathogenesis of acquired immunodeficiency syndrome (AIDS) lymphoma, and viral DNA is present within the malignant cells in about half of affected patients. We examined the extent to which EBV viral load is elevated in the plasma of AIDS lymphoma patients compared to AIDS patients with opportunistic infections. Sixty-one AIDS patients were studied including 35 with lymphoma (24 non-Hodgkin, six Hodgkin, and five brain lymphoma) and 26 with various opportunistic infections. In situ hybridization revealed EBV encoded RNA (EBER) expression in the malignant cells of 17/28 AIDS lymphomas (61%). In 232 serial plasma samples from 35 lymphoma patients and in 128 samples from AIDS controls, EBV viral load was assayed by quantitative-polymerase chain reaction (Q-PCR) using a TaqMan probe targeting the BamH1W sequence. EBV was detected in plasma from all 17 EBER-positive AIDS lymphoma patients, with viral loads ranging from 34 to 1,500,000 copies per ml (median 3,210). Viral load usually fell rapidly upon initiation of lymphoma therapy and remained undetectable except in two patients with persistent tumor. In 11 AIDS patients, whose lymphoma lacked EBER expression, and in 26 control patients without lymphoma, levels of EBV in plasma were usually low or undetectable (range 0-1,995 and 0-2,409, median 0 and 0, respectively). There was no association between EBV viral load and human immunodeficiency virus (HIV) load or CD4 count. In conclusion, EBV viral load shows promise as a tool to assist in diagnosis and management of EBV-related lymphoma patients.     

Pathogenesis of HIV encephalitis

A wide spectrum of infectious agents attack the central nervous system (CNS) of acquired immunodeficiency syndrome (AIDS) patients. Human immunodeficiency virus (HIV) itself, infects the CNS of a subgroup of these patients. The mechanism behind why HIV enters the CNS is unclear. We have observed an interesting association between HIV and opportunistic viral infections that may explain why HIV enters the brain. Infection of the CNS by opportunistic agents results in recruitment of latently HIV-infected monocytes. Upon differentiation into macrophages these cells produce abundant HIV. Latent HIV-infection of monocytes/macrophages provides a unique opportunity for cooperativity between opportunistic infections and HIV in mediating CNS damage.     

Pathogenesis of HIV Encephalitis

A wide spectrum of infectious agents attack the central nervous system (CNS) of acquired immunodeficiency syndrome (AIDS) patients. Human immunodeficiency virus (HIV) itself, infects the CNS of a subgroup of these patients. The mechanism behind why HIV enters the CNS is unclear. We have observed an interesting association between HIV and opportunistic viral infections that may explain why HIV enters the brain. Infection of the CNS by opportunistic agents results in recruitment of latently HIV infected monocytes. Upon differentiation into macrophages these cells produce abundant HIV. Latent HIV-infection of monocytes/macrophages provides a unique opportunity for cooperativity between opportunistic infections and HIV in mediating CNS damage.     

Cytology of pericardial effusions in aids patients

Pericardial effusions in patients with the acquired immunodeficiency syndrome (AIDS) can be due to a variety of causes and are often large enough to be sampled for cytologic examination. Over a period of 46 months, 15 cytologic specimens from 14 patients with AIDS were examined. Thirteen patients were male, one was female; the age range was 26 to 43 years. All male patients were homosexual or intravenous drug abusers, and the female patient was the spouse of an intravenous drug abuser. In general, the cytology specimens were moderately cellular with inflammatory cells seen in all cases. Atypical or reactive mesothelial cells were found in 12 cases (80%), and the atypia in one of these 12 was so marked that carcinoma was suspected; cells suspicious for malignant lymphoma were found in 2 cases (13%); degenerated mesothelial cells were present in one case. No infections were identified in this series. Ten patients (66%) had subsequent pericardial biopsies. Marked cellularity and nuclear pleomorphism in lymphoid cells with an altered nuclear cytoplasmic ratio were the dominant findings in the two suspected lymphoma cases. Both patients had known lymphoma elsewhere; in one, involvement by lymphoma was also found on pericardial biopsy. Mesothelial proliferations showing papillary formations with psammoma bodies were seen in three cases; in one of these, histoplasmosis was later diagnosed by pericardial biopsy. To our knowledge this is the first series to describe cytologically the marked mesothelial atypia seen in pericardial fluid in AIDS patients. We contrast this atypia with that seen in malignant effusions and caution against overinterpretation of pericardial fluids from AIDS patients.     

Clinical profile of AIDS: a study at a referral hospital

The present study describes the clinical and epidemiological features of 74 patients with human immunodeficiency virus (HIV) infection who presented to a referral hospital. Sixty two patients (83.7%) were diagnosed to have acquired immune deficiency syndrome (AIDS). Mean age of the patients was 34.9 +/- 12 years and male to female ratio was 3:1. Majority of patients (80%) were from lower socio-economic class. Multiple unprotected heterosexual contact with commercial sex workers in metropolitan cities of India, mainly Mumbai, was major risk factor in 82.1% male patients while most of the females (66.6%) had acquired infection from HIV positive husbands. Blood transfusion was the risk factor in 9(12.1%) patients. Sixty eight patients were infected with HIV 1, one with HIV 2, and five patients with both HIV 1 and HIV 2. Fever and weight loss were the commonest presenting symptoms. Tuberculosis, oropharyngeal candidiasis, and interstitial pneumonitis were present in 54.8%, 40.3% and 20.9% patients, respectively. Fourteen patients (22.5%) had generalised lymphadenopathy. Herpes zoster, cryptococcal meningitis, and peripheral neuropathy were infrequent. Response to standard antifungal and antitubercular treatment was satisfactory. Kaposi's sarcoma, lymphoma, and CNS toxoplasmosis were not found. The clinical manifestations of AIDS patients are strikingly different from that in the Western countries. It, thus, necessitates setting up of different guidelines for the clinical diagnosis and management of AIDS in India.     

Low grade gastric B-cell lymphoma of mucosa associated lymphoid tissue in immunocompromised patients

An increased incidence of non-Hodgkin's lymphoma is seen in patients with immunodeficiency from any cause. The majority of these are high grade B-cell lymphoma and most are associated with the Epstein-Barr virus (EBV). In post-transplant lymphoma/lymphoproliferative disorders the tumour may regress following reduction of immunosuppression but in AIDS the lymphomas show a characteristic aggressive course and poor prognosis. We describe low grade B-cell gastric lymphoma of mucosa associated lymphoid tissue (MALT) in three immunocompromised patients (two post-transplant, one HIV positive). In each case, the tumour showed classical morphological features of gastric MALT lymphoma and was not associated with EBV. Helicobacter pylori was identified in each case. Clinical follow-up suggests that the behaviour in these tumours is similar to that seen in MALT lymphomas in immunocompetent patients and not typical of the lymphomas usually associated with immunosuppression. Although the finding of MALT lymphoma in immunosuppressed patients might be coincidental, the association of some MALT lymphomas with autoimmune disease suggests that dysregulation of the immune system might play a role in the pathogenesis of these tumours.     

From the archives of MD Anderson Cancer Center: Primary effusion lymphoma with simultaneous involvement of the retroperitoneum and pleural cavity

Primary effusion lymphoma (PEL) is a rare neoplasm that arises in the context of severe immunosuppression. Acquired immunodeficiency syndrome (AIDS) as a result of human immunodeficiency virus (HIV) infection is the most common cause of immunodeficiency in patients who develop PEL. These neoplasms usually involve one or more body cavities, so-called classic PEL. The pleural cavity is most often involved, followed by the peritoneal and pericardial cavities. Involvement of the cerebrospinal fluid (CSF) and meninges is rare. A subset of patients can present with a tissue-based mass, known as the extracavitary variant. We encountered a patient with HIV infection and severe immunosuppression who presented initially with mediastinal, retroperitoneal mass and bilateral pleural effusions. He subsequently developed CSF involvement. Despite therapy, the patient relapsed with chest wall disease 6 months later and died shortly thereafter. Our literature review yielded about 400 cases of PEL reported previously. About 65 % of PEL patients have had AIDS, but a subset of patients had immunosuppression attributable to organ transplantation or physiological immunosenescence. CSF involvement has been reported in ~2 % of patients, and about 10 % of patients had both body cavity and extracavitary disease. The pathologic findings in this case were typical of extracavitary PEL. The neoplastic cells had features of plasmablasts and were positive for HHV-8, Epstein-Barr virus encoded RNA (EBER) and plasma cell associated markers, and were negative for B-cell antigens. The prognosis of patients with PEL is usually poor with a median survival less than one year in most studies. We use this patient's case as an illustration of PEL and we review the clinicopathologic findings and differential diagnosis of PEL.     

Epstein-Barr and human immunodeficiency viruses in acquired immunodeficiency syndrome-related primary central nervous system lymphoma.

The prevalence of Epstein-Barr virus (EBV) and human immunodeficiency virus (HIV) in acquired immunodeficiency syndrome (AIDS)-related primary central nervous system (CNS) lymphoma was examined. Deoxyribonucleic acid (DNA) extracted from 12 formalin-fixed, paraffin-embedded tumors was used as substrate for the polymerase chain reaction (PCR). Targets for amplification were the EBNA-1 region of EBV, the gag region of HIV, and a single copy cellular sequence as a control. The cases studied were autopsy and surgical specimens collected between the years 1985 and 1989. By the working formulation for non-Hodgkin's lymphomas, five had large cell, four had mixed large and small cleaved cell, two had small cleaved cell, and one had an unclassified histology. Epstein-Barr virus was detected in 6 of 12 tumors studied. Human immunodeficiency virus was not detected in any of the tumors. The presence of EBV was not correlated with any particular histologic tumor type. It is concluded that EBV, not HIV, can be detected in a large percentage (50%) of AIDS-related primary central nervous system (CNS) lymphomas. This viral association may be significant in light of the demonstrated ability of EBV to induce lymphoid tumors in experimental mammalian systems.     

Neuropathologic findings in 13 deceased patients with acquired immunologic deficiency syndrome

The neuropathological findings in 13 patients with the acquired immune deficiency syndrome (AIDS) and with AIDS related complex (ARC) are reported. Six patients presented with neurological symptoms, whereas autopsy revealed CNS involvement in nine cases. Four patients showed neither neurological nor neuropathological abnormalities. The most frequent neuropathological diagnoses were toxoplasma encephalitis (4 cases) and multiple or solitary cerebral necroses (3 cases). Long tract degeneration of the spinal cord was found in 2 cases. Cytomegalovirus infection, progressive multifocal leukoencephalopathy, primary lymphoma of the CNS, infiltration of the leptomeninges by plasmocytoma cells and a solitary metastasis of a bronchial carcinoma were diagnosed in one case each. Subacute leukoencephalitis, mentioned frequently in the literature, was not present in this material. In one case, however, status spongiosus and gliosis was found in the cortex and basal ganglia. As similar spongy changes can be seen in mice infected experimentally with retroviruses, a pathogenetic role of the human T-cell lymphotropic/leukaemia virus type III (HTLV-III) cannot be ruled out. Astrogliosis and hypertrophy of astrocytes were found in nine cases. Morphometrically, the number of astrocytes was significantly higher in AIDS patients than in control cases which were selected randomly on grounds of comparable age. Whether this finding bears some relationship with HTLV-III encephalopathy remains open to further investigation. Glial nodules were found in four cases; according to silver impregnation they were composed of microglial elements.     

Role of human immunodeficiency virus and cytomegalovirus in AIDS encephalitis.

Approximately half of patients with advanced acquired immune deficiency syndrome (AIDS) develop a subcortical dementia. The brains of all autopsies on AIDS patients performed at UCSD between 1982 and 1986 (N = 93) were studied. Neuropathologic changes consistent with a viral encephalitis were present in 54 brains (58%). Human immunodeficiency virus (HIV) antigens were detected in 37 of the brains (40%), most frequently in macrophages, multinucleated giant cells, and endothelial cells. Cytomegalovirus (CMV) was detected in 31 of the brains (33%), 22 of which also contained HIV. Cellular localization of CMV antigens suggests that CMV disseminates to the central nervous system hematogenously where the virus can infect endothelial cells, glia, and neurons. While the temporal course of the appearance of these two viruses within the CNS is not clear, the common simultaneous occurrence of both viruses within the brains of AIDS patients suggests that in vivo interaction between them may play a role in the pathogenesis of AIDS-associated encephalitis. Given the significant neurologic symptoms described in AIDS patients, the paucity of viral antigens suggests a pathogenic mechanism of indirect CNS damage rather than direct viral infection.     

Kaposi''s sarcoma among AIDS patients: Transmissible venereal tumour by cell engraftment?

The epidemiologic findings of Kaposi's sarcoma (KS) among patients with the acquired immunodeficiency syndrome (AIDS) suggest that human immunodeficiency virus (HIV) infection is insufficient for the development of KS. It was speculated that another sexually transmitted infection is responsible for the markedly increased incidence of KS among patients who acquired HIV infection through sexual intercourse. However, no such contributing infectious agent was consistently identified. The canine transmissible venereal tumour (TVT) is a malignant tumour that can be transplanted by viable cells across major histocompatibility complex (MHC) barriers. Recent findings suggest that all canine TVTs originated from the same tumour and were transferred from one animal to the other during sexual intercourse. It is suggested that, in analogy with the canine TVT model, the characteristics of KS epidemic among AIDS patients may be explained by transmission and engraftment of viable malignant cells during intercourse.     

Neuropathology of the central nervous system in acquired immune deficiency syndrome (AIDS) in Japan. With special reference to human immunodeficiency virus-induced encephalomyelopathies

The neuropathological features of the central nervous system in 15 autopsy cases of Japanese male with AIDS were reported. Nine patients had various histological changes including a variety of opportunistic infections in six patients (40%), primary malignant lymphoma of the brain in two (13%), AIDS encephalopathy in four (27%) and vacuolar myelopathy in one (7%). Usually, these pathological changes were present concomitantly. AIDS encephalopathy was characterized by infiltration of mono- and multinucleated cells and myelin pallor with astrogliosis located predominantly in the cerebral white matter and subcortical gray matter. Furthermore, unevenly distributed neuronal loss of the cerebral cortex was apparent in one case. Diffuse astrocytosis of the gray matter out of proportion to neuronal loss was also an outstanding finding in another case. The present study suggested that not only the white matter changes but also gray matter alterations might be the morphological substrates of AIDS encephalopathy.     

An autopsy case of acquired immune deficiency syndrome (AIDS) with preceding aplastic anemia

A case of acquired immunodeficiency syndrome (AIDS) with preceding aplastic anemia is reported. The patient was a 36 year old female who had been diagnosed as having aplastic anemia 10 years before and thereafter had received multiple transfusions. Human immunodeficiency virus (HIV)-seropositivity was revealed 10 months prior to her death, but no particular clinical signs indicating HIV infection, pre-AIDS or onset of AIDS were recognized before serological diagnosis, although the slow progression of leukopenia was noted along with thrombocytopenia. Her general condition deteriorated during the last 10 months accompanied by an acute decrease In the CD4/CD8 ratio. Autopsy revealed full-blown AIDS: systemic aspergillosis, progressive multifocal leukoencephalopathy, Epstein-Barr virus-related B cell lymphoma arising in the diaphragm and severe lymphocyte depletion in the lymph nodes and spleen. Markedly hypo-plastic bone marrow was considered to be primarily attributable to the aplastic anemia but the affection of AIDS was not excluded. The possible transmission route of HIV and the effect of the preceding aplastic anemia on the infection and clinical course of AIDS are discussed.