CD4+ CD25+调节性T细胞在HIV/AIDS患者中的作用及其与HIV病毒载量的相关性研究

目的 研究HIV感染者／AIDS患者外周血CD4^＋ CD25^＋ 调节性T细胞（CD4^＋ CD25^＋ regulatory Tcell，Treg）频率、功能及其临床意义。方法 选择31例HIV感染者／AIDS患者和30例健康对照者，采用流式细胞仪检测各组外周血Treg的表型和频率。采取MACS磁珠分选CD4^＋CD25^＋T细胞，利用[^3H]胸腺嘧啶掺入法检测CD4^＋ CD25^＋T细胞在特异性HIV抗原刺激下对CD4^＋ CD25-T细胞的增殖影响。结果HIV／AIDS患者组与正常对照组相比较，外周血CD4^＋ CD25^＋ T细胞频率在统计学上差异无统计学意义。与正常对照组比较，HIV感染者外周血CD4^＋ CD25^＋ T细胞频率升高，差异有统计学意义（P〈0.01）；与正常对照组比较，AIDS患者者外周血CD4^＋ CD25^＋ T细胞频率降低，差异有统计学意义（P〈0．0001）。HIV RNA病毒载量与患者外周血CD4^＋ CD25^＋ T细胞数量呈正相关性（P〈0．01）。CD4^＋ CD25^＋ T细胞具有抑制HIV特异性的CD4^＋ CD25^- T细胞的增殖作用。结论HIV感染者／AIDS患者的细胞免疫功能紊乱，CD4^＋ CD25^＋ T细胞能抑制HIV感染者／AIDS患者的HIV特异性细胞免疫反应，促进HIV病毒复制，与形成持续HIV感染有关。     

The effects on survival of early treatment of human immunodeficiency virus infection.

BACKGROUND. Zidovudine has been shown to prolong survival in patients with the acquired immunodeficiency syndrome (AIDS) and, in persons with human immunodeficiency virus (HIV) infection but not AIDS, to delay the progression to AIDS. However, it is still uncertain whether treatment before the development of AIDS prolongs survival. METHODS. We analyzed data from a cohort of 2162 high-risk men who were already seropositive for HIV type 1 (HIV-1) and 406 men who seroconverted from October 1986 through April 1991. There were 306 deaths. The probabilities of death were compared among men at similar stages of disease who began zidovudine therapy before the diagnosis of AIDS and among those who did not. Relative risks of death were calculated for each of five initial disease states on the basis of CD4+ cell counts and clinical symptoms and signs appearing over follow-up periods of 6, 12, 18, and 24 months. Adjustments were also made for the use of prophylaxis against Pneumocystis carinii pneumonia (PCP). RESULTS. After we controlled for CD4+ cell count and symptoms, the use of zidovudine with or without PCP prophylaxis before the development of AIDS significantly reduced mortality in all follow-up periods. The relative risks of death were 0.43 (95 percent confidence interval, 0.23 to 0.78) at 6 months, 0.54 (95 percent confidence interval, 0.38 to 0.78) at 12 months, 0.59 (95 percent confidence interval, 0.44 to 0.79) at 18 months, and 0.67 (95 percent confidence interval, 0.52 to 0.86) at 24 months. After we adjusted for the effects of PCP prophylaxis, zidovudine alone significantly reduced mortality at 6, 12, and 18 months (relative risks, 0.45, 0.59, and 0.70, respectively), but not at 24 months (relative risk, 0.81). Among zidovudine users, those who also used PCP prophylaxis before the development of AIDS had significantly lower mortality at 18 and 24 months than those who did not (relative risks, 0.62 and 0.60, respectively). CONCLUSIONS. The results of this study support the hypothesis that in HIV-1 infection, early treatment with zidovudine and PCP prophylaxis improves survival in addition to slowing the progression to AIDS.     

Susceptibility pattern and molecular type of species-specific Candida in oropharyngeal lesions of Indian human immunodeficiency virus-positive patients

A study of oropharyngeal candidiasis (OPC) in Indian human immunodeficiency virus (HIV)/AIDS patients was conducted over a period of 15 months. This study revealed that 75% of the HIV/AIDS patients had OPC. MIC testing revealed that 5% of the Candida isolates were fluconazole resistant. A correlation between CD4(+)-T-cell counts and development of OPC in HIV/AIDS patients was also observed. Molecular typing of C. albicans isolates showed that all were genetically unrelated.     

Clinical manifestations and the problems of classification of HIV infection]

The clinical manifestations and some immunological parameters (CD4 lymphocytes, CD4/CD8 ratio, IgM, IgA, IgG levels, skin test) were examined in 226 adult patients (148 males and 78 females) infected with HIV. These included 58 (26%) asymptomatic patients with seropositive test, 109 (48%) with the only clinical manifestation generalized lymphadenopathy; 54 (24%) with AIDS-related infections, 5 (2%) with AIDS. A subsequent follow-up of 3 months to 3 years demonstrated that AIDS developed in 7 patients, 9 died. The period of infection with HIV and death ranged from 1.5 to 9 years. The signs of cell immunodeficiency were found in 70% of the examinees. Recommendations are given on the classification of HIV infection.     

Persistent replication of human immunodeficiency virus type 1 despite treatment of pulmonary tuberculosis in dually infected subjects

Tuberculosis (TB) is the most common life-threatening infection in human immunodeficiency virus (HIV)-infected persons and frequently occurs before the onset of severe immunodeficiency. Development of TB is associated with increased HIV type 1 (HIV-1) viral load, a fall in CD4 lymphocyte counts, and increased mortality. The aim of this study was to examine how treatment of pulmonary TB affected HIV-1 activity in HIV-1/TB-coinfected subjects with CD4 cell counts of >100 cells/mul. HIV-1/TB-coinfected subjects were recruited in Kampala, Uganda, and were monitored over time. Based upon a significant (0.5 log10 copies/ml) decrease in viral load by the end of treatment, two patient groups could be distinguished. Responders (n = 17) had more rapid resolution of anemia and pulmonary lesions on chest radiography during TB treatment. This group had a significant increase in viral load to levels not different from those at baseline 6 months after completion of TB treatment. HIV-1 viral load in nonresponders (n = 10) with TB treatment increased and at the 6 month follow-up was significantly higher than that at the time of diagnosis of TB. Compared to baseline levels, serum markers of macrophage activation including soluble CD14 decreased significantly by the end of TB treatment in responders but not in nonresponders. These data further define the impact of pulmonary TB on HIV-1 disease. HIV-1 replication during dual HIV-1/TB infection is not amenable to virologic control by treatment of TB alone. Concurrent institution of highly active antiretroviral treatment needs to be evaluated in patients dually infected with pulmonary TB and HIV-1.     

Human immunodeficiency virus type 1 antigenaemia is enhanced in patients with disseminated cytomegalovirus infection and deficient T lymphocytes.

We have studied 61 patients with the acquired immunodeficiency syndrome (AIDS) regarding the relationships between disseminated cytomegalovirus (CMV) infection with CMV retinitis, HIV1 antigenaemia and CD4+ and CD8+ T-cell deficiency. HIV1 p24 antigenaemia was present in all patients with CMV retinitis (at a high concentration), but in only 28% of patients without retinitis (at a low concentration). Compared to patients without retinitis, those patients who developed retinitis had lower CD4+ and CD8+ prior to and during AIDS. CMV may contribute to deficiencies of T lymphocytes in patients with AIDS.     

Childhood AIDS nephropathy: a 10-year experience.

The objective of this study was to define the demographic, immunologic, and clinical characteristics of children with acquired immunodeficiency syndrome (AIDS) and AIDS nephropathy, and contrast this with the existing adult data. Data from 62 pediatric patients with AIDS who were treated at SUNY Health Science Center, Brooklyn, New York, between 1983 and 1993 were analyzed. Human immunodeficiency virus (HIV) infection was acquired during the neonatal period by vertical transmission (n = 60) or blood transfusion (n = 2). All children with AIDS who exhibited clinical nephropathy died (n = 16), with mean survival of 55.3 months. In contrast, 32 of 56 AIDS patients (70%) who did not manifest nephropathy were alive at the end of the study period. Patients with nephropathy were noted to have significantly lower CD4+ lymphocyte counts than those without nephropathy. These observations suggest that the predominant renal lesion in pediatric patients who acquired HIV infection during the perinatal period is focal segmental glomerulosclerosis, although a variety of other histological lesions were present. As in adults, the survival in children is dismal following the onset of clinical renal disease. In contrast to the adult population in whom multiple risk factors can potentially contribute to AIDS-associated nephropathy, occurrence of nephropathy in children with vertical HIV transmission provides convincing evidence for the pathogenetic role of HIV infection.     

A controlled trial of early versus late treatment with zidovudine in symptomatic human immunodeficiency virus infection. Results of the Veterans Affairs Cooperative Study.

BACKGROUND. Zidovudine is recommended for asymptomatic and early symptomatic human immunodeficiency virus (HIV) infection. The best time to initiate zidovudine treatment remains uncertain, however, and whether early treatment improves survival has not been established. METHODS. We conducted a multicenter, randomized, double-blind trial that compared early zidovudine therapy (beginning at 1500 mg per day) with late therapy in HIV-infected patients who were symptomatic and had CD4+ counts between 0.2 x 10(9) and 0.5 x 10(9) cells per liter (200 to 500 per cubic millimeter) at entry. Those assigned to late therapy initially received placebo and began zidovudine when their CD4+ counts fell below 0.2 x 10(9) per liter (200 per cubic millimeter) or when the acquired immunodeficiency syndrome (AIDS) developed. RESULTS. During a mean follow-up period of more than two years, there were 23 deaths in the early-therapy group (n = 170) and 20 deaths in the late-therapy group (n = 168) (P = 0.48; relative risk [late vs. early], 0.81; 95 percent confidence interval, 0.44 to 1.59). In the early-therapy group, 28 patients progressed to AIDS, as compared with 48 in the late-therapy group (P = 0.02; relative risk, 1.76; 95 percent confidence interval, 1.1 to 2.8). Early therapy increased the time until CD4+ counts fell below 0.2 x 10(9) per liter (200 per cubic millimeter), and it produced more conversions from positive to negative for serum p24 antigen. Early therapy was associated with more anemia, leukopenia, nausea, vomiting, and diarrhea, whereas late therapy was associated with more skin rash. CONCLUSIONS. In symptomatic patients with HIV infection, early treatment with zidovudine delays progression to AIDS, but in this controlled study it did not improve survival, and it was associated with more side effects.     

Phenotypic distribution of T cells of patients who have subsequently developed AIDS

In a previous study of asymptomatic homosexual men, we found that CD8+ T-cell levels were higher in homosexual men infected with the human immunodeficiency virus (HIV) than in uninfected homosexual men because of higher numbers of CD8+ T cells that do not express the Leu15 marker, a phenotype associated with cytotoxic function. Among infected men, there was a positive correlation between the number of CD8+Leu15- T cells and the number of CD4+ T cells. If CD4+ T-cell levels are taken as a measure of severity of HIV infection and immunodeficiency, these results suggested that higher CD8+Leu15- cells may represent a phenotypic profile associated with less severe infection or better control of infection. In the present study, we extend the analysis to include a group of men who progressed to AIDS but were studied well before the onset of AIDS, and we compare results of CD8 subset analyses with results of infected men who have not progressed to AIDS. Phenotypic subsets associated with helper, suppressor, cytotoxic, and natural killer cell function were determined by two-color immunofluorescence. The only phenotypic subset that distinguished men who progressed to AIDS from those who have not was lower numbers of CD4+ T cells in the former group. If CD8+Leu15- cell numbers (or other phenotypic subsets examined) reflect effective control of HIV infection, the relationship is not strong enough to be of prognostic or predictive value with respect to outcome of infection.     

Human immunodeficiency virus (HIV) infection in the regular sexual partners of homosexual men with AIDS and persistent generalised lymphadenopathy

Thirty-five homosexual men who had been the regular sexual partners (for at least 6 months) of anti-HIV-positive patients with AIDS (N = 18) or PGL (N = 17) were studied. Twenty-one (60%) were seropositive, but 14 (40%) were consistently anti-HIV-negative. The duration of relationship with the index case was not statistically different in seropositive compared to seronegative partners; median 26 months (range 7-60) vs 30 months (range 7-60). However, seropositive partners had a significantly higher monthly number of other sexual partners and sexually transmitted diseases and a higher frequency of insertive and receptive anal intercourse in the preceding five years. The risk of acquiring HIV infection was significantly increased by frequent receptive anal intercourse when the frequency of insertive was controlled for but not the converse. Seronegative partners had undetectable antibodies by live and fixed cell immunofluorescence and by radioimmunoprecipitation and were repeatedly negative by competitive enzyme immunoassay. Furthermore, the sera of seronegative partners lacked HIV neutralising activity. Peripheral blood mononuclear cells (PBMCs) from seronegative partners, stained with monoclonal antibodies to seven different CD4 epitopes, revealed no differences when compared to those from heterosexual controls and no qualitative differences from cells from seropositive individuals. In addition, PBMCs from seronegative partners could be productively infected by HIV in vitro. If resistance to infection in seronegative partners exists, then it is likely that mechanisms other than a specific humoral immunity or CD4 polymorphisms are involved.     

Genetic lesions in a preleukemic aplasia phase in a child with acute lymphoblastic leukemia

In a small fraction ( approximately 2%) of cases of childhood acute lymphoblastic leukemia (ALL) clinical presentation of leukemia is preceded, some 2-9 months earlier, by a transient, remitting phase of nonclassical aplastic anemia, usually in connection with infection. The potential "preleukemic" nature of this prodromal phase has not been fully explored. We have retrospectively analyzed the blood and bone marrow of a child who presented with aplastic anemia 9 months before the development of ETV6-RUNX1 fusion gene positive ALL. High resolution SNP genotyping arrays identified 11 regions of loss of heterozygosity, with and without concurrent copy number changes, at the presentation of ALL. In all cases of copy number change, the deletion or gain identified by single nucleotide polymorphism (SNP) analysis was confirmed in the ALL blasts by FISH. Retrospective analysis of aplastic phase bone marrow showed that the ETV6-RUNX1 fusion was present along with all of the additional genetic changes assessed, albeit subclonal to ETV6-RUNX1. These data identify for the first time the leukemic genotype of an aplasia preceding clinical ALL and indicate that multiple secondary genetic abnormalities can contribute to a dominant subclone several months before a diagnosis of ALL. These data have implications for the biology of ALL and for management of similar patients.     

Use of the polymerase chain reaction for early detection of the proviral sequences of human immunodeficiency virus in infants born to seropositive mothers. New York City Collaborative Study of Maternal HIV Transmission and Montefiore Medical Center HIV Perinatal Transmission Study Group

The early diagnosis of infection with human immunodeficiency virus (HIV) in infants born to infected mothers is essential for early treatment, but current tests cannot detect HIV infection in newborns because of the presence of maternal antibodies. We used the polymerase chain reaction, a new technique that amplifies proviral sequences of HIV within DNA, to detect HIV infection in peripheral-blood mononuclear cells obtained from infants of seropositive women during the neonatal (age less than 28 days) and postneonatal periods. In blood obtained during the neonatal period, the polymerase chain reaction was positive in five of seven infants in whom the acquired immunodeficiency syndrome (AIDS) later developed (a mean of 9.8 months after the test). The test was also positive in one of eight newborns who later had nonspecific signs and symptoms suggestive of HIV infection (mean follow-up, 12 months). No proviral sequences were detected in neonatal samples from nine infants who remained well (mean follow-up, 16 months). HIV proviral sequences were detected in samples obtained during the postneonatal period (median age, five months) in all of 6 infants tested who later had AIDS and in 4 of 14 infants with nonspecific findings suggestive of HIV infection. No proviral sequences were detected in 25 infants who remained well (mean follow-up, 17 months) after being born to HIV-seropositive mothers, or in 15 infants born to HIV-seronegative mothers. We conclude that the polymerase chain reaction will be a useful technique to diagnose HIV infection in newborns and to predict the subsequent development of AIDS. However, larger studies will be required to determine the sensitivity and specificity of the test.     

Tuberculous lymphadenitis associated with human immunodeficiency virus (HIV) in Uganda.

Sixteen adults presented with lymphadenopathy which was tuberculous on biopsy; they were all seropositive for human immunodeficiency virus (HIV-1), but none had the clinical criteria of the acquired immunodeficiency syndrome (AIDS). The biopsy specimen showed caseating tuberculosis, with scanty or no visible acid fast bacilli in seven cases; the remaining nine had a poor cellular reactivity with numerous bacilli. Antituberculous chemotherapy for two months reduced the lymphadenopathy. Two patients subsequently developed AIDS. Mycobacterial cultures were not performed, but the infection was almost certainly Mycobacterium tuberculosis. The space-time clustering of tuberculous lymphadenitis now seen in Kampala, and the unusual non-reactive histopathology, are typical of the impairment of cellular immunity induced by HIV infection.     

Expansion of activated T lymphocytes (CD3+HLA/DR+) detectable in early stages of HIV-1 infection

Summary The phenotypic characterization of lymphocyte subsets in relation to different clinical stages of HIV infection has mainly focussed on CD4 and CD8 cells. Some reports focus on expansion of activated T lymphocytes in AIDS patients. Yet there is no detailed knowledge whether such changes occur also in earlier stages of HIV infection. In order to describe the kinetics and possible pathogenetic meaning of this subset when related to all distinct chronologic stages, we performed two-color flow cytometric lymphocyte differentiation in 173 HIV-infected patients and 30 healthy controls. All subjects were classified according to the Walter Reed (WR) system. Our results show that a significant increase of activated T lymphocytes (CD3+HLA/DR+) occurs early, in WR1 and WR2, thus preceding the clinically relevant CD4 depletion. This increase is paralleled by an expansion of CD 8+Leu7+cytotoxic cells. We conclude, thatearly changes of lymphocyte subsets are detectable in addition to inversion of the CD4/ CD8 ratio. The possible pathogenetic meaning including the question of possible autoimmune mechanisms is discussed.Abbreviations AIDS acquired immunodeficiency syndrome - ARC AIDS-related complex - CD cluster of differentiation - FITC fluorescein isothiocyanate - HIV human immunodeficiency virus - MAB monoclonal antibodies - NK natural killer - PBMC peripheral blood mononuclear cells - PE phycoerythrin - SEM standard error of the mean     

Prevalence and correlates of anemia in a large cohort of HIV-infected women: Women's Interagency HIV Study

Anemia is a common manifestation of HIV infection, occurring in approximately 30% of patients with asymptomatic infection and in as many as 75% to 80% of those with AIDS. Anemia has been associated with decreased quality of life and decreased survival. We performed a cross-sectional study nested within a multicenter prospective cohort study to describe the prevalence of anemia in 2056 HIV-infected and 569 HIV-negative women as well as to define the demographic, clinical, immunologic, and virologic correlates of anemia among HIV-infected women. A total of 37% of HIV-positive women and 17% of HIV-negative women had hemoglobin levels < 12 g/dl (p < .001). Factors associated with anemia in HIV-positive and HIV-negative women included mean corpuscular volume (MCV) < 80 fl (p < .001) and black race (p < .001). Among HIV-infected women, multivariate logistic analyses revealed that African American race (p < .0001), MCV < 80 fl (p < .0001), CD4 count < 200 per microliter (p <.0001), higher HIV RNA in plasma (p = .02), current use of ZDV (p = .01), and history of clinical AIDS (p = .004) were all independent predictors of anemia. These data indicate that worsening parameters of HIV disease are associated with anemia among HIV-infected women. Black women and women with low MCV values are at increased risk for anemia independent of HIV status.     

High-dose intravenous immunoglobulins in the treatment of adolescent and adult HIV-infected hemophiliacs

In children infected with human immunodeficiency virus (HIV) placebo-controlled trials with intravenous immunoglobulins have resulted in a significant reduction in morbidity; however, the results of small trials in adolescents and adults have been inconsistent. In this study 17 HIV-infected hemophiliacs aged 9–30 years were treated with monthly intravenous immunglobulins for an average of 32 months. At the end of the study, 8 years after the HIV infection, three patients (18%) had progressed to the acquired immunodeficiency syndrome(AIDS), and the average decrease in CD4 cells was 81 cells/l per year. The natural history of HIV infection in hemophiliacs in this age group shows a manifestation rate of AIDS between 11 and 26% 6–8 years after seroconversion and an average yearly decrease in CD4 lymphocytes of 68–110 cells/l. In conclusion, we observed no difference either in the manifestation rate of AIDS or in prognostic markers in this small cohort of HIV-infected hemophiliacs treated for more than 30% of their latency period with intravenous immunoglobulins compared to the well-documented natural history of HIV-infected hemophiliacs. However, none of the patients developed severe bacterial infections during the study period.Abbreviations AIDS acquired immunodeficiency virus - HIV human immunodeficiency syndrome     

Serum and effector-cell antibody-dependent cellular cytotoxicity (ADCC) activity remains high during human immunodeficiency virus (HIV) disease progression

The activity of both serum and effector cell antibody-dependent cellular cytotoxicity (ADCC) against human immunodeficiency virus (HIV-1, HIV) was assessed in HIV-infected individuals. The goal was to relate ADCC levels with the stage or progression of HIV disease. Serial serum samples, usually collected at 6-month intervals, from individuals at defined stages of HIV disease (sero-conversion, the HIV-seropositive period before AIDS, and around the time of clinical AIDS diagnosis) were tested. HIV-coated CEM tumor cells were used as targets. Effector-cell ADCC activity was evaluated using fresh peripheral blood mononuclear cells (PBMC) from HIV-infected individuals at different stages of HIV disease. Samples were obtained from male homosexual participants in the Multicenter AIDS Cohort Study (MACS). In seroconverters, ADCC-inducing HIV-specific antibodies were detected at the time that the ELISA antibody test was first positive. Within several months, serum ADCC activity stabilized in each individual. In 29 HIV-seroprevalent individuals (HIV seropositive on their first visit), serum ADCC activity remained constant regardless of whether the individual's HIV disease was stable (high stable CD4;n=9) or rapidly deteriorating (sharply declining CD4,n=10; AIDS progressors,n=10). With respect to effector-cell activity, PBMC from HIV-infected individuals with or without AIDS were capable of mediating ADCC with heterologous and usually with autologous sera. Although the level of NK cytotoxic activity and the level of antibody-armed effector cell activity have been reported to decline as disease progresses, our results support previous observations that ADCC effector-cell activity against antibody-coated targets does not decline in HIV infection. These results indicate that both serum and effector cells with ADCC activity are present in HIV-infected individuals shortly after seroconversion and are maintained throughout HIV disease. Although levels of serum and effector-cell ADCC activity do not predict whether an individual will develop AIDS, CD4 cells which express HIV antigens (either produced endogenously or adsorbed onto the surface) could serve as targets for anti-HIV-mediated ADCCin vivo. ADCC could, thereby, contribute to CD4 T-cell depletion in infected individuals. However, since serum and effector-cell ADCC levels do not seem to relate to disease stage or progression, the protective or pathogenic role that ADCC plays in HIV-disease remains unresolved.     

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.     

Pulmonary aspergillosis in the acquired immunodeficiency syndrome

BACKGROUND AND METHODS. Symptomatic pulmonary aspergillosis has rarely been reported in patients with the acquired immunodeficiency syndrome (AIDS). We describe the predisposing factors, the clinical and radiologic features, and the therapeutic outcomes in 13 patients with pulmonary aspergillosis, all of whom had human immunodeficiency virus (HIV) infection and 12 of whom had AIDS. RESULTS. Pulmonary aspergillosis was detected a median of 25 months after the diagnosis of AIDS, usually following corticosteroid use, neutropenia, pneumonia due to other pathogens, marijuana smoking, or the use of broad-spectrum antibiotics. Two major patterns of disease were observed: invasive aspergillosis (in 10 patients) and obstructing bronchial aspergillosis (in 3). Cough and fever, the most common symptoms, tended to be insidious in onset in patients with invasive disease (median duration, 1.3 months before diagnosis). Breathlessness, cough, and chest pain predominated in the three patients with obstructing bronchial aspergillosis, who coughed up fungal casts. Radiologic patterns included upper-lobe cavitary disease (sometimes mistaken for tuberculosis), nodules, pleural-based lesions, and diffuse infiltrates, usually of the lower lobe. Transbronchial biopsies were usually negative, but positive cultures were obtained from bronchoalveolar-lavage fluid or percutaneous aspirates. Dissemination to other organs occurred in at least two patients, and direct invasion of extrapulmonary sites was seen in two others. The results of treatment with amphotericin B, itraconazole, or both were variable. Ten of the patients died a median of 3 months after the diagnosis (range, 0 to 12 months). CONCLUSIONS. Pulmonary aspergillosis is a possible late complication of AIDS; if diagnosed early, it may be treated successfully.