Daily cannabis and reduced risk of steatosis in human immunodeficiency virus and hepatitis C virus-co-infected patients (ANRS CO13-HEPAVIH).

Liver steatosis is common in human immunodeficiency virus (HIV)-hepatitis C virus (HCV)-co-infected patients. Some recent studies have found that cannabis use is negatively associated with insulin resistance in the general population and in HIV-HCV-co-infected patients. Given the causal link between insulin resistance and steatosis, we hypothesized that cannabis use has a positive impact on steatosis. Therefore, we aimed to study whether cannabis use in this population was associated with a reduced risk of steatosis, measured by ultrasound examination. ANRS CO13-HEPAVIH is a French nationwide multicentre cohort of HIV-HCV-co-infected patients. Medical and socio-behavioural data from clinical follow-up visits and annual self-administered questionnaires were prospectively collected. A cross-sectional analysis was conducted using data from the first visit where both ultrasound examination data for steatosis (positive or negative diagnosis) and data on cannabis use were available. A logistic regression model was used to evaluate the association between cannabis use and steatosis. Among study sample patients (n = 838), 40.1% had steatosis. Fourteen per cent reported daily cannabis use, 11.7% regular use and 74.7% no use or occasional use ("never or sometimes"). Daily cannabis use was independently associated with a reduced prevalence of steatosis (adjusted odds ratio [95% CI] = 0.64 [0.42;0.99]; P = .046), after adjusting for body mass index, hazardous alcohol consumption and current or lifetime use of lamivudine/zidovudine. Daily cannabis use may be a protective factor against steatosis in HIV-HCV-co-infected patients. These findings confirm the need for a clinical evaluation of cannabis-based pharmacotherapies in this population. Eudract.ema.europa.eu number, DGS050367.

Liver-related deaths in HIV-infected patients between 1995 and 2010 in France: the Mortavic 2010 study in collaboration with the Agence Nationale de Recherche sur le SIDA (ANRS) EN 20 Mortalité 2010 survey.

OBJECTIVES: The aim of this study was to describe the proportion of liver-related diseases (LRDs) as a cause of death in HIV-infected patients in France and to compare the results with data from our five previous surveys. METHODS: In 2010, 24 clinical wards prospectively recorded all deaths occurring in around 26 000 HIV-infected patients who were regularly followed up. Results were compared with those of previous cross-sectional surveys conducted since 1995 using the same design. RESULTS: Among 230 reported deaths, 46 (20%) were related to AIDS and 30 (13%) to chronic liver diseases. Eighty per cent of patients who died from LRDs had chronic hepatitis C, 16.7% of them being coinfected with hepatitis B virus (HBV). Among patients who died from an LRD, excessive alcohol consumption was reported in 41%. At death, 80% of patients had undetectable HIV viral load and the median CD4 cell count was 349 cells/µL. The proportion of deaths and the mortality rate attributable to LRDs significantly increased between 1995 and 2005 from 1.5% to 16.7% and from 1.2‰ to 2.0‰, respectively, whereas they tended to decrease in 2010 to 13% and 1.1‰, respectively. Among liver-related causes of death, the proportion represented by hepatocellular carcinoma (HCC) dramatically increased from 5% in 1995 to 40% in 2010 (p = 0.019). CONCLUSIONS: The proportion of LRDs among causes of death in HIV-infected patients seems recently to have reached a plateau after a rapid increase during the decade 1995-2005. LRDs remain a leading cause of death in this population, mainly as a result of hepatitis C virus (HCV) coinfection, HCC representing almost half of liver-related causes of death.

Drug-specific risk of non-tuberculosis opportunistic infections in patients receiving anti-TNF therapy reported to the 3-year prospective French RATIO registry.

BACKGROUND: Anti-tumour necrosis factor (TNF) therapy may be associated with opportunistic infections (OIs). OBJECTIVE: To describe the spectrum of non-tuberculosis OIs associated with anti-TNF therapy and identify their risk factors. METHODS: A 3-year national French registry (RATIO) collected all cases of OI in patients receiving anti-TNF treatment for any indication in France. A case-control study was performed with three controls treated with anti-TNF agents per case, matched for gender and underlying inflammatory disease. RESULTS: 45 cases were collected of non-TB OIs in 43 patients receiving infliximab (n=29), adalimumab (n=10) or etanercept (n=4) for rheumatoid arthritis (n=26), spondyloarthritides (n=3), inflammatory colitis (n=8), psoriasis (n=1) or other conditions (n=5). One-third (33%) of OIs were bacterial (4 listeriosis, 4 nocardiosis, 4 atypical mycobacteriosis, 3 non-typhoid salmonellosis), 40% were viral (8 severe herpes zoster, 3 varicella, 3 extensive herpes simplex, 4 disseminated cytomegalovirus infections), 22% were fungal (5 pneumocystosis, 3 invasive aspergillosis, 2 cryptococcosis) and 4% were parasitic (2 leishmaniasis). Ten patients (23%) required admission to the intensive care unit, and four patients (9%) died. Risk factors for OIs were treatment with infliximab (OR=17.6 (95% CI 4.3 - 72.9); p<0.0001)or adalimumab (OR=10.0 (2.3 to 44.4); p=0.002) versus etanercept, and oral steroid use >10 mg/day or intravenous boluses during the previous year (OR=6.3 (2.0 to 20.0); p=0.002). CONCLUSION: Various and severe OIs, especially those with intracellular micro-organisms, may develop in patients receiving anti-TNF treatment. Monoclonal anti-TNF antibody rather than soluble TNF receptor therapy and steroid use >10 mg/day are independently associated with OI.

Liver-related deaths in HIV-infected patients between 1995 and 2005 in the French GERMIVIC Joint Study Group Network (Mortavic 2005 study in collaboration with the Mortalité 2005 survey, ANRS EN19).

BACKGROUND: More than 10 years after the introduction of combination antiretroviral therapy (cART), we examined the trend in the proportion of deaths caused by end-stage liver disease (ESLD) in HIV-infected adults in France between 1995 and 2005. DESIGN AND METHODS: In 2005, 34 departments prospectively recorded all deaths in HIV-infected patients who were followed in those departments (around 24 000). RESULTS: were compared with those of four previous cross-sectional surveys conducted since 1995 using the same methodology. Results Among 287 reported deaths in 2005, 100 (35%) were related to AIDS, and 48 (17%) to ESLD. Three out of four patients who died from ESLD-related causes had chronic hepatitis C. Excessive alcohol consumption was reported in approximately half of the patients (48%). At death, 62% of patients had undetectable HIV viral load and the median CD4 count was 237 cells/microL. From 1995 to 2005, the proportion of deaths caused by ESLD increased from 2 to 17% (P<0.001). The proportion of deaths caused by hepatocellular carcinoma increased from 5% in 1995 to 25% in 2005 (P=0.0337). CONCLUSIONS: Over the 10 years from 1995 to 2005, the proportion of deaths caused by hepatitis C virus-related ESLD has increased in HIV-infected patients. ESLD is currently a leading cause of death in this population, with hepatocellular carcinoma representing a quarter of liver-related deaths. Recommendations for the detection of hepatocellular carcinoma should be strictly applied in these patients.

Opportunistic infections in patients with inflammatory bowel disease: prevention and diagnosis.

Because of the increasing use of immunosuppressive and biological drugs, the occurrence of opportunistic infections has become a key safety issue for patients with inflammatory bowel disease (IBD). Consequently, improvement of healthcare workers' knowledge of this domain is urgent. In this review, the preventive measures that would help to reduce the rate of opportunistic infections in patients with IBD are listed, and the management of situations frequently confronting doctors is considered. In the absence of national and international recommendations, the information given here should help doctors to optimise patient outcomes.

[Antiviral immunization of immunocompromised adults, literature review]. / Vaccination antivirale des adultes immunodéprimés, revue de la littérature.

PURPOSE: Immunization, by preventing infections, has a major interest for the immunocompromised subjects. The aim of this article is to make a point on data concerning efficacy (in terms of immunogenicity) and safety of viral vaccines available in France and to synthesize existing guidelines for four groups of patients: solid organ and hematopoietic stem cell transplant recipients, HIV infected persons and patients treated by immunosuppressive drugs for a systemic disease. CURRENT KNOWLEDGE AND KEY POINTS: Available data about vaccines immunogenicity and safety for immunocompromised adults are rare. However, those data indicate that, when immunization contraindications and recommendations are applied, vaccines remain well tolerated and most of the time immunogenic, even if the percentage of responders is lower compared to non immunocompromised persons. Still, the specific guidelines that have been elaborated for immunization of immunocompromised adults are imprecise and incomplete, emphasizing a lack of data about this topic. FUTURE PROSPECTS: Clinical studies remain necessary to precise vaccines immunogenicity and safety for immunocompromised adults. In the meantime, a harmonization of immunization practices for immunocompromised adults should be proposed, so as to help practitioners to succeed a better immunization coverage for these patients.

[Surveillance of operative site infections in an orthopedic and traumatology surgery department: an example of methodology]. / Proposition d'un protocole de suivi des infections avérées de site opératoire en chirurgie orthopédique et traumatologique.

PURPOSE OF THE STUDY: A program for the prevention of nosocomial infections, including operative site infections (OSI) is a legal obligation in France. According to the CDC, in orthopedic surgery, nosocomial infection is defined as any infection occurring within 30 days of operation, or within one year in the event of material implantation. No surveillance system has been validated and the rate of OSI is unknown in orthopedic surgery. We report the number of OSI observed during a three year period in our unit and describe the characteristic features. MATERIAL AND METHODS: Data were collected from the bacteriology reports on operative site samples with a positive culture. A group of specialists determined the infective nature of the germ and the nosocomial nature of the OSI. Clinical and bacteriological data were noted on a standard datasheet used for prospective follow-up of the number of cases and data processing. During a three-year period (2000, 2001, 2002), among 9397 orthopedic and traumatology operations performed, 86 OSI were identified. Mean patient age was 58 years and mean body mass index was 25.7. The ASA score was >or=II for 72% of patients. RESULTS: The OSI involved an arthroplasty in 23 cases, a traumatology procedure in 21, and tumor treatment in 24. The diagnosis was established within 30 days of operation for 75% and after discharge from hospital in 65.4%. Single-germ infections predominated (n=59). Staphylococcus aureus was isolated in 80.23% of infections. For tumor surgery, the statistically more frequent multiple-germ infections associated coagulase negative Staphylococcus and Gram-negative bacilli. There were six OSI-related deaths. DISCUSSION: Two criticisms can be formulated concerning our surveillance system. First, infections with no identified germ could be missed. The frequency of such infections has been estimated at 2.8 to 19% by different authors. Although patients are automatically recalled for consultation, we were unable to determine the number of patients lost to follow-up at one year. It was thus not possible to determine a precise rate of OSI. Data in the literature have not demonstrated any system providing an exhaustive surveillance, particularly because of the long postoperative period after material implantation. Excepting tumor surgery, Staphylococcus aureus infections predominated. Factors of risk of OSI include the patient's general status, particularly for arthroplasty. We had a mortality rate of 7% for our OSI, corroborating earlier studies and illustrating the severity of such infections. CONCLUSION: Surveillance of OSI in orthopedic surgery requires the development of a system responding to the problem of a long observation period. It would be important to know the precise number of OSI and their characteristic features in order to develop comparison tools.

Emergence of Legionella pneumophila pneumonia in patients receiving tumor necrosis factor-alpha antagonists.

BACKGROUND: Patients treated with tumor necrosis factor-alpha (TNF-alpha) antagonists have an increased risk of infection, but infection due to Legionella pneumophila has rarely been described in patients receiving such therapy. METHODS: A registry involving 486 clinical departments in France was designed by a multidisciplinary group (Recherche Axée sur la Tolérance des Biothérapies [RATIO]) to collect data on opportunistic and severe infections occurring in patients treated with TNF-alpha antagonists. All cases are reported to RATIO in accordance with national health authorities and validated by infectious disease experts. The legionellosis rate among patients treated with TNF-alpha antagonists was compared with the rate in France overall. RESULTS: We report a 1-year consecutive series of 10 cases of L. pneumophila pneumonia in France in 2004, including 6 cases treated with adalimumab, 2 treated with etanercept, and 2 treated with infliximab. The median patient age was 51 years (range, 40-69 years). Eight patients were treated for rheumatoid arthritis, 1 was treated for cutaneous psoriasis, and 1 was treated for pyoderma gangrenosum. The median duration of TNF-alpha antagonist treatment at onset of infection was 38.5 weeks (range, 3-73 weeks). Eight patients were receiving concomitant treatment with corticosteroids, and 6 were receiving treatment with methotrexate. The relative risk of legionellosis when receiving treatment with a TNF-alpha antagonist, compared with the relative risk in France overall, was estimated to be between 16.5 and 21.0. We also report a second episode of confirmed legionellosis following the reintroduction of infliximab therapy. CONCLUSIONS: L. pneumophila pneumonia is a potentially severe but curable infection that might complicate anti-TNF-alpha therapy. In patients receiving anti-TNF-alpha who develop pneumonia, legionellosis should be systematically investigated, and first-line antibiotic therapy should be efficient against L. pneumophila.

[Management of cirrhosis complications in HIV patients coinfected with hepatitis B or C virus]. / Prise en charge des complications de la cirrhose chez les patients VIH co-infectés par une hépatite virale B ou C.

Cirrhosis is a serious complication of viral hepatitis, and its incidence is increasing in HIV patients coinfected with HCV or HBV as they live longer, thanks to effective antiretroviral treatment (Haart). HIV coinfection accelerates the progression of fibrosis in hepatitis. To implement preventive measures, prompt diagnosis of cirrhosis is important, either by liver biopsy or the noninvasive tests for fibrosis now under wide study (FibroTest, FibroScan, etc.). Afterwards, assessment of the severity of cirrhosis and screening for complications are both necessary: testing for liver failure (Child-Pugh and MELD scores), portal hypertension (upper gastrointestinal endoscopy), and hepatocellular carcinoma (ultrasound and alpha fetoprotein assay). Careful consideration of drug prescriptions and possible interactions is essential. Specific treatment for hepatitis B or C virus is possible at this stage of cirrhosis, although more difficult, especially for HCV (results influenced by genotype, additional risk of complications by lactic acidosis or hepatic decompensation). Management of the complications of portal hypertension must be planned, as for those without HIV infection. Treatment of hepatocellular carcinoma is still disappointing, and liver transplantation, although possible in these patients, must be evaluated.

Changes in AIDS-related lymphoma since the era of highly active antiretroviral therapy.

HIV infection is associated with a high incidence of AIDS-related lymphomas (ARLs). Since the use of highly active antiretroviral therapy (HAART), the incidence of AIDS-defining illnesses has decreased, leading to a significant improvement in survival of HIV-infected patients. The consequences of HAART use on ARL are under debate. This study compared the incidence and the characteristics of ARL before and after the use of HAART in a large population of HIV-infected patients in the French Hospital Database on HIV (FHDH) and particularly in 3 centers including 145 patients with proven lymphoma. Within the FHDH, the incidence of systemic ARL has decreased between 1993-1994 and 1997-1998, from 86.0 per 10 000 to 42.9 per 10 000 person-years (P < 10(-30)). The incidence of primary brain lymphoma has also fallen dramatically between the periods, from 27.8 per 10 000 to 9.7 per 10 000 person-years (P < 10(-11)). The analysis of 145 cases of ARL in 3 hospitals showed that known HIV history was longer in the second period than in the first period among patients with systemic ARL (98 versus 75 months; P <.01). Patients had a higher number of CD4 cells at diagnosis during the second period (191 versus 63/microL, P = 10(-3)). Survival of patients with systemic ARL also increased between the periods (from 6 to 20 months; P =.004). Therefore, the profile of ARL has changed since the era of HAART, with a lower incidence of systemic and brain ARL. The prognosis of systemic ARL has improved.

Safety and immunogenicity of a live recombinant canarypox virus expressing HIV type 1 gp120 MN MN tm/gag/protease LAI (ALVAC-HIV, vCP205) followed by a p24E-V3 MN synthetic peptide (CLTB-36) administered in healthy volunteers at low risk for HIV infection. AGIS Group and L'Agence Nationale de Recherches sur Le Sida.

A live recombinant canarypox vector expressing HIV-1 gpl20 MN tm/gag/protease LAI (ALVAC-HIV, vCP205) alone or boosted by a p24E-V3 MN synthetic peptide (CLTB-36) was tested in healthy volunteers at low risk for HIV infection for their safety and immunogenicity. Both antigens were well tolerated. ALVAC-HIV (vCP205) induced low levels of neutralizing antibodies against HIV-1 MN in 33% of the volunteers. None of them had detectable neutralizing antibodies against a nonsyncytium-inducing HIV-1 clade B primary isolate (Bx08). After the fourth injection of vCP205, CTL activity was detected in 33% of the volunteers and was directed against Env, Gag, and Pol. This activity was mediated by both CD4+ and CD8+ lymphocytes. On the other hand, the CLTB-36 peptide was poorly immunogenic and induced no neutralizing antibodies or CTLs. Although the ALVAC-HIV (vCP205) and CLTB-36 prime-boost regimen was not optimal, further studies with ALVAC-HIV (vCP205) are warranted because of its clear induction of a cellular immune response and utility as a priming agent for other subunit antigens such as envelope glycoproteins, pseudoparticles, or new peptides.

Development and standardization of methods to evaluate the antibody response to an HIV-1 candidate vaccine in secretions and sera of seronegative vaccine recipients.

Enzyme-linked immunosorbent assays (ELISA) were developed to test, in serum and mucosal samples, total IgG, total IgA, serum albumin, and anti-gp120 MN and anti-p24 LAI IgG and IgA levels. These ELISAs were optimized according to reagents and experimental conditions. Inter- and intra-assay coefficients of variation ranged from 3.3% to 18.6%. The ELISA results were linear and precise, and for anti-HIV-1 IgG and IgA, the analytical recovery was close to 100%. For IgG and IgA titration against gp120 MN and p24 LAI, standards were made using pooled sera or gammaglobulins with assigned titres in ELISA units per ml (EU/ml). These standards were used to obtain a linear regression curve that could then be used to obtain the titres of experimental samples. The cut-offs for positivity were determined for sera and mucosal fluid using healthy controls. Validation conditions were defined for ELISAs, and samples that did not satisfy these conditions were retested. Measurement of total IgG and IgA allowed normalization and comparison of the results of specific immunoglobulin levels between different samples. Serum albumin was tested as a marker of transudation from serum to mucosal fluid, allowing calculation of the relative coefficient of excretion, which is one element required to determine the origin of the immunoglobulin detected in mucosal samples. These ELISAs were developed with samples from HIV-1-infected and healthy subjects. We now have the tools to study and understand mucosal immunity in seronegative subjects vaccinated with an HIV-1 candidate vaccine.

Muscular bacillary angiomatosis in AIDS.

We describe an unusual case of bacillary angiomatosis first misdiagnosed as Kaposi's sarcoma in muscle in a patient with HIV infection.

[Acyclovir-resistance zona in a immunocompromised HIV seronegative patient]. / Zona résistant à l'aciclovir chez un malade immunodéprimé non infecté par le VIH.

INTRODUCTION: Resistance to antiviral therapy is getting actually more frequent. Immunocompromised host are more concerned with this problem. OBSERVATION: We present a case of disseminated zoster resisting to acyclovir (ACV) therapy, but healing with foscarnet in a man treated with chemotherapy for lymphoma and seronegative for HIV. CI50 of VZV strain was 48 microM for ACV, which was 2.8 times higher than value of the reference OKA strain tested simultaneously, which confirmed the resistance for ACV. DISCUSSION: Immunocompromised patients often present varicella zoster virus (VZV) infection. They usually heal in response to ACV therapy, but some HIV infected patients have already presented with resistant strains of VZV. This case is the first described in a non-HIV infected patient. Foscarnet therapy resulted twice in complete healing because of its direct activity on viral DNA polymerase, so it is efficaceous therapy for patients with thymidine-kinase-deficient ACV-resistant VZV infection.

Safety and immunogenicity of a recombinant HIV type 1 glycoprotein 160 boosted by a V3 synthetic peptide in HIV-negative volunteers.

The safety and the immunogenicity of a recombinant hybrid envelope glycoprotein MN/LAI (rgp160) followed by booster injections of a V3 (MN) linear peptide were evaluated in HIV-negative adults at low risk for HIV infection. Volunteers received either rgp160 in alum at 0, 1, and 6 months (group A), rgp160 at 0 and 1 months followed by V3 at 3 and 6 months formulated in alum (group B), or in Freund's incomplete adjuvant (FIA) (group C). Local and systemic reactions were mild to moderate and resolved within the first 72 hr after immunization. No significant biological changes (routine tests and autoantibodies) were observed. One month after the last injection in either group, neutralizing antibodies (NAs) against the HIV-1 MN isolate were detected in 4 of 5 (A), 7 of 10 (B), and 10 of 10 (C) subjects with significantly higher geometric mean titers in the latter group. Four of nine sera with the highest NA titers against MN weakly cross-neutralized the HIV-1 SF2 isolate; none had NA against the HIV-1 LAI strain or against a North American primary isolate. Specific lymphocyte T cell proliferation to rgp160 was detected in 92% of the subjects after the second injection of rgp160 and in 80% of them 12 months after the first injection. A weak and short-lived envelope-specific CD(4+)-mediated cytotoxic lymphocyte activity was detected at certain time points in few subjects. This prime-boost vaccine approach using rgp160 followed by a V3 peptide was safe in humans, and was able to elicit high levels of neutralizing antibodies and a strong and persistent T cell lymphoproliferative response to rgp160 and to V3. However, the neutralization response was restricted to the homologous HIV-1 strain and little env-specific cytotoxic activity was induced.

Pyogenic and tuberculous spondylodiskitis (vertebral osteomyelitis) in 80 adult patients.

Bacterial spondylodiskitis--i.e., adjacent vertebral osteomyelitis and diskitis--was studied in 80 adult patients. The infection was due to Mycobacterium tuberculosis in 31 cases (39%) and to pyogenic bacteria in 49 cases (61%). The latter pathogens included gram-negative bacilli in 16 cases (20%), Staphylococcus species in 15 (19%), Streptococcus species in 9 (11%), and Corynebacterium species in 1 (1%); the pathogens in the 8 remaining cases (10%) were not identified. Of the patients with tuberculous spondylodiskitis, 55% came from countries where tuberculosis is endemic (P < .001). Cases due to staphylococci and those due to M. tuberculosis were associated with a high frequency of previous active infection with those respective organisms at any site (47% and 42%, respectively; P < .001) and with a high rate of neurological complications (33% and 32%, respectively; P < .001). Nine patients with pyogenic spondylodiskitis (18%) but only one patient with tuberculous spondylodiskitis (3%) had diabetes mellitus (P < .05). Blood cultures were positive in 23 (56%) of the 41 cases of pyogenic spondylodiskitis due to an identified bacterium. Discovertebral needle biopsy contributed to the bacteriologic diagnosis in 29 (74%) of 39 cases.

Invasive aspergillosis in patients with acquired immunodeficiency syndrome: report of 33 cases. French Cooperative Study Group on Aspergillosis in AIDS.

PURPOSE: Acquired immunodeficiency syndrome (AIDS)-associated invasive aspergillosis (IA) is a rare condition, which is mainly reported as isolated cases either antemortem or at autopsy. The role of AIDS itself is controversial, because many of the reported patients exhibited the classic risk factors such as neutropenia and steroid therapy. The aims of this study were to report 33 patients with IA during AIDS and their outcome, focusing on the risk factors and the value of diagnostic procedures. PATIENTS AND METHODS: Thirty-three patients from 17 different medical centers in France were retrospectively included in the study. For pulmonary IA, we defined two types of patients: those with "confirmed IA," describing all the patients with histologically proven disease, and those with "probable IA," who had the development of a new pulmonary infiltrate on chest radiograph and a positive bronchoalveolar lavage (BAL) fluid culture for Aspergillus species without identification of other pathogens. For extrapulmonary IA, the diagnostic criteria included both positive histology and culture. RESULTS: Of the 33 cases included in this series, 91% were recorded during the last 3 years (1989 to 1991), suggesting that aspergillosis is an emerging complication in AIDS. Approximately 50% of the patients did not exhibit any classic risk factor, i.e., neutropenia and steroid treatment; almost all patients had a CD4 cell count less than 50/mm3. The mycologic culture from BAL was the method of choice for the diagnosis of invasive pulmonary disease because it was known to correlate well with histologic findings obtained either antemortem or postmortem. Of 28 patients with a positive BAL culture for Aspergillus, 15 underwent a biopsy or autopsy and 14 were positive at histology. Serum antigen detection was positive in only 4 of 16 tested patients. Clinical and radiologic signs did not differ from those observed in neutropenic patients without human immunodeficiency virus, except for the higher incidence of neurologic complications in AIDS. Interestingly, we observed three cases of invasive necrotizing tracheobronchial aspergillosis with acute dyspnea and wheezing. The use of amphotericin B (0.5 mg/kg/d) and/or itraconazole (200 to 600 mg/d) was most often unsuccessful. Only four patients experienced clinical and radiologic improvement. The mean interval between the diagnosis of IA and death was 8 weeks (range: 3 days to 13 months). CONCLUSIONS: This study suggests that aspergillosis is an important life-threatening condition in the advanced stage of AIDS. It requires an early diagnosis with BAL fluid culture and careful therapeutic evaluation.