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Randomized, open-label, prospective clinical trial assessing efficacy and safety on hyperlipidemia of a switching from a regimen including one protease inhibitor and one thymidine analogue to atazanavir/ritonavir plus abacavir/lamivudine or tenofovir/emtricitabine. Adult HIV-infected patients on their first antiretroviral therapy (of at least 48-week duration), including one protease inhibitor and zidovudine or stavudine, with stable immunovirologic features, and having diagnosis of persisting hyperlipidemia, were randomized to replace current treatment with atazanavir/ritonavir plus abacavir/lamivudine (arm A) or tenofovir/emtricitabine (arm B), and were followed for 48 weeks. Eighty-nine patients were enrolled: 42 patients were randomized to arm A, and 47 to arm B. At the end of the 48-week follow-up, incidence of virologic failure was comparable in both arms, and associated with a poor drug compliance. Increase in CD4 lymphocyte count was significantly higher in arm A after a 24-week study period (62.5 versus 39.2 x 10(6) cells/L; p < 0.05), while immunologic responses were comparable at the end of 48-week follow-up (91.5 versus 83.6; p > 0.05). A statistically significant reduction (-15.4%) in mean triglyceridaemia versus respective baseline values was reported in both groups (p < 0.05), without statistically significant difference between arm A and B. Similar results were reported for total cholesterol and low-density lipoprotein (LDL) cholesterol levels. Safety and tolerability profiles were comparable in both groups. Switching from a protease inhibitor- and thymidine analogue-based antiretroviral regimen to atazanavir/ritonavir plus abacavir/lamivudine or tenofovir/emtricitabine proved effective in the management of hyperlipidemia, without significant differences in lipid-lowering effect, virologic efficacy, and safety profile between these regimens.

Recent data indicate that fosamprenavir/ritonavir as part of an initial antiretroviral regimen in HIV-1 -infected patients is associated with favourable efficacy and tolerability and in the KLEAN study (kaletra versus lexiva with epivir and abacavir in antiretroviral-naive patients) it was found to be non-inferior to lopinavir/ritonavir in association with abacavir/lamivudine. In our open-label, observational study conducted in 82 therapy-naíve HIV-1-infected patients followed-up for 18 months, virological and immunological efficacy was comparable in subjects receiving a fosamprenavir/ritonavir-based and a lopinavir/ritonavir-based treatment (proportions of patients with HIV RNA

Five out of nine consecutive patients with HIV-related visceral aspergillosis observed by us since 1984 were diagnosed only at necropsy examination. The histopathological features of these five patients [two with isolated pneumonia, one with central nervous system (CNS) involvement, one with brain abscess and respiratory disease and one with pulmonary, pleural and kidney infection] have been evaluated according to epidemiological, clinical and radiological features. On the basis of our experience, life-threatening aspergillosis, which is often misdiagnosed or missed in the setting of HIV infection and AIDS, should be suspected in patients with far-advanced underlying disease and unexplained signs and symptoms, even in the absence of some presumed risk factors (i.e. neutropenia and prior steroid treatment). Plain chest radiography and bronchoscopy with broncholaveolar lavage may fail to reveal respiratory disease, CNS aspergillosis is not necessarily associated with suggestive neuroradiological features and disseminated disease may present with multiorgan failure. The unfavorable outcome of this emerging AIDS complication can be improved only by earlier diagnosis based on invasive techniques and appropriate and timely treatment.

A rare case report of serious, relapsing, and difficult-to-treat Strongyloides stercoralis enteric infestation that occurred in a patient affected by the autoimmune Sjögren disease (a pathologic association never reported before), chronically treated with corticosteroids, has been presented and evaluated on the ground of the available literature evidences in this field. In particular, the role of underlying (and iatrogenic) immunodeficiency in the pathogenesis of S. stercoralis persisting infection and the unresolved diagnostic and therapeutic issues in the setting of strongyloidiasis are discussed. Particular attention is focused on the need to maintain clinical suspicion for this nematode worm infestation in patients suffering from a large spectrum of collagen vascular diseases, and the need for randomized clinical trials to determine suitable first-line and subsequent lines of treatment, especially when immunodeficiency and a relapsing Strongyloides disease are suspected. © 2006 Lippincott Williams & Wilkins, Inc.

Cardiovascular risk factors, including the fat redistribution syndrome, dyslipidaemia, insulin resistance and diabetes mellitus, have been increasingly described in association with new potent protease inhibitor-based antiretroviral therapies in patients with HIV infection. The introduction of highly active antiretroviral therapy (HAART) in clinical practice has altered the natural history of HIV remarkably, leading to a notable extension of life expectancy, and prolonged lipid and glucose metabolism abnormalities are expected to lead to significant effects on the long-term prognosis and outcome of HIV-infected patients. Prediction modelling, surrogate markers and hard cardiovascular end points suggest an increased incidence of cardiovascular diseases in HIV-infected subjects receiving HAART, even though the absolute risk of cardiovascular complications remains low, and must be balanced against the evident virological, immunological and clinical benefits descending from combination antiretroviral therapy....

Infective endocarditis is relatively uncommon in childhood, but its epidemiology has changed in the past three to four decades and its incidence has been increasing in recent years. With the improved survival rates of children with congenital heart diseases and the overall decreased frequency of rheumatic valvular heart disease in developed countries, congenital cardiac abnormalities now represent the predominant underlying condition for infective endocarditis in children over the age of two years in Western Europe and Northern America. Moreover, the complex management of neonatal and pediatric intensive care unit patients has increased the risk of catheter-related endocarditis. More specifically, the surgical correction of congenital heart alterations is associated with the risk of postoperative infections. Endocarditis in children may be difficult to diagnosis and manage. Emerging resistant bacteria, such as methicillin- or vancomycin-resistant staphylococci and vancomycin-resistant enterococci, are becoming a new challenge for conventional antibiotic therapy. Newer antimicrobial compounds recently introduced in clinical practice, such as streptogramins and oxazolidinones, may be effective alternatives in children with endocarditis sustained by Gram-positive cocci resistant to glycopeptides. Home intravenous therapy has become an acceptable approach for stable patients who are at low risk for embolic complications. However, further clinical studies are needed in order to assess efficacy and safety of these antimicrobial agents in children. This review should help outline the most appropriate antimicrobial treatments for infective endocarditis in children.

A unique case of severe, multiple, microbiologically-confirmed pulmonary Mycobacterium avium-intracellulare lesions occurred in a female with decompensated liver cirrhosis, and went to cure after around 2 y despite the impossibility to deliver an effective antimicrobial chemotherapy, owing to the patient's intolerance. From an extensive literature review, we underline a possible mechanism prompting mycobacterial disease during advanced liver disease, while we retrieved only 2 described cases of possible spontaneous resolution of Mycobacterium terrae lung disease, although both were reported in patients without end-organ liver disease, who received a specific combined chemotherapy for an appreciable time period. On the other hand, while decompensated liver cirrhosis is more frequently complicated by a peritoneal localization of bacteria and very infrequently mycobacteria, the reported case represents the first severe pulmonary localization of multiple lesions due to Mycobacterium avium-intracellulare. Moreover, this extraordinary episode resolved spontaneously within the 2-y follow-up, as documented by bronchoalveolar lavage, culture, high-resolution CT scans, and scintigraphic examination.

A case report of acute, massive, prolonged hepatitis related to secondary syphilis in a patient with undiagnosed HIV infection is described together with possible pathogenetic mechanisms. This is a rare occurrence in resource-rich countries in the era of antibiotics. The impaired immune response and the dysregulation of the cytokine network may have played a role in mediating this severe expression of HIV-associated secondary syphilis. An apparently unexplained acute hepatitis should deserve accurate screening for sexually transmitted diseases, including syphilis and HIV infection.

The first described case of acute concurrent hepatitis and meningitis as the isolated mode of presentation of syphilis in an HIV-infected homosexual man undergoing antiretroviral therapy is presented and discussed, on the ground of literature evidences and relevant epidemiological, diagnostic, therapeutic, and public health implications. A negligible epidemiological and medical history and the absence of other signs and symptoms of syphilis delayed the diagnosis, which was later confirmed through associated positive serum and cerebrospinal fluid syphilis serology. Histopathologic studies of the liver were also performed, as well as brain computed tomography scan. High-dose intravenous penicillin administration led to a rapid cure of both complications. When facing young patients with some signs and symptoms of hepatic and meningeal involvement, a syphilitic etiology should not be underestimated, especially when concurrent conditions (HIV disease and antiretroviral therapy in our case) may render differential diagnosis even more difficult. The recent resurgence of syphilis also focuses important public health issues, as a sign of a reduced attention to barrier preventive measures against sexually transmitted diseases.

The iatrogenic form of Kaposi's sarcoma (KS) is typically observed among transplant recipients, and the most appropriate therapeutic approach (usually including reduction of immunosuppression, specific chemotherapy, and/or administration of antiviral agents against human herpes virus-8) is still controversial. Available experiences on the effect of the anti-herpes viruses drug cidofovir provide conflicting results. Herein, we report the clinical, histological, and virological features of a liver transplant recipient successfully treated with a combined therapy of cidofovir and liposomal daunorubicin, associated with a reduction of the immunosuppressive regimen, for an advanced cutaneous and visceral KS.

Objective and methods: The aim of our study was to analyse retrospectively the nature and frequency of antiretroviral prescriptions for 990 HIV-infected patients followed at our outpatient centre in Bologna, Italy, from January 2003 to March 2004. The main focus of the study was to identify the most commonly prescribed combinations and their related expenses, in order to identify the most competitive treatment regimens with regard to costs. Prescriptions were given directly to patients at monthly intervals, and drug treatment adherence data was stored in an electronic database. Antiretroviral regimens administered for the longest period to each patient during the 15 months of the study were selected for the study. All patients treated for

A puzzling case report of a septicaemic post-surgical staphylococcal knee arthritis which did not respond to long-term courses of associated rifampicin and teicoplanin or vancomycin, despite apparently favourable in vitro susceptibility assays, but which rapidly resolved after i.v. followed by oral administration of linezolid is presented, and discussed in the context of the most recent literature evidence. The lack of response to a 14-d-long course of glycopeptides does not find explanation from the in vitro minimum inhibitory concentrations (MIC90) of involved organisms, which showed full susceptibility of Staphylococcus aureus to vancomycin and teicoplanin, and sensitivity of an accompanying Staphylococcus epidermidis isolated from blood cultures to vancomycin and rifampicin, with borderline 'intermediate' values found for teicoplanin. Since neither bone involvement nor abscess formation was of concern, effective glycopeptide and rifampicin penetration into infectious tissue should have been assured. From a clinical viewpoint, the introduction of a 2-week i.v. linezolid followed by 1 further week of oral linezolid led to complete clinical and microbiological cure, and an unexpected functional success.

The aim of our survey is to investigate the epidemiology and in vitro antimicrobial susceptibility levels of 35 consecutive Mycobacterium xenopi strains responsible for confirmed disease at a University Hospital from 1993 to 2002 and to identify eventual differences in the in vitro sensitivity profile between the 17 strains isolated from patients with HIV disease and the 18 isolates cultured from non-HIV-infected individuals.The involvement of lower airways accounted for 88.6% of cases; but atypical pulmonary findings, including cavitation and a prominent inflammatory reaction, recently emerged in HIV-infected patients successfully treated with HAART, which raises the possible role of immune reconstitution syndrome in the clinical pathomorphism of this opportunistic disease. When compared with non-HIV-infected patients, patients with HIV disease had a lower mean age and a tendency to suffer from late relapses. The greatest overall in vitro sensitivity rate was registered for capreomycin and protionamide (100% of strains) followed by kanamicin (96.6%), whereas susceptibility rates for the first-line compounds such as ethambutol, isoniazid, and rifampicin were slightly lower (85.7% to 91.4%). No temporal variation in the susceptibility index was seen over the study decade. Non-HIV-infected patients experienced a higher frequency of M. xenopi isolates that proved to be resistant to at least one tested compound compared with HIV-associated episodes, despite the heavy and prolonged exposure of HIV-infected patients to broad spectrum antimicrobials, which included agents effective on atypical mycobacteria. Only one HIV-positive patient developed rifampicin resistance in his third disease recurrence.A rapid diagnosis, a reliable differentiation between colonization and disease, and an optimal therapeutic choice for atypical mycobacterial disease (including M. xenopi one) are still serious challenges for clinicians and bacteriologists who treat immunocompromised patients, such as those with HIV disease. In the immunocompromised host, diagnostic difficulties posed by late identification and eventually concurrent opportunistic disorders add their negative effects to therapeutic problems due to the unpredictable in vitro susceptibility profile of atypical mycobacteria, such as M. xenopi.

Although being a rare occurrence, brain cryptococcoma may represent an emerging issue, because of its relationship with a broadening range of risk factors, including malignancies, neutropenia, end-organ failure, bone marrow and solid-organ transplantation, and multiple underlying causes of primary-secondary immunodeficiency. A cerebral cryptococcoma in a chronic nephropathic HIV-negative subject with homocystinuria, completely cured with neurosurgery and voriconazole after fluconazole failure, is described.

BACKGROUND: Autoimmune hepatitis (AIH) has three different presentations: chronic, acute and asymptomatic. Aim: To evaluate AIH presentation in Italian patients and investigate criteria that differentiate between acute-type AIH and acute viral hepatitis. DESIGN: Prospective observational study. METHODS: Eighty-six consecutive patients with type 1 AIH and 41 with acute viral hepatitis (controls) were studied. 'Acute' AIH was defined as recent-onset (

Leishmaniasis is emerging as a common and serious opportunistic disease for patients with HIV infection. Almost all cases of HIV-Leishmania coinfection have been described in Mediterranean countries and they occur with various clinical presentations, ranging from typical visceral forms to asymptomatic or atypical cases, including cutaneous and mucocutaneous leishmaniasis. Pentavalent antimony compounds have been the mainstays of antileishmanial therapy for half a century and new lipid formulations of amphotericin B seem reliable, but the most effective treatment remains unknown. We describe a patient who was HIV infected and an intravenous drug user, with an unusual disseminated cutaneous leishmaniasis, after an initial visceral disease and after a 13-month maintenance treatment with liposomal amphotericin. The severe concurrent immunosuppression probably played an essential role in leading to this atypical cutaneous form, characterized by diffuse, nonulcerated, nonscabby maculopapular lesions.

Objective and Methods. – A four-year retrospective survey was carried out in our Infectious Disease ward, to point out discrepancies between immediately hospitalized patients, and those referred to us for admission, but needing transferal elsewhere, due to lack of a suitable hospital room. Results. – Since the year 2000, 439 patients out of 1,979 needing hospitalization (28.5%), could not be admitted to our ward. After increasing the number of rooms in our Ward (June 2002,16 to 35 beds), the described phenomenon decreased sharply, but a subsequent stabilization followed until July 2003, with around 13% of Infectious Disease patients sent elsewhere for hospitalization,. Patients with severe, transmissible diseases were of particular concern, when the accepting Infectious Disease unit is located 40-120 Km far from our city. This was the case for nearly 25% of patients refused by our Hospital, since the year 2000. Conclusions. – Infectious Disease wards need a continuous fitting to economic, technical, human, and professional health care resources, on the ground of ever-changing predominant diseases and/or problems. A strict monitoring of hospital admission needs in the Infectious Disease setting is strongly needed, to improve care of managed patients in the Bologna metropolitan area in the future.

Due to shared risk factors for transmission, coinfection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) is a very common event. The prevalence of HCV infection among HIV-positive patients averages about 35% in the United States and Europe, but in clinical populations where there is a great prevalence of intravenous drug use as a risk factor for acquiring HIV, this value may be as high as 80-90%. Several studies have confirmed that HIV coinfection accelerates the natural course of chronic hepatitis C and an increased risk of liver cirrhosis, hepatocellular carcinoma, and decompensated liver disease has been found in coinfected subjects. Other studies have shown an increased risk of progression to acquired immunodeficiency syndrome (AIDS) and AIDS-related death among HIV-HCV-positive persons, suggesting that HCV coinfection may accelerate the course of HIV disease. In addition, hepatitis C may affect the management of HIV infection, increasing the incidence of liver toxicity associated with the antiretroviral regimens. The optimal therapeutic approach to HCV infection in HIV coinfected patients is still uncertain, because of the complex pathogenesis of both infections, potential drugdrug interactions, and the poor literature and information available about safety and efficacy of an interferon (IFN) and ribavirin combination in this clinical population. Available data show that the sustained virological response rates in coinfected persons treated with standard IFN plus ribavirin range from 18-40%, and several studies with pegylated IFN plus ribavirin are ongoing.

Objective: To investigate the impact of 215 HIV-1 revertants on the risk of virological failure of the first thymidine analog-containing highly active antiretroviral therapy (HAART).Design: The study included 491 HIV-1 subjects of the Italian Cohort Naive for Anti retrovirals, 405 of whom received a genotypic assay before therapy and had a virological follow-up.Methods: Pre-treatment genotypic resistance was assessed by sequencing of the whole protease (PR) and reverse transcriptase (RT) region.Results: Three (3.2%) and 13 (3.3%) individuals with recent (n = 95) and chronic (n = 396) HIV-1 infection carried an HIV-1 strain with 215 revertants (215D/C/E/A/V), respectively. In contrast, nucleoside associated mutations were higher in the former (15.8%) compared with the latter group (6.8%) (P = 0.005). A multivariable regression model, considering pre-HAART viral load levels, use of saquinavir-hard gel as the only PI, use of zidovudine, number of other RT and PR mutations, indicated that patients carrying 215 revertants had an increased risk of virological failure compared with those not carrying such mutants (adjusted relative hazard = 2.97 95% confidence interval, 1.11-7.94, P = 0.03). Among patients with 215 revertants, who experienced virological failure, four out of seven showed the emergence of the 215Y resistant mutation. The probability of 215Y occurrence was different between patients carrying 215 revertants compared with those who did not carried these mutants (P = 0.006).Conclusions: HIV-1 215 revertants with an increased ability for selecting 215Y mutation are associated with a higher risk of virological failure and may lead to the appearance of virus carrying 215Y/F mutation in vivo. These findings suggest that 215 revertant viruses may compromise the efficacy of the first thymidine analog-containing regimen. (C) 2004 Lippincott Williams Wilkins.

Objective and methods. – Ten consecutive HIV infected patients were evaluated to assess the relationship among thymic residual tissue, first-line antiretroviral therapy, thymic size evolution, and markers of HIV disease progression. Computerized tomography (CT) study of thymus was performed before starting a triple antiretroviral therapy, and repeated after 12 months, and thymic size was evaluated by a standard score staging. Results. – Initial thymic size tested significantly dependent on patients’ age, while no other variable seemed to affect this feature, but baseline CD4+ lymphocyte count. After a 12-month therapy, a relationship between increased thymus score, and a favourable therapeutic response proved evident. Increase (three cases) or maintenance (four cases) of thymic volume paralleling the treatment-related immune system recovery obtained after 12 months of HAART, may represent the morphological response to an effective therapy. Patients with increase of thymic size experienced a greater 12-month rise of mean CD4+ lymphocyte count compared with baseline levels, opposed to patients maintaining their baseline thymic index. The temporal evolution of both absolute CD8+ cell count and plasma HIV-RNA levels, did not reveal any significant difference compared with baseline levels (patients maintaining a stable thymus volume versus those experiencing an increase of thymus CT score) although a tendency towards a better gain of CD4+ cell count and drop of viremia tested more evident among the patients with an increased thymus score. Conclusion. – Thymopoiesis has a key role in the immune recovery following antiretroviral therapy in adults, and a relationship between morphological and functional activity of thymus is confirmed.

The frequency, the microbiology and clinical features of AIDS-related primary episodes and relapses of cryptococcosis, before and after the introduction of highly active antiretroviral therapy (HAART), were compared. The study covered 58 cases diagnosed before the introduction of HAART, and eight episodes since 1997. Because of negative cultures, we sought a sensitive laboratory assay such as detection of polysaccharide antigen. Despite later diagnosis, there was reduced disease mortality. Clinical suspicion for HIV-associated cryptococcosis should be maintained in immunocompromised subjects. The introduction of HAART has led to significant clinical and laboratory changes of HIV-related cryptococcosis.

Two hundred and twelve HIV-positive patients who started a new protease inhibitor (PI)-based antiretroviral regimen between January 1998 and December 2000 in our tertiary care centre were prospectively followed-up during a 12-month study period, in order to assess the incidence of hyperlipidaemia and related clinical adverse events. At the end of 1-year follow-up, PI-containing antiretroviral treatment led to a statistically significant increase in serum triglyceride levels (P

Although HIV infection is often associated with several rheumatic diseases, the coexistence of this retroviral infection and systemic lupus erythematosus (SLE) is extremely uncommon. Generally, HIV-related immunosuppression improves SLE symptoms, and antiretroviral therapy may lead to an autoimmune disease flare subsequent to the increase of circulating CD4+ cell number. Two HIV-infected female patients with SLE and discoid lupus erythematosus (DLE) diagnosed a few months after the highly active antiretroviral therapy initiation, are described. To our knowledge, this is the second case of DLE and the twenty-seventh case of SLE reported to date in association with HIV infection.

Objectives: the aim of our work is to evaluate the role of statins and fibrates in the management of hyperlipidaemia in HIV-infected patients receiving highly active antiretroviral therapy. Design: Open-label, randomized, prospective study of the efficacy and safety of bezafibrate, gemfibrozil, fenofibrate, pravastatin and fluvastatin as pharmacologic treatment for protease inhibitor-related dyslipidaemia. Methods: Plasma lipid levels of 656 HIV-infected patients who referred to our tertiary care centre and were on protease inhibitor-based antiretroviral therapy for at least 12 months have been evaluated. All patients had HIV viral load < 50 copies/ml and presented with hypertriglyceridaemia of at least 6 months duration that was unresponsive to a hypolipidaemic diet; all have been treated with bezafibrate, gemfibrozil, fenofibrate, pravastatin, or fluvastatin for 12 months. Results: Of the 656 patients observed 113 (17.2%) received pharmacological therapy, while seven patients were excluded from evaluation due to early drop-out. Of the 106 evaluable subjects, bezafibrate was used in 25 cases, gemfibrozil in 22, fenofibrate in 22, pravastatin in 19, and fluvastatin in 18. At the close of 1-year follow-up, fibrates led to a reduction of 40.7% and 21.9% versus baseline triglyceridaemia and cholesterolaemia, respectively (P < 0.001), and statins led to a reduction of 34.8% and 25.2% versus baseline triglyceride and total cholesterol levels, respectively (P

Objective: To determine the turnover for each antiretroviral drugs present in TP’s of patients under care for HIV infection, with a special focus on PI’s and NNRTI’s. Design/Methods: We have carried out a retrospective analysis with the aim of evaluating the turnover of each drug in the 3-year period 1998-2000. Using a specifically designed software, it was possible to determine the changes in TP for each single patient. We then calculated a different weighted percentage for each drug on the basis of the time interval from the drug entry to its exclusion from the TP: the shorter the interval, the greater the assigned weight. Finally we carried out a cluster analysis in order to obtain homogeneous groups of molecules showing the same degree of therapy switches. We established that a higher average score corresponds to a higher therapy switch rate. Results: Zidovudine/Lamivudine combination, Indinavir, Lamivudine, Nerivapine and Nelfinavir are the drugs with the lowest turnover. On the other hand, Saquinavir, Didanosine, Zidavudine, and Stavudine show the highest turnover. Conclusion: The introduction of NNRTI’s with the associated switch from PI’s (Saquinavir, Nelfinavir) and the Zidavudine/Lamivudine combination enables a simplification of the treatment. This practice appeared to be a good choice in the 3-year period under consideration. The adoption of these therapeutic solutions reduce the turnover, consequently giving more stability to TP’s.

An extraordinarily rare case report of mixed fat redistribution syndrome associated with osteopenia but not with relevant metabolic abnormalities is documented in a prepubertal child with congenital HIV infection treated with antiretroviral therapy since the age of six months, up to the present age of 12 years and two months. The possible relationship with prior and present antiretroviral treatment, and with the most recent literature evidences published in both adults and children with HIV disease are discussed, in order to focus these emerging adverse effects of long-term antiretroviral therapy in the paediatric population, and stimulate further investigation in this field.

Objective: To determine the efficacy of efavirenz introduction in first-line HAART compared with salvage multidrug regimens. Patients and methods: Prospective 15 month comparison of 107 consecutive HIV-infected patients starting efavirenz, according to laboratory and clinical outcome of first-line versus rescue drug use, therapeutic history and association of selected antimicrobial agents: naive patients were compared with nucleoside reverse transcriptase inhibitor (NRTI)-experienced patients in the first group, and patients in the second group who had one or more NRTI changed when starting a rescue treatment containing one or more novel protease inhibitors (Pis) were compared with those who did not. Results: Efavirenz was administered with one or more novel NRTIs to 55 patients (27 antiretroviral-naive and 28 patients experienced with NRTIs only), compared with 52 patients who needed a multidrug salvage regimen after two or more failures of a 15-40 month PI-containing regimen. In an intention-to-treat analysis, con-sidering early interruption or an unsatisfactory virological course as a failure, only one patient on salvage therapy completed a favourable 15 month follow-up, compared with 31 patients experiencing first-line efavirenz-based HAART (P < 0.0001). The immunological response was less affected in both intensity and duration in patients undergoing rescue therapy. While no significant outcome difference was detected in the first group between naive and NRTI-experienced patients, among the salvage subjects the change of one or more NRTIs seemed to significantly improve virological and immunological outcome. Viral genotyping detected at least the K103N mutation in 41% of the 78 evaluable patients, despite lack of exposure to efavirenz and related compounds. Salvage patients had a significantly greater frequency of non-nucleoside RTI (NNRTI) resistance compared with the first-line group (P< 0.0001), in proportion to the extent of mutations affecting other drug classes (P < 0.0001). Conclusion: An efavirenz-based initial triple drug HAART proved significantly more effective than efavirenz adjunct to a rescue treatment performed after repeated failures of PI-based regimens. The unsatisfactory response of the salvage group was probably due to diffuse cross-resistance descending from previous therapy, even when NNRTIs were never administered.

Background: Cellulitis and soft tissue infection are underestimated complications of HIV disease. Patients and methods: Sixty-seven bacteriologically proven consecutive episodes were identified among 2221 HIV-infected patients hospitalized in a 10-year period, and assessed according to several epidemiological, microbiological and clinical variables. Results: Staphylococcus aureus was the most frequently cultured pathogen (50% of 92 isolates), followed by Pseudomonas spp., Escherichia coli and Streptococcus pyogenes; a polymicrobial infection was present in 38.1% of episodes. Drug addiction (p

Osteonecrosis has shown an increased incidence in HIV-infected patients during the last few years, and has been looked as a side effect of highly active antiretroviral therapy, possibly related to hyperlipidemia. Five cases of osteonecrosis were observed among over 1300 patients with HIV disease. According to our experience, novel antiretroviral regimens do not represent a constant risk factor for avascular necrosis of bone during HIV infection.

To assess the correlation between antiretroviral treatment and dyslipidaemia in HIV-infected patients, and the role of bezafibrate as a lipid-lowering agent.We retrospectively compared serum lipid levels of five groups of 40 patients, each of them treated with either saquinavir hard gel, indinavir, or ritonavir (associated with two nucleoside analogues), or dual nucleoside reverse transcriptase inhibitors (NRTI) with or without a non-nucleoside reverse transcriptase inhibitor (NNRTI), or not treated with antiretrovirals, randomly selected from nearly 1000 HIV-infected patients followed-up foror= 12 months, while on the relevant therapy. Hypertriglyceridaemia was defined by triglyceride levelsor= 172 mg/dl, and hypercholesterolaemia by cholesterol levelsor= 200 mg/dl. All patients with triglyceridaemia300 mg/dl and cholesterolaemia220 mg/dl for at least 6 months, and unresponsive to aor= 3-month diet, started bezafibrate (400 mg/day), and were prospectively followed-up at aor= 3-month interval, evaluating both efficacy and tolerability of the hypolipidaemic treatment, provided that they did not change their protease inhibitor treatment for reasons other than metabolic abnormalities.Hypertrygliceridaemia occurred in 75 patients out of 200 (37.5%), but was significantly more frequent and severe with ritonavir vs. indinavir (P0.001), and in subjects given indinavir vs. all remaining patients (either treated or not) (P0.001), while isolated saquinavir use was associated with higher tri glyceride levels than NRTI-NNRTI treatment alone, or no antiretroviral therapy (P0.03). Hypercholesterolaemia was found in 27 subjects (13.5%), and a significantly higher frequency and severity was shown in patients treated with indinavir and ritonavir vs. saquinavir, NRTI-NNRTI, and no anti-HIV therapy (P0.05 to P0.001). No appreciable difference was found between patients undergoing NRTI-NNRTI and untreated controls, for all evaluated variables. Bezafibrate was administered once daily for 6-18 months to 49 patients with elevated and diet-resistant hyperlipidaemia due to ritonavir or indinavir (27 and 22 subjects, respectively), and reduced triglyceride and cholesterol levels by 35% and 25%, respectively over 6 months, without differences between the underlying protease inhibitor regimen. Thirty-three patients (67.3%) reached a normal triglyceridaemia after 6-9 months, and normal cholesterol levels were obtained in all subjects. Bezafibrate proved safe and well tolerated.Careful monitoring of the serum lipid profile is needed during antiretroviral therapy, including protease inhibitors, to identify the need for a diet and/or an hypolipidaemic treatment, and to prevent clinical sequelae related to long-term dyslipidaemia. Specific guidelines for the management of disorders of lipid metabolism in HIV-infected patients are needed.

An evaluation was made of the frequency of outcomes, the features, and one-year outcomes of the substitution, carried out because of failure or toxicity, of protease inhibitor (PI)-containing highly active antiretroviral therapy (HAART). Nine hundred and seventy-two HIV-infected patients were prospectively followed up since 1996, with the condition that they had a minimum 80% adherence to prescribed regimens. Four hundred and fifty-two changes occurred in 397 of the 876 evaluable patients (45.3%). Virological and/or immunological failure was of concern in 245 cases (54.2%). Interest in saquinavir had the greatest incidence and earliest occurrence (although the subsequent switch had a significantly better outcome than that of patients failing with other PIs); nelfinavir benefited from a shorter time to change and a worse long-term outcome (probably attributable to its predominant use in indinavir- and ritonavir-experienced patients); while indinavir showed the lowest overall frequency of substitution. Intolerance occurred in the remaining 207 cases (45.8%); with saquinavir being better tolerated than other PIs. A favourable outcome was obtained more frequently when poor tolerability was of concern, compared with therapeutic failure ( P

Clinical charts of 2,398 consecutive HIV-infected patients hospitalized over an 8-year period were reviewed retrospectively to identify all cases of Serratia infection and to evaluate the occurrence and outcome of these cases according to several epidemiological. clinical, and laboratory parameters. Seventeen of 2,398 (0.71%) patients developed Serratia marcescens infections: nine had septicaemia, six had pneumonia, one had a lymph node abscess, and one had cellulitis. All patients were severely immunocompromised, as evidenced by a mean CD4+ lymphocyte count of70 cells/microl and a frequent diagnosis of AIDS (13 patients). When compared with other disease localizations, septicaemia was related to a significantly lower CD4+ cell count and a more frequent occurrence of neutropaenia. Antibiotic, corticosteroid, or cotrimoxazole treatment was frequently carried out during the month preceding disease onset. Hospital-acquired Serratia spp. infection was more frequent than community-acquired infection and was significantly related to AIDS, neutropaenia, and sepsis. Antimicrobial sensitivity testing showed complete resistance to ampicillin and cephalothin but elevated susceptibility to ureidopenicillins, second- and third-generation cephalosporins, aminoglycosides, quinolones, and cotrimoxazole. An appropriate antimicrobial treatment attained clinical and microbiological cure in all cases, in absence of related mortality or relapses. Since only 13 episodes of HIV-associated Serratia spp. infection have been described until now in nine different reports (7 patients with pneumonia, 3 with sepsis, 1 with endophthalmitis, 1 with perifolliculitis, and 1 with cholecystitis), our series represents the largest one dealing with Serratia marcescens infection during HIV disease. Serratia marcescens may be responsible for appreciable morbidity among patients with HIV disease, especially when a low CD4 + cell count, neutropaenia, and hospitalization are present. The clinician and the microbiologist facing a severely immunocompromised HIV-infected patient with a suspected bacterial disease should consider the Serratia spp. organisms. In fact, a rapid diagnosis and an adequate and timely treatment can avoid disease relapses and mortality.

Two hundred and twenty-four episodes of Pseudomonas spp. complications that occurred in 179 consecutive patients with HIV infection were retrospectively reviewed. Pseudomonas spp. organisms were responsible for 11.6% of 1933 episodes of non-mycobacterial bacterial diseases (5.4% of 1072 episodes of sepsis), observed over an 8-year period; 20.7% of patients experienced disease relapses (45 episodes). These complications mostly involved lower airways (66 cases), urinary tract (53 episodes), and blood (34 cases), with Pseudomonas aeruginosa isolated in 161 episodes, and other Pseudomonas spp. in the remaining 63 cases. An advanced HIV disease was frequently present (as expressed by a prior diagnosis of AIDS, a low CD4+ lymphocyte count, and leukopenia–neutropenia). Indwelling intravascular and urinary catheters were often associated with bacteremia and urinary tract involvement, respectively. More than 60% of patients were given antibiotics and/or cotrimoxazole in the month preceding the onset of Pseudomonas spp. disease. Bacterial strains isolated from our HIV-infected patients showed a favorable sensitivity to piperacillin, ceftazidime, imipenem, amikacin, tobramycin, and ciprofloxacin. An adequate antimicrobial treatment led to clinical and microbiological cure in 73.2% of patients at the first episode, and in 22.3% more subjects after one or more relapses. A lethal outcome occurred in only eight patients of 179 (4.5%), suffering from a far advanced HIV disease; P. aeruginosa infection directly contributed to death in four cases (sepsis, and/or pneumonia). Nosocomial disease occurred in 46.4% of the 224 episodes, and was significantly related to a previous diagnosis of AIDS, concurrent neutropenia, the occurrence of sepsis or urinary tract infection, disease relapses, the involvement of non-aeruginosa Pseudomonas spp., and a lethal outcome, compared with community-acquired infection. Our experience (the largest reported to date) confirms that Pseudomonas spp. (including non-aeruginosa Pseudomonas spp. organisms) is responsible for remarkable morbidity and mortality among patients with HIV infection, and may pose relevant problems to clinicians and microbiologists involved in the care of HIV-infected patients.

To assess the role of Moraxella catarrhalis complications in the setting of HIV disease, and to evaluate their occurrence and outcome according to several epidemiological, clinical, and laboratory parameters, the clinical records of 2123 consecutive HIV-infected patients hospitalized in a 9-year period were retrospectively reviewed, and 4 cases of community-acquired M. catarrhalis pneumonia were identified. Three adult patients had a diagnosis of AIDS and severe concurrent immunodeficiency (with a CD4+ lymphocyte count below 60 cells/microL), while the fourth case involved a child with vertical HIV disease. Leukopenia and neutropenia were never present, but no patient received a potent antiretroviral regimen at the time of disease onset. A concurrent respiratory infection by Streptococcus pneumoniae and Mycobacterium tuberculosis was recognized in 2 of 4 patients. Isolated M. catarrhalis strains were susceptible to all tested antimicrobial compounds (save ampicillin in 2 cases), and appropriate antimicrobial treatment led to clinical and microbiological cure in all described episodes. Only 8 cases of HIV-associated Moraxella spp. disease have been reported to date in seven different literature reports (6 cases of pneumonia, and 1 of septicemia). According to our experience, M. catarrhalis may be responsible for appreciable morbidity among patients with advanced HIV infection, especially when a low CD4+ cell count or coexisting respiratory disease are present. Clinicians and microbiologists who care for HIV-infected patients should carefully consider the potential pathogenic role of Moraxella spp. organisms.

Cytomegalovirus (CMV) infection was one of the most common opportunistic infections in AIDS patients, leading to blindness or life-threatening disease in about 40% of patients in the later stages of AIDS before highly active antiretroviral therapy (HAART). In a retrospective multicenter study we investigated the incidence of CMV retinitis and organ involvement in Northern Italy before (1995 and 1996) and after the introduction of HAART (1997 and 1998) as well as the data regarding CMV antigenemia. We found a sharp drop in the incidence of CMV disease in AIDS patients as well as a decline in the incidence of relapses of CMV-disease after the widespread introduction of HAART. Moreover, there was a decrease in the incidence of antigenemia-positive cases in AIDS patients in the era of HAART and the median CMV viral load was significantly higher in patients who didn't receive HAART than in patients who received HAART (p = 0.001, t test).

Summary Case report A severe and complicated Streptococcus pneumoniae meningitis, prompting the diagnosis of a concurrent occult HIV infection, is presented. The initial finding of a remarkable lymphopenia suggested the study of T-lymphocyte subsets, which disclosed a very low CD4 + cell count (below 60 cells/μL). Subsequently, our patient tested positive at HIV serology, and showed an elevated plasma viral load. Despite a favorable in vitro susceptibility profile of the isolated S. pneumoniae strain, and a timely and adequate antibiotic treatment (ceftriaxone and chloramphenicol, followed by ticarcillin-clavulanate plus netilmicin), our patient experienced a very slow clinical improvement, and suffered from permanent neurological sequelae, including severe bilateral hypacusia of neurological origin. During the subsequent 18-month follow-up, a triple combination antiretroviral treatment obtained a significant improvement of all laboratory markers of HIV disease progression. Comments Although S. pneumoniae is a frequent and well-recognized pathogen in the setting of HIV infection, only 25 cases of HIV-associated pneumococcal meningitis have been reported to date, none of them as the presenting illness of HIV disease. Our case report focuses on the potential occurrence of S. pneumoniae meningitis as the first manifestation of an occult, underlying HIV infection. Provided that HIV infection acts as a risk factor for invasive pneumococcal disease, the occurrence of such an illness should prompt a search for an underlying immunodeficiency, especially in the absence of concurrent systemic diseases.

Objective: To assess the role of Flavobacterium spp. infection in patients with HIV disease. Methods: Clinical charts of 2412 consecutive HIV-infected patients hospitalized in a 8-year period were retrospectively reviewed, to identify all cases of Flavobacterium spp. infections, and to evaluate their occurrence and outcome according to several epidemiological, clinical, and laboratory parameters. Results: Six patients out of 2412 (0.25%,), developed Flavobacterium spp. complications: septicaeama in five cases, and pneumonia in the remaining patient, with F. meningosepticum and F. odoratum isolated in two cases and one case, respectively, and unnamed Flavobacterium spp. organisms in the remaining three cases. Flavobacterium spp. organisms were responsible for six out of 1939 overall episodes of non-mycobacterial bacterial diseases observed in our patient group (0.31%). All patients were severely immunocompromised, showing a prior diagnosis of AIDS, a mean CD4+ lymphocyte count of 64.2 (range 12–187) cells/μl, and a mean neutrophil count of 1.143 (range 700–1600) cells (range 700–1600) cells/μl. Antibiotic, corticosteriod, or cotrimoxazole treatment was carried out during the month preceding disease onset by three, two and five patients, respectively Community-acquired and nosocomial Flavobacterium spp. disease were equally frequent, but the latter occurred with a significantly lower mean neutrophil and CD4+ cell count. Antimicrobial susceptibility assays showed complete sensitivity to ciprofloxacin, and variable resistance to ureidopenicillins, ceftazidirne, imipenem, aztreonam, and aminoglycosides. An appropriate antimicrobial regimen obtained clinical and microbiological cure in all cases, in absence of related mortality or relapses. Conclusions: Since only one episode of HIV-associated F. (Sphingobacterium) multivorum complication has been described to date, our series represents the largest one dealing with Flavobacterium spp. infection in the setting of HIV disease. Our experience suggests that Flavobacterium spp. organisms may play a pathogenic role in patients with advanced HIV disease, even when some commonly recognized risk factors are lacking (i.e. indwelling catheters, instrumentation, IV drug abuse), while a very love CD4+ lymphocyte count, leukopaenia-neutropaenia, and concurrent AIDS-related infectious complications may act as important predisposing factors. In view of the infrequent occurrence of these infections, early suspicion is essential for both clinicians and microbiologists facing immunocompromised patients at risk for invasive bacterial complications. Flavobacterium spp. organisms should be taken into consideration as nosocomial- or community-acquired opportunistic pathogens, due to their relationship with advanced immunodeficiency and their elevated resistance to many antimicrobial agents commonly used against Cram-negative bacterial pathogens.

Summary A survey was carried out in a population of 503 HIV-infected patients attending a tertiary care centre of infectious diseases, to evaluate the spontaneously reported use of alternative therapeutic regimens for HIV disease. One-hundred and seventy-one out of the 412 evaluable patients (41.5%) used at least one unorthodox therapy within the previous 3 months. The recourse to non-conventional therapies increased significantly according to clinical and immunological progression of HIV disease, while no significant relationship was found when age, gender, risk for HIV infection, and duration of known HIV disease were assessed. Patients involved in alternative modes of treatments were more likely to refuse (or follow with poor compliance) antiretroviral therapy and/or anti- Pneumocystis carinii chemoprophylaxis. An elevated percentage of family physicians (46.2%) were unaware of alternative choices made by their patients. Finally, although 81.3% of individuals experiencing non-conventional treatments perceived satisfactory effects on their cenesthesis and health, a significant clinical and/or virological and/or immunological worsening of HIV disease occurred in more than 85% of patients failing to take properly antiretrovirals and/or P carinii prophylaxis.