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Biomedical subjects

R Cauda

Publications and source records attributed to R Cauda.

At least 19 recordsLinked to original sources
PubMed2006

Key questions in antiretroviral therapy: Italian Consensus Workshop (2005).

A panel of leading Italian specialists in infectious diseases, virologists and immunologists met in Rome in 2005 to review critical data and discuss recommendations for each of the key questions in antiretroviral therapy today: When to start treatment? How to start? When to switch? What to switch to? Whether to stop or not to stop treatment, and how? The method of a nominal group meeting was used and recommendations were graded for their strength and quality using a system based on the one adopted by the Infectious Diseases Society of America. Main conclusions are summarized and critically discussed in this consensus statement, as well as some of the most recent data supporting these recommendations are provided.

Anti-HIV Agents↗
PubMed2006

Aetiological factors related to a positive direct antiglobulin test result in human immunodeficiency virus-infected patients.

BACKGROUND AND OBJECTIVES: The aim of this study was to examine the clinical importance and causes of a positive result in the direct antiglobulin test (DAT) in human immunodeficiency virus-infected (HIV(+)) patients. We therefore studied haematological parameters in outpatient samples, and also analysed the impact of highly active anti-retroviral therapy (HAART) on the DAT results. STUDY DESIGN AND METHODS: Haematological parameters, clinical stages, chemo-antibiotic treatments and HAART treatment were studied to determine any relationships with DAT results in 115 consecutive HIV(+) patients. RESULTS: Significantly lower haemoglobin (Hb) levels were detected in patients with HIV who had a positive DAT result. Hepatitis C virus (HCV) co-infection (odds ratio 2.529) and trimethoprim-suphamethoxazfole (TMP-SMX) prophylaxis (odds ratio 3.751) had a significant association with DAT positivity. Patients receiving HAART were less likely to have a positive DAT [odds ratio (OR) 0.383; P = 0.035]. Among the patients treated with TMP-SMX, those with a positive DAT had lower Hb levels (11.9 g/dl) than those with a negative DAT (14.2 g/dl; P = 0.04). HCV antibody positivity and TMP-SMX prophylaxis showed a cumulative effect on positive DATs (OR 4.533). The surface exploratory analysis indicated the distribution of the positive DATs in relationship with the CD4(+) count and Hb levels. CONCLUSIONS: Significantly lower Hb levels were detected in DAT-positive HIV(+) patients. HCV co-infection and TMP-SMX prophylaxis appear to confer an increased risk of DAT positivity. The presence of red blood cell autoantibodies may be associated with anaemia in HIV disease in the absence of overt haemolysis.

Anemia↗
PubMed2004

Hospital infection control in Europe: evaluation of present practice and future goals.

The objective of this study was to assess current infection control practice in Europe and its structure, future research priorities, and how infection control should be organised. A questionnaire was sent to 223 hospital infection control physicians throughout Europe, of whom 54 in 18 countries responded. With respect to future research priorities in infection control in Europe, the largest proportion (69%) of the infection control specialists sampled expressed the need for standardisation of surveillance systems for international comparison of nosocomial infection rates. The results of this survey might help to create a basis for standardised guidelines which take into account European-wide interests.

Cross Infection↗
PubMed2004

Hospital-acquired candidemia in HIV-infected patients. Incidence, risk factors and predictors of outcome.

A retrospective case-control study was performed to analyze hospital-acquired candidemia in HIV-positive patients. To understand the impact of Highly Active Antiretroviral Therapy (HAART) on the incidence of nosocomial candidemia, two time periods were compared: A (1992-1996) and B (1997-2001). 32 out of 38 (84%) cases of candidemia were hospital-related. A significant reduction in the incidence of all cases of hospital-acquired candidemia has been observed in the post-HAART in respect to pre-HAART period (0.09 episodes vs. 1.1 per 100/py). Multivariate analysis showed that the presence of central venous catheter was the only variable independently associated with the development of nosocomial candidemia. The overall mortality rate was 59%. Univariate analysis indicated three prognostic indicators: presence of concomitant opportunistic infections, isolation of non-albicans Candida species; neutropenia. Multivariate analysis of prognostic indicators showed that isolation of non-albicans Candida species is the only independent variable. Despite the use of HAART, this disease still represents a severe complication of advanced stage of AIDS.

Adult↗
PubMed2003

Correlation between cidofovir-associated uveitis and failing immunorestoration during HAART.

In order to elucidate the factors related to the development of cidofovir-associated uveitis in AIDS patients receiving highly active antiretroviral therapy, the characteristics of 17 AIDS patients with Cytomegalovirus retinitis ( n=10) or progressive multifocal leukoencephalopathy ( n=7) treated with intravenous cidofovir were evaluated. Six cases of cidofovir-associated uveitis occurred among the patients with retinitis. No cases were detected among the patients with progressive multifocal leukoencephalopathy. Stepwise linear regression analysis revealed a significantly higher HIV-viremia level ( P=0.01) and a significantly lower CD4+ cell count ( P=0.009) among cases at the time of uveitis onset in comparison with patients who did not develop uveitis. Thus, cidofovir-associated uveitis seems to occur more frequently in AIDS patients with retinitis in whom highly active antiretroviral therapy fails to restore immunity.

Acquired Immunodeficiency Syndrome↗
PubMed2003

Impact of highly active antiretroviral therapy (HAART) on the incidence of bacterial infections in HIV-infected subjects.

The aim of this study was to evaluate the effect of highly active antiretroviral therapy (HAART) on the incidence of bacterial infections in HIV-infected patients. Two time periods were compared: (A) January 1992-December 1995 (before HAART) and (B) January 1997-December 2000 (after HAART). During the study periods, we observed 931 patients with bacterial infections, i.e. 322 with bacteremia, 369 with bacterial pneumonia and 240 with urinary tract infections, out of 4,242 HIV-infected subjects admitted to the Department of Infectious Diseases of a large university hospital. By comparing the overall incidence of bacterial infections during periods A and B, a statistically significant difference, from 32% to 18% (p<0.01), was observed. Analysis of risk factors of community- and hospital-acquired bacterial infections did not significantly differ in the two study periods. This study establishes that a significant reduction in bacterial infection incidence occurred in HIV-infected subjects when HAART became the standard therapy for HIV infection.

Adult↗
PubMed2001

Glycopeptide resistance among coagulase-negative staphylococci that cause bacteremia: epidemiological and clinical findings from a case-control study.

A 1-year prospective case-control study (ratio of control patients to case patients, 3:1) was performed to assess the incidence, risk factors, and genotypic patterns of bacteremia caused by glycopeptide-resistant coagulase-negative staphylococci (CoNS) and their correlation with hospital glycopeptide use. Among 535 subjects with CoNS bacteremia, 20 subjects had a glycopeptide-resistant strain (19 strains were resistant to teicoplanin and 1 was resistant to both teicoplanin and vancomycin). The percentage of resistant isolates recovered in 1 year was 8% in intensive care units and 3% and 2% in medical and surgical wards, respectively. Genotypic analysis of resistant strains showed different patterns with a high degree of polymorphism. Use of glycopeptides in individual wards was not statistically associated with the percentage of resistance. Previous exposure to beta-lactams and glycopeptides, multiple hospitalization in the previous year, and concomitant pneumonia were significantly associated with the onset of glycopeptide-resistant CoNS bacteremia. Mortality rates were 25% among case patients and 18% among control patients, and they were significantly higher among patients who presented with concomitant pneumonia and a high Acute Physiology and Chronic Health Evaluation III score.

Aged↗
PubMed2001

Better response to chemotherapy and prolonged survival in AIDS-related lymphomas responding to highly active antiretroviral therapy.

OBJECTIVES: To evaluate the impact of response to highly active antiretroviral therapy (HAART) on the natural history of AIDS non-Hodgkin's lymphoma (NHL) and to analyse the feasibility, efficacy and toxicity of HAART in combination with chemotherapy. DESIGN: Prospective observational study in two AIDS clinical centres in Italy. METHODS: All consecutive HIV-infected patients with NHL were included (n = 44; 48% high-risk group) and prospectively followed for 27 months. HAART was administered concomitantly with chemotherapy. The association between response to HAART and clinical presentation, response to chemotherapy and toxicity was analysed by univariate and multivariate models. Survival analysis was performed by Kaplan-Meier estimates and the Cox proportional hazards regression model. RESULTS: A complete response (CR) to chemotherapy was achieved in 71% of HAART responders and 30% of non-responders. Virological response to HAART was the only variable associated with tumour response on multivariate analysis. A higher relative dose intensity (RDI) of chemotherapy was administered in patients with virological response compared with those without. The probability of 1 year survival was higher in patients with virological or immunological response. At Cox regression analysis, immunological response, a higher RDI and a CR to chemotherapy were all associated with a reduced risk of death. CONCLUSION: In HIV-infected patients with NHL, response to HAART was strongly associated with a better response to chemotherapy and prolonged survival. Concurrent treatments were well tolerated, and HAART-responder patients could receive a higher RDI of chemotherapy. In patients with AIDS lymphomas, combining HAART with chemotherapy could be a feasible and effective approach.

Adult↗
PubMed2001

HIV-protease inhibitors contribute to P-glycoprotein efflux function defect in peripheral blood lymphocytes from HIV-positive patients receiving HAART.

P-glycoprotein (P-gp) has been found expressed in normal human cells, such as bone marrow and peripheral blood cells. The aim of this study was to investigate whether HIV-protease inhibitors (HIV-PIs) interact with P-gp efflux function in normal human peripheral blood lymphocytes (PBLs) and CD34+ progenitor cells. Moreover, we analyzed the in vivo effect of HIV-PIs on P-gp function in PBLs from HIV-infected patients receiving highly active antiretroviral therapy (HAART). We found that HIV-PIs (i.e., ritonavir, saquinavir, nelfinavir and indinavir) interfere with P-gp function in normal PBLs as demonstrated by the reduced efflux of rhodamine 123 (Rh123). This effect was dose-dependent and suggested the following hierarchy: ritonavir > saquinavir > nelfinavir > indinavir. We further analyzed the effect of HIV-PIs on the P-gp function in specific PBLs subsets. Our results show an HIV-PI-induced inhibition of P-gp function in CD4+ and CD8+ T cell subsets, mostly caused by the effect on the naive compartment of both CD4+ and CD8+ T cells. The same inhibitory effect was found in CD34+ hematopoietic progenitor cells. With respect to the in vivo evaluation of P-gp function in PBLs from HIV-infected patients, we found reduced levels of Rh123 efflux that reached the lowest value in AIDS patients receiving HAART. We concluded that HIV-PIs interfere with P-gp function in major cellular targets for HIV infection, such as CD4+ T cells and CD34+ progenitor cells. This ability may contribute to P-gp efflux function defect found in HIV-infected patients and suggests that drug interaction studies are crucial to an overall understanding of the effects of this important group of drugs.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

Expression of P-170 glycoprotein sensitizes lymphoblastoid CEM cells to mitochondria-mediated apoptosis.

Multidrug resistance caused by P-glycoprotein (P-170) is a phenomenon by which cells exposed to a single drug acquire resistance to other structurally and functionally unrelated drugs. This is a widespread phenomenon described in vivo in the management of infectious as well as non-infectious diseases. Several in vitro models have been developed in order to evaluate physiopathological properties of P-170. Among these are P-170-expressing variants of the human T-lymphoblastoid CEM cell line called VBL100. As a general rule, drug resistance normally results in resistance to apoptosis induction. By contrast, a paradoxical activity is exerted in this cell model by the cytokine tumour necrosis factor-alpha (TNF-alpha), which is capable of inducing apoptosis in P-170-expressing variants better than in wild-type (wt) cells. In the present study we partially address the mechanisms underlying this activity. In fact, the susceptibility of VBL100 cells to TNF-alpha appears to be specifically due to the depolarization of their mitochondrial membrane, a key factor for apoptotic induction. The same was observed with staurosporine, a specific mitochondrion-mediated proapoptotic chemical probe. Conversely, other proapoptotic stimuli, such as Fas/CD95 or the anti-cancer drug etoposide, did induce significant cell death in wild type cells only. Thus, schematically, mitochondrially dependent stimuli appeared to be more effective in VBL100-cell killing, while 'physiological' stimuli showed the opposite behaviour. Importantly, under steady-state conditions, VBL100 cells displayed per se a mitochondrial membrane hyperpolarization that appeared strictly related to their high susceptibility to specific apoptotic stimuli. In conclusion, the study of a well-established cell model such as that represented by the wt/VBL CEM lymphoid cell line seems to suggest that the multidrug resistance phenotype can specifically sensitize cells towards 'unphysiological', mitochondria-associated cell death cascade or, in the same fashion, it could shift cells from type I (mainly plasma membrane-associated) towards type II (mainly mitochondrial membrane-associated) phenotype.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

Changes in incidence and risk factors of Mycobacterium avium complex infections in patients with AIDS in the era of new antiretroviral therapies.

The aim of the study presented here was to determine the incidence, risk factors and prognostic indicators of Mycobacterium avium complex (MAC) infection in HIV-infected subjects prior to and after the introduction of highly active antiretroviral therapy (HAART). In the HAART era, the incidence of MAC infection decreased significantly from 3.7 to 0.9 per 100 person-years. Using logistic regression analysis, a high acute physiology and chronic health evaluation (APACHE) III score, a low number of CD4+ cells/ mm3 and a high level of HIV viremia were found to be independent predictors of the risk to develop MAC disease; however, a high APACHE III score was the only prognostic indicator associated with an unfavourable outcome of a disseminated MAC infection. These results indicate that MAC infections, although considerably less frequent in the HAART era, are still responsible for cases of severe disease.

AIDS-Related Opportunistic Infections↗
PubMed2001

Decreased function of Fas in patients displaying delayed progression of HIV-induced immune deficiency.

INTRODUCTION: In acquired immune deficiency syndrome patients, apoptosis of uninfected lymphocytes may contribute to development of immune deficiency. This process may involve recruitment of Fas by human immunodeficiency virus products. In line with this possibility, the viral envelope glycoprotein gp120 does not induce death of T cells from subjects with the autoimmune/lymphoproliferative syndrome displaying defective Fas function. This study evaluates the possibility that Fas function defects delay progression of HIV-induced immune deficiency. MATERIALS AND METHODS: The susceptibility to Fas-induced cell death was assessed on T cells from 18 'long-term non-progressor', four 'non-progressor', four 'progressor' asymptomatic HIV-1-infected, and nine AIDS patients using anti-Fas monoclonal antibodies. RESULTS: Fas-induced cell death was significantly lower in long-term non-progressors and non-progressors than in normal controls, progressors, and AIDS. The single-patient data showed that 9/18 long-term non-progressors and 3/4 non-progressors, but no progressors or AIDS were resistant to Fas. Analysis of the uninfected parents of two long-term non-progressors displaying decreased Fas-function showed that the mother of one of them and the father of the other displayed the same Fas function defect as their children. Fusion of T cells from Fas-resistant individuals with a Fas-sensitive cell line gave rise to Fas-resistant hybrid lines not carrying HIV, which suggests that the resistant phenotype is due to molecules exerting a dominant negative effect on a normal Fas system. CONCLUSION: These data suggest that Fas-resistance in long-term non-progressors may be due to inherited alterations of the Fas signaling pathway and may be a novel factor in delayed progression.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Potent anti-retroviral therapy with or without cidofovir for AIDS-associated progressive multifocal leukoencephalopathy: extended follow-up of an observational study.

To analyze the clinical efficacy of cidofovir combined with highly active anti-retroviral therapy (HAART) in AIDS-related progressive multifocal leukoencepalopathy (PML), a multicenter observational study was performed. Consecutive HIV-positive patients with histologically or virologically proven PML and at least 4 weeks of treatment after diagnosis were examined: 27 patients were treated with HAART, whereas 16 patients were treated with HAART plus cidofovir 5 mg/kg intravenously per week for the first 2 weeks and every other week thereafter. JC virus DNA was quantified in cerebrospinal fluid (CSF) by PCR. Baseline virologic, immunologic, and clinical characteristics as well as HIV RNA and CD4 responses to HAART were homogeneous between the groups. The median follow-up was 132 weeks. In one case (6%), cidofovir was permanently discontinued because of severe proteinuria. One-year cumulative probability of survival was 0.61 with cidofovir and 0.29 without (log rank test P = 0.02). After adjusting for baseline CD4 counts, JC viral load in CSF, Karnofsky, and use of HAART prior to the onset of PML, the use of cidofovir was independently associated with a reduced risk of death (hazard ratio, 0.21, 95% confidence interval, 0.07-0.65; P = 0.005). A randomized study will definitively establish whether cidofovir confers significant advantage over HAART alone in AIDS-related PML.

AIDS-Related Opportunistic Infections↗
PubMed2001

Nosocomial bacterial pneumonia in human immunodeficiency virus infected subjects: incidence, risk factors and outcome.

The presented study examined the incidence, risk factors and outcome of nosocomial bacterial pneumonia (NBP) in human immunodeficiency virus (HIV)-infected subjects. Forty-two cases of NBP were ascertained by a 5-yr prospective surveillance and were matched to 84 controls. NBP incidence was 10.8 per 10,000 hospital patient-days. In particular, the incidence of NBP was 13.9 per 10,000 patient-days in the period 1994-1996 and 5.6 per 10,000 patient-days in the period 1997-1998 (p=0.01). By using regression analysis, predictors for developing NBP were an increasing value of Acute Physiology and Chronic Health Evaluation (APACHE) III score (p<0.01) and the presence of acquired immune deficiency syndrome (AIDS)-related central nervous system (CNS) diseases (p=0.01). The additional hospital stay attributable to NBP was 15 days. The attributable mortality rate was estimated to be 29%. Nosocomial bacterial pneumonia is more common in patients with advanced human immunodeficiency virus infection, high Acute Physiology and Chronic Health Evaluation III score and central nervous system diseases. Although the incidence of nosocomial bacterial pneumonia, as well of other opportunistic infections, decreased considerably in the era of highly active antiretroviral therapy, it still represents an important cause of mortality.

AIDS-Related Opportunistic Infections↗