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Biomedical subjects

Roberto Cauda

Publications and source records attributed to Roberto Cauda.

At least 37 records · Page 2Linked to original sources
PubMed2005

Macrophage chemoattractant protein-1 levels in cerebrospinal fluid correlate with containment of JC virus and prognosis of acquired immunodeficiency syndrome--associated progressive multifocal leukoencephalopathy.

In the highly active antiretroviral therapy (HAART) era, the role of the inflammatory response in acquired immunodeficiency syndrome (AIDS)-related progressive multifocal leukoencephalopathy (PML) remains controversial. In this study, JC virus DNA load and levels of cytokines were determined in cerebrospinal fluid (CSF) from 32 human immunodeficiency virus (HIV)-1-infected patients with confirmed PML who underwent HAART; cytokines were also measured in 12 HIV-positive controls. Predictors of survival were analyzed by Cox's models. Macrophage chemoattractant protein (MCP)-1 levels were significantly higher in PML patients than in controls (mean +/- SD, 2.45 +/- 0.64 versus 1.32 +/- 0.64 log(10) pg/ml, P<.0001). In PML patients, the higher concentration of MCP-1 correlated with lower JC viral load (r=-.405, P=.036). Higher concentrations of MCP-1 in CSF were associated with longer survival on HAART after adjusting for CD4 counts (for each log(10) pg/ml higher, hazard ratio for death 0.28, 95% confidence interval 0.08--1.00). Predictors of shorter survival were lower baseline CD4 counts, higher JCV DNA concentrations, lower Karnofsky, and no prior HAART exposure. These results showed that higher CSF levels of MCP-1, an inflammatory cytokine, were correlated with better prognosis in HAART-treated patients with PML.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Dental care and HIV-infected individuals: are they equally treated?

OBJECTIVE: To investigate the problems in seeking dental care faced by HIV-positive individuals in Italy. METHODS: A multicenter observational study was performed by distributing an anonymous self-administered questionnaire to patients of six public healthcare facilities specialized in the treatment of individuals with HIV infection. The questions concerned personal data potentially correlated with discrimination, the patient-dentist relationship before and after HIV diagnosis, and the reasons for seeking dental care in public facilities. We also evaluated the patients' discomfort in the patient-dentist relationship after HIV diagnosis, performing univariate and multivariate analyses. RESULTS: Of the 1,500 questionnaires distributed; 883 were filled-out completely. A total of 630 persons received dental care after HIV diagnosis: 209 (33.2%) did not tell the dentist that they were seropositive. Of those who did, 56 were refused care. For patients treated by a private dentist, having been treated by the same dentist before diagnosis was a risk factor for great discomfort in the patient-dentist relationship (P < 0.002). Being treated in public facilities was associated with having received dental care after HIV diagnosis (P < 0.001) and a primary school education (P < 0.001). CONCLUSIONS: There exist episodes of discrimination on the part of some dentists, and a relatively high proportion of HIV-positive persons do not disclose their seropositivity to the dentist. Dentists should be provided with training for promoting both ethically acceptable practices and suitable clinical management of HIV-positive persons.

Analysis of Variance↗
PubMed2005

Reduced rate of diagnostic positive detection of JC virus DNA in cerebrospinal fluid in cases of suspected progressive multifocal leukoencephalopathy in the era of potent antiretroviral therapy.

Fifty-nine human immunodeficiency virus (HIV)-infected patients with suspected progressive multifocal leukoencephalopathy and 224 controls were tested for JC virus (JCV) DNA in cerebrospinal fluid by PCR. The diagnostic positive detection rate dropped from 89.5% (95% confidence intervals of 75.5 to 103.5%) in the pre-highly active antiretroviral therapy (HAART) era to 57.5% (95% confidence intervals of 42.1 to 72.9%) in the HAART era; the specificity remained unchanged. Predictors of failure to detect JCV DNA were exposure to HAART at disease onset and higher CD4 counts.

Adult↗
PubMed2005

HIV protease inhibitors prevent mitochondrial hyperpolarization and redox imbalance and decrease endogenous uncoupler protein-2 expression in gp 120-activated human T lymphocytes.

It has been demonstrated that HIV protease inhibitors (Pls) are able to inhibit apoptosis of both infected and uninfected T cells. It was hypothesized that the mechanisms underlying this effect are associated with a specific activity of these drugs against mitochondrial modifications occurring in the execution phase of apoptosis. In this work, we investigated the activity of PIs towards the early changes occurring in mitochondrial membrane potential in freshly isolated uninfected human T lymphocytes sensitized to CD95/Fas-induced physiological apoptosis via pre-exposure to HIV envelope protein gp120. The results obtained clearly indicate that PIs are capable of hindering early morphogenetic changes bolstering T cell apoptosis, that is, cell polarization and mitochondrial hyperpolarization. The target effect on mitochondria appeared to be characterized by a specific activity of Pls in the maintenance of their homeostasis either in intact cells or in cell-free systems, that is, isolated mitochondria. Pls seem to act as boosters of mitochondrial defense mechanisms, including modulation of endogenous uncouplers. These results add new insights in the field of PI mitochondrial toxicity mechanisms and pharmacological perspectives for the use of these drugs in the control of immune system homeostasis.

Apoptosis↗
PubMed2004

Older age does not influence CD4 cell recovery in HIV-1 infected patients receiving highly active antiretroviral therapy.

BACKGROUND: Diagnosis of HIV infection is recently occurring with increasing frequency in middle-aged and in older individuals. As HAART became available, a minimal beneficial effect on immunological outcome in older in respect of younger subjects has been reported. In fact, both the intensity and the rapidity of the immunological response appeared to be reduced in elderly subjects. On the contrary, only few reports have indicated a similar immunological outcome both in older and younger HIV-positive subjects. Interestingly, older age did not seem to significantly affect the long-term virological outcome of HAART treated subjects. METHODS: To characterise epidemiological and clinical features of older HIV+ subjects, a prospective case-control study was performed: 120 subjects >/= 50 and 476 between 20 and 35 years were initially compared. Subsequently, to better define the impact of HAART on their viro-immunological response, 81 older were compared with 162 younger subjects. RESULTS: At baseline cases presented significantly lower TCD4+ cell number and were more frequently affected by comorbid conditions. Under HAART a statistically significant increase in TCD4+ cell number was observed in cases and controls. At multivariate analysis, there was no statistically significant difference between cases and controls regarding viro-immunological response. CONCLUSIONS: Although older subjects present a more severe HIV infection, they can achieve, under HAART, the same viro-immunological success as the younger individuals.

Adult↗
PubMed2004

Liver fibrosis stage predicts early treatment outcomes with peginterferon plus ribavirin in HIV/hepatitis C virus co-infected patients.

Thirty-six HIV-infected patients with chronic hepatitis C treated with peginterferon alpha-2a or 2b plus ribavirin were analysed in a prospective observational study. The were 15 (42%) treatment discontinuations; bt intent-to-treat virological responders were 19 (53%) at week 24. A higher fibrosis score predicted premature discontinuation of hepatitis C virus (HCV) therapy and a lack of early virological response. Female sex and HCV genotype predicted early virological responses. Results support the early treatment of HCV in co-infected individuals.

Adult↗
PubMed2004

Anti-retroviral therapy with protease inhibitors decreases virulence enzyme expression in vivo by Candida albicans without selection of avirulent fungus strains or decreasing their anti-mycotic susceptibility.

Highly active anti-retroviral therapies (HAART) with human immunodeficiency virus (HIV) protease inhibitors (PIs) or nonnucleoside reverse-transcriptase inhibitors (NNRTI) were compared for their effect on prevalence, aspartyl proteinase (Sap) production and the biotypes and anti-mycotic sequential susceptibility of Candida spp. isolates from the oral cavity in a longitudinal prospective study. HAART-PI, but not HAART-NNRTI strongly inhibited Sap expression in the oral cavity without exerting any consistent effect on the role of Candida spp. isolation or selection of low virulence or anti-mycotic resistant fungus biotype. More importantly, the sequential isolates of Candida albicans from HAART-PI, but not those from suspended HAART-NNRTI, showed an increased Sap production in vitro. While further demonstrating that HIV-PI inhibit Sap expressions, our results do not support the view that the mentioned inhibition could eliminate Candida or its selection of the oral cavity.

AIDS-Related Opportunistic Infections↗
PubMed2004

Deep salvage with amprenavir and lopinavir/ritonavir: correlation of pharmacokinetics and drug resistance with pharmacodynamics.

The safety, efficacy, and mutual interactions of combination amprenavir with lopinavir/ritonavir as deep salvage treatment were investigated in a prospective 24-week pilot study. HIV-infected patients (n = 22) with virologic failure to nucleoside reverse transcriptase inhibitors (NRTIs), non-NRTIs, and at least 2 protease inhibitors received 400/100 mg of lopinavir/ritonavir with 600 mg of amprenavir every 12 hours combined with NRTIs. Patients receiving the same doses of lopinavir/ritonavir (n = 10) or amprenavir with ritonavir (n = 8) were chosen as controls for pharmacokinetic analyses. Mean changes from baseline HIV RNA levels and CD4 counts after 24 weeks were -1.13 log10 copies/mL and +88 x 10 cells/L, respectively. The mean plasma trough concentration (Cmin)and peak concentration (Cmax) of amprenavir were 104% and 228% lower and the Cmin of lopinavir was 46% lower in patients in whom the drugs were coadministered than in controls. There were 4 permanent drug discontinuations because of toxicity. An inhibitory quotient (IQ) of amprenavir higher than 0.8 was the best predictor of virologic outcome at 24 weeks, even after adjusting for amprenavir Cmin or phenotypic susceptibility. Deep salvage therapy using lopinavir/ritonavir with amprenavir is sufficiently safe and shows partial efficacy. When these drugs are coadministered, therapeutic drug monitoring should be employed and the IQ can be used to determine target drug levels.

Adult↗
PubMed2004

Anti-HIV effects of chloroquine: inhibition of viral particle glycosylation and synergism with protease inhibitors.

OBJECTIVE: We tested the effects of chloroquine (CQ) on glycosylation of HIV particles and in combination with protease inhibitors (PIs) on HIV replication and on P-glycoprotein (P-gp)/multidrug resistance protein-1 (MRP1). DESIGN: CD4 cell lines were infected with laboratory strains and peripheral blood mononuclear cells were infected with primary isolates for evaluation of the anti-HIV effects. Peripheral blood lymphocytes were evaluated for of P-gp and MRP1 functions. METHODS: HIV replication was assessed by enzyme-linked immunosorbent assay. HIV glycosylation was measured by metabolic labeling of viral particles with [H] glucosamine. Synergism was tested using isobolograms. P-gp and MRP1 functions were assayed using rhodamine 123 (Rh123) and carboxyfluorescein (CF) efflux assays, respectively. RESULTS: CQ alone inhibited HIV replication and glycosylation in a dose-dependent manner. In combination with indinavir (IDV), ritonavir, or saquinavir (SQV), CQ had a synergistic effect at concentrations found in plasma of subjects receiving malaria prophylaxis. CQ decreased the 50% effective concentration of IDV in primary isolates from Africa and restored the response to IDV or SQV in 3 PI-resistant isolates. CQ increased the block of Rh123 and CF efflux activity exerted by PIs. CONCLUSION: The inhibitory effects of CQ on HIV glycosylation are associated with synergistic effects in combination with PIs. The CQ/PI combination exerts combined inhibitory effects on P-gp and MRP1 function.

Anti-HIV Agents↗
PubMed2004

HIV infection, HAART, and endothelial adhesion molecules: current perspectives.

In this review we summarise the data on the effects of HIV infection and its therapy with antiretroviral drugs on adhesion molecules, considered to be potential biomarkers of endothelial cell function. This is a recent area of interest, given the unexpected associations between antiretroviral therapy, metabolic alterations of lipid profile, and the risk of cardiovascular disease in the absence of clear pathogenetic links. Although convincing prospective data are still scarce, it seems timely to elucidate the potential value of non-invasive, inexpensive tests for predicting cardiovascular risk in HIV-infected patients undergoing highly active antiretroviral therapy (HAART). Endothelial function, the most plausible link between infection, inflammation, and atherosclerosis, has been investigated since the beginning of the HIV epidemic. Increased concentrations of soluble adhesion molecules, such as those from the selectin and immunoglobulin families, have consistently been reported in HIV-positive patients. The introduction of HAART has renewed interest in the study of endothelial function in HIV-positive patients, in view of some HAART-related metabolic abnormalities (hyperlipidaemia, hyperglycaemia, fat redistribution) and several large reports of premature coronary artery disease. Whether HAART reduces endothelial injury associated with HIV infection or contributes to further endothelial cell activation is still a matter of controversy. Also unclear is whether HAART acts directly or indirectly, and if protease inhibitors and other classes of antiretroviral drugs differ in their proatherosclerotic effects. This article attempts to define the state of these emerging issues, identifies areas of controversy and of potential clinical relevance, and suggests some directions for future research.

Antiretroviral Therapy, Highly Active↗
PubMed2003

ESBL-producing multidrug-resistant Providencia stuartii infections in a university hospital.

OBJECTIVES: To investigate the epidemiological and clinical findings of extended-spectrum beta-lactamase (ESBL)-producing Providencia stuartii infections in a large Italian university hospital. PATIENTS AND METHODS: All consecutive episodes of P. stuartii infection that occurred during 1999-2002 were included in the study. For each patient, we recorded the area of hospitalization and drug susceptibility of the P. stuartii strains. Patients with ESBL-producing P. stuartii infection were considered cases and those with non-ESBL-producing P. stuartii infection were used as controls. RESULTS: One hundred and sixteen (52%) out of 223 P. stuartii strains collected during the study period were found to be ESBL-producing. On the basis of PCR and DNA sequencing experiments, TEM-52 was identified in 87% of isolates and TEM-72 in 13%. All ESBL-producing P. stuartii infections were nosocomially acquired. The prevalence increased from 31% of P. stuartii infections in 1999 to 62% in 2002 (P = 0.04). All 116 strains were classified as ESBL-producing multidrug-resistant P. stuartii, since 88% of the isolates were cross-resistant to ciprofloxacin and amikacin and the other 12% were cross-resistant to ciprofloxacin and gentamicin. At logistic regression analysis, advanced age (P < 0.001), previous hospitalization (P < 0.01), neoplastic disease (P < 0.001) and previous antibiotic therapy (P < 0.001) were independent risk factors for the development of ESBL-producing infections. CONCLUSIONS: This 4 year surveillance of Providencia complaints clearly indicates that infections caused by ESBL-producing multidrug-resistant P. stuartii are an emerging problem.

Adult↗
PubMed2003

Mitochondrial membrane hyperpolarization hijacks activated T lymphocytes toward the apoptotic-prone phenotype: homeostatic mechanisms of HIV protease inhibitors.

A decrease of mitochondrial membrane potential has been hypothesized to be a marker of apoptotic cells, including activated T lymphocytes. It was recently demonstrated that HIV protease inhibitors, independently from any viral infection, can hinder lymphocyte apoptosis by influencing mitochondrial homeostasis. To analyze the mechanisms underlying these effects, a specific study was undertaken in both resting and activated human PBL exposed to either receptor (e.g., anti-Fas)- or nonreceptor (e.g., radiation)-mediated apoptotic stimuli. T cell activation was found to be accompanied by a significant increase in mitochondrial membrane potential, or hyperpolarization, which was undetectable in resting cells. We also detected apoptotic hindering by HIV protease inhibitors only in activated T lymphocytes. This was apparently due to the ability of these drugs to block activation-associated mitochondria hyperpolarization, which, in turn, was paralleled by an impairment of cell cycle progression. Remarkably, protease inhibitors also prevented zidovudine-mediated mitochondrial toxicity. Finally, HIV-infected cells from naive patients behaved identically to activated T cells, displaying hyperpolarized mitochondria, while lymphocytes from patients under highly active antiretroviral therapy (which included HIV protease inhibitors) seemed to react as resting cells. Altogether these results clearly indicate that the hyperpolarization state of mitochondria may represent a prerequisite for the sensitization of lymphocytes to the so-called activation-induced cell death. They also suggest that HIV protease inhibitors, by interfering with induction of the mitochondrial hyperpolarization state, can result in cell survival even independent of any viral infection.

Adult↗
PubMed2003

Effects of chloroquine on viral infections: an old drug against today's diseases?

Chloroquine is a 9-aminoquinoline known since 1934. Apart from its well-known antimalarial effects, the drug has interesting biochemical properties that might be applied against some viral infections. Chloroquine exerts direct antiviral effects, inhibiting pH-dependent steps of the replication of several viruses including members of the flaviviruses, retroviruses, and coronaviruses. Its best-studied effects are those against HIV replication, which are being tested in clinical trials. Moreover, chloroquine has immunomodulatory effects, suppressing the production/release of tumour necrosis factor alpha and interleukin 6, which mediate the inflammatory complications of several viral diseases. We review the available information on the effects of chloroquine on viral infections, raising the question of whether this old drug may experience a revival in the clinical management of viral diseases such as AIDS and severe acute respiratory syndrome, which afflict mankind in the era of globalisation.

Acquired Immunodeficiency Syndrome↗
PubMed2003

Interpretation systems for genotypic drug resistance of HIV-1.

Genotypic assays are widely used tools for determining human immunodeficiency virus type 1 (HIV-1) drug resistance and for guiding treatment changes in patients failing antiretroviral therapy. Several systems have been developed to interpret the complex influence of key amino acid substitutions of the enzymes targeted by therapy on the phenotypic susceptibility or clinical response to available antiretroviral agents. This overview identifies 21 systems giving an interpretation on how amino acid substitutions affect phenotypic drug susceptibility or clinical activity of anti-HIV-1 agents. There was substantial variability in the mechanisms underlying the interpretations, the nature of the systems, their intended use, the source type of their knowledge base, and their update and output. Most of the systems could be accessed for free on the internet, functioned as rule-based algorithms updated by experts and at least partially based on literature evidence, and offered an automated report through a software. Nevertheless, the rule base was not always clarified. An update of the rules and the clinical validation of the systems are presented to help in the critical evaluation of their possible use. Importantly, only 8 systems were intended for clinical use and 5 of these had at least partially undergone clinical validation.

Anti-HIV Agents↗