Giacomo Magnani

Rhodococcus equi Infection in HIV-positive Subjects: A Retrospective Analysis of 24 Cases

Rhodococcus equi causes a rare infection in immunocompromised hosts. We describe 24 cases of infection in patients with AIDS-related complex (ARC)/acquired immunodeficiency syndrome (AIDS). Pneumonia was always the first manifestation of R. equi infection, but extrapulmonary involvement was also observed. The main sources of bacteria were sputum, bronchial washings and blood. The strains isolated were mainly susceptible to erythromycin, vancomycin, teicoplanin, rifampicin, imipenem and aminoglycosides. Initial treatment should involve an intravenously administered antibiotic combination therapy including imipenem or vancomycin or teicoplanin, followed by orally administered maintenance combination therapy. Drug combinations should be investigated for serum bactericidal activity in vitro. Surgery does not increase survival time and should only be performed in cases that do not respond to antibiotic treatment. Presumptive risks of infection (contact with horses or farm dust, or cohabiting with people affected by R. equi infection) were present in more than 50% of patients. This finding, and the frequency of bacteria in the sputum, are not sufficient proof of transmission between humans, but do suggest the need for respiratory isolation of patients affected by R. equi pneumonia.

Stable changes in CD4+ T lymphocyte miRNA expression after exposure to HIV-1

MicroRNAs (miRNAs) inhibit HIV-1 expression by either modulating host innate immunity or by directly interfering with viral mRNAs. We evaluated the expression of 377 miRNAs in CD4(+) T cells from HIV-1 élite long-term nonprogressors (éLTNPs), naive patients, and multiply exposed uninfected (MEU) patients, and we observed that the éLTNP patients clustered with naive patients, whereas all MEU subjects grouped together. The discriminatory power of miRNAs showed that 21 miRNAs significantly differentiated éLTNP from MEU patients and 23 miRNAs distinguished naive from MEU patients, whereas only 1 miRNA (miR-155) discriminated éLTNP from naive patients. We proposed that miRNA expression may discriminate between HIV-1-infected and -exposed but negative patients. Analysis of miRNAs expression after exposure of healthy CD4(+) T cells to gp120 in vitro confirmed our hypothesis that a miRNA profile could be the result not only of a productive infection but also of the exposure to HIV-1 products that leave a signature in immune cells. The comparison of normalized Dicer and Drosha expression in ex vivo and in vitro condition revealed that these enzymes did not affect the change of miRNA profiles, supporting the existence of a Dicer-independent biogenesis pathway.

Risk of Developing Specific AIDS-Defining Illnesses in Patients Coinfected with HIV and Hepatitis C Virus With or Without Liver Cirrhosis

BACKGROUND There are few data concerning the risk of specific opportunistic diseases in patients with and without hepatitis C virus (HCV) infection. We evaluated the correlation between the occurrence of different AIDS-defining illnesses (ADIs) and chronic HCV infection or HCV-related liver cirrhosis in a large Italian cohort of human immunodeficiency virus (HIV)-infected subjects. METHODS Subjects were stratified into 2 groups: patients without HCV coinfection and with persistently normal aminotransferase levels and patients with HCV coinfection. The patients with HCV coinfection were stratified according to the diagnosis of liver cirrhosis. The incidences of new ADIs were calculated as the number of events per 1000 person-years of follow-up. The rates in the 2 groups were compared using a Poisson regression model adjusted for potential confounders. RESULTS We observed a total of 496 ADIs among 5397 patients with 25,105 person-years of follow-up (50% tested positive for HCV). HCV coinfection was associated with increased risk of developing an ADI (adjusted relative rate [ARR], 2.61; 95% confidence interval [CI], 1.88-3.61), specifically bacterial infection (ARR, 3.15; 95% CI, 1.76-5.67), HIV-related disease (ARR, 2.68; 95% CI, 1.03-6.97), and mycotic disease (ARR, 3.87; 95% CI, 2.28-6.59) but not non-Hodgkin lymphoma (ARR, 0.88; 95% CI, 0.22-3.48). The rate of mycotic infection, bacterial infection, toxoplasmosis, and HIV-related ADI among patients with cirrhosis were significantly higher than that among HIV-monoinfected patients, and the risk was greater than that estimated for HCV antibody-positive patients without cirrhosis. CONCLUSIONS HIV-related bacterial and mycotic infections are strongly associated with positive HCV serostatus and HCV-related cirrhosis. Clinicians should take into account these data when making decisions on initiation of antiretroviral therapy for HCV-coinfected individuals.

Coinfection with HIV-1 and human T-Cell lymphotropic virus type II in intravenous drug users is associated with delayed progression to AIDS

Human T-cell lymphotropic virus (HTLV) type II has spread among intravenous drug users (IDUs), many of whom are coinfected with HIV-1. We have investigated the rate of HTLV-II infection in 3574 Italian IDUs screened for HIV-1, HTLV-I, and HTLV-II from 1986 to the present. HTLV-II proviral load was determined by a real-time polymerase chain reaction specifically designed for tax amplification. The frequency of HTLV-II infection was 6.7% among HIV-1-positive subjects and 1.1% among HIV-1-negative subjects (P < 0.0001). For examination of AIDS progression, a group of 437 HIV-1-monoinfected subjects and another group of 96 HIV-1/HTLV-II-coinfected subjects were monitored. Enrollees were matched at entry by CD4 cell counts and followed for an average of 13 years. HIV-1/HTLV-II coinfection was associated with older age (P < 0.0001) and higher CD4 (P < 0.0001) and CD8 (P < 0.001) cell counts compared with monoinfected IDUs. The number of long-term nonprogressors for AIDS was significantly higher (P < 0.0001) among coinfected patients (13 [13.5%] of 96 patients) than HIV monoinfected patients (5 [1.1%] of 437 patients), showing that HTLV-II exerts a protective role. An increased incidence of liver disease and hepatitis C virus positivity among coinfected IDUs was observed. Five coinfected subjects undergoing antiretroviral therapy showed a significant (P < 0.05) increase in HTLV-II proviral load concomitant to a decrease in HIV-1 viremia, suggesting that the treatment is ineffective against HTLV-II infection.

Second-line chemotherapy in human immunodeficiency virus-related non-Hodgkin's lymphoma : Evidence of activity of a combination of etoposide, mitoxantrone, and prednimustine in relapsed patients

There is very little experience reported in the literature on the treatment of patients with relapsed or resistant human immunodeficiency virus‐related non‐Hodgkins lymphoma (HIV‐NHL). We performed a prospective study to evaluate the feasibility and activity of a second‐line chemotherapy regimen consisting of etoposide, mitoxantrone, and prednimustine (VMP) in this setting.

Decoration of graphene with nickel nanoparticles: study of the interaction with hydrogen

Graphene obtained from thermal exfoliation of graphite oxide was chemically functionalized with nickel nanoparticles (NPs) without exposing the system to oxidizing agents. Its structural, physical and chemical properties have been studied by means of TEM, X-ray photoelectron and Raman spectroscopies, and SQuID magnetometry. The formation of 17 nm super-paramagnetic (SPM) monodispersed Ni NPs was observed. Nitrogen sorption experiments at 77 K yield a Brunauer–Emmet–Teller specific surface area (BET-SSA) of 505 m2 g−1 and helium adsorption at room temperature gives a skeletal density of 2.1 g cm−3. The interaction with atomic hydrogen was investigated by means of Muon Spin Relaxation (μSR) showing a considerable fraction of captured muonium (∼38%), indicative of strong hydrogen–graphene interactions. Hydrogen adsorption has been measured via pressure concentration isotherms demonstrating a maximum of 1.1 mass% of adsorbed hydrogen at 77 K and thus a 51% increased hydrogen adsorption compared to other common carbon based materials.

Dynamics of HIV viral load in blood and semen of patients under HAART: impact of therapy in assisted reproduction procedures.

We examined the efficacy and effect of HAART in HIV-1-infected men confronted with assisted fertilization procedures. We showed that HAART did not always reduce the HIV-1-RNA level in blood and semen compartments, and that a significant upward shift in mitochondrial DNA was observed in spermatozoa from a HAART-treated patient group compared with spermatozoa from HAART-untreated or HIV-1-uninfected groups (P < 0.001). These findings emphasize the negative role of HAART, but not of HIV-1 infection, in determining semen alterations.

Exposure to Abacavir and Biomarkers of Cardiovascular Disease in HIV-1-Infected Patients on Suppressive Antiretroviral Therapy: A Longitudinal Study.

To the Editors: A large observational study found an association between the use of the nucleoside reverse transcriptase inhibitor abacavir and an increase of cardiovascular risk in HIV-1–infected patients. Since then, different studies have reported controversial results: some cohort studies seemed to confirm the observation, whereas other more recent analyses and a meta-analysis seem to contradict this hypothesis. Currently, the major treatment guidelines warrant caution in the prescription of this drug in patients already showing a high cardiovascular risk based on traditional parameters. Nonetheless, a biological mechanism explaining the reasons for this finding has never been elucidated. Despite an initial observation of higher levels of inflammatory markers in a cross-sectional analysis of samples from 2 observational cohorts, subsequent longitudinal studies failed to detect significant associations between the use of abacavir and changes in the levels of cardiovascular risk biomarkers. In this longitudinal observation, we compared groups of patients with different patterns of exposure to abacavir to evaluate the possible effects of the use of this antiretroviral on the plasma levels of several biomarkers associated with cardiovascular risk. From the biological repository of the ICoNA Foundation study (for more details), we collected longitudinal sample pairs from HIV-infected patients aged .18 years, treated with combination antiretroviral therapy and with a stable viral load below 400 copies per milliliter at the time of and between the 2 sampling dates. Patients with hypersensitivity reaction to abacavir, active opportunistic infections in the last year, those with chronic inflammatory diseases or treated with any corticosteroid or anti-inflammatory therapy, pregnant women, and patients with previous myocardial infarction were excluded. The longitudinal sample pairs were classified in 4 different groups according to the timing of their collection as follows: patients starting abacavir (group A); patients continuously receiving abacavir (group B); patients discontinuing abacavir (group C); and patients never exposed to abacavir (group D). In some cases, 3 longitudinal samples were collected from the same patient. There were patients contributing sample pairs to different groups. High sensitivity CRP was measured by nephelometry using an automatic analyzer (ILab 350, Instrumentation Laboratory, Milan, Italy). D-Dimer was evaluated employing a latex particle-enhanced immunoturbidimetric assay (IL ACL9000, Instrumentation Laboratory, Milan, Italy). The other biomarkers were measured in plasma samples by commercially available immunoenzymatic assays: P-selectin, sICAM-1, and sVCAM-1 (Bender MedSystems Europe, Vienna, Austria), IL-6 (R&D System Europe, Abington, United Kingdom), tissue plasminogen activator (t-PA), and plasminogen activator inhibitor (PAI)-1 (American Diagnostica Inc. Gmbh, Pfungstadt, Germany). The detection limits were 2.2 ng/mL for ICAM-1, 1.06 ng/mL for P-selectin, 0.6 ng/mL for VCAM-1, 1.0 ng/mL for t-PA, 1.0 ng/mL for PAI-1, 0.70 pg/mL for IL-6, and 1.6 pg/ml for tumor necrosis factor-alpha. We collected 161 samples from 60 patients. Considering that 1 patient and also 1 single sample could contribute to more than 1 pair, these samples contributed to 86 pairs. The main baseline characteristics of patients according to their current exposure to abacavir and those of patients according to the 4 groups of exposure to the drug are shown in the online Table (see Supplemental Digital Content, http://links.lww.com/QAI/A326). In a first cross-sectional analysis, higher levels of PAI-1 were observed in patients currently exposed versus those not currently exposed to abacavir (+0.18 log10 ng/mL, 95% confidence interval: 0.07 to 0.30, P = 0.002, Wilcoxon test). The difference was larger (+0.31 log) after adjusting for age, gender, duration of HIV RNA suppression, a diagnosis of AIDS before sampling, viral load and CD4 count at sampling, smoking status, lipids, systolic blood pressure, and concomitant use of other antiretrovirals, but it did not reach statistical significance (P = 0.18). No differences were observed in the levels of the other biomarkers between these 2 groups of samples. The longitudinal analysis did not show significant changes of the levels of biomarkers between paired samples within the 4 study groups (not shown). Given the high proportion of IL6 measures below the detection limit, we The Icona Foundation Study is supported by unrestricted educational grants from Abbott, Bristol-Myers-Squibb, Gilead, GlaxoSmithKline, Pfizer, and Janssen-Cilag. A.D.L. received speaker honoraria and fees for attending advisory boards from GlaxoSmithKline, Gilead, Bristol-Myers-Squibb, Boehringer-Ingelheim, Abbott Virology, Tibotec, and Monogram Biosciences. M.C. has been a paid consultant for Merck Sharp and Dohme, Italy, and has been employed by BristolMyers-Squibb, Italy, since May 10, 2010, to February 28, 2011. A.D.M. received speaker honoraria and fees for attending advisory boards from GlaxoSmithKline, Gilead, Bristol-Myers-Squibb, Boehringer-Ingelheim, Abbott Virology, Tibotec. No other member of the Icona Foundation Study has any financial or personal relationships with people or organizations that could inappropriately influence this work, although most members of the group have, at some stage in the past, received funding from a variety of pharmaceutical companies for research, travel grants, speaking engagements or consultancy fees. The funding sources had no role in the study design, conduct or analyses, and were not involved in the decision to submit the article for publication. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (www.jaids.com). The Members of The ICoNA Foundation Study Group are listed in the Appendix I.

HTLV-II does not adversely affect the natural history of HIV-1 infection in intravenous drug users

The influence of the human T cell leukaemia virus type II (HTLV-II) on the natural history of HIV-1 infection in coinfected subjects has not yet been clarified. Weiss et al. [1] reported a higher mortality and Page et al. [2] found a significantly increased risk for the development of AIDS in intravenous drug users (IVDUs) coinfected with HTLV-II and HIV-1,.compared to individuals infected with HIV-1 alone. In contrast, Visconti et al. [3] recently described less immunological impairment and a delayed HIV-1 disease progression in coinfected subjects. In order to address this debated issue, we compared the immunological and clinical outcome of HIV-1 seropositive IVDUs, with and without HTLV-II coinfection. From January 1986 to December 1988, serum samples from a cohort of 437 IVDUs followed in the Drug Dependency Unit of the Hospital of Parma (Italy) have been collected and tested for HIV-1 and HTLV-I/II . The presence of anti-HIV-1 antibodies was determined by commercial enzyme immune assays (ELISA) (Abbott Laboratories, North Chicago, USA) and confirmed by Western blot analysis (Du Pont de Nemours, Milan, Italy). Initially, presence of HTLV-I/II antibodies was determined by agglutination assay (Fujirebio, Tokyo) and ELISA (Diagnostic Biotechnology, Ltd., Singapore). Ant i -HTLV:I/ I I positivity was confirmed by Western blot (Diagnostic Biotechnology, Ltd., Singapore), according to the manufacturer s instructions. To confirm further HTLV infection and to differentiate between HTLV-I and HTLV-II infection, polymerase chain reaction (PCR) was performed on lymphocyte samples of subjects with HTLV positivity using a tax gene primer pair, recognizing both HTLV-I and HTLV-II sequences; specific probes were then used to distinguish the two viruses [4]. Three hundred and sixty six patients tested seropositive for HIV1 antibodies, with an overall seroprevalence of 83.7%. The incidence of anti-HTLV antibodies was 2.05%, with a similar distribution among HIV-1 infected and uninfected subjects (2.1% and 1.4%, respectively). Al l subjects with confirmed HTLV seropositivity showed HTLV-II infection by PCR. Five HTLV-II and HIV-1 coinfected patients (group 1, two men and three women, aged 33:0 _+ 4.4 years; two on antiretroviral therapy for 3.0 + 1.4 years), and 44 with HIV-1 infection alone (group 2, 31 men and 13 women, aged 31.7 _+ 3.8 years; 37 on antiretroviral therapy for 3.5 _+ 1.3 years) with similar CDC entry stage, drug history and serology for other viral infections (cytomegalovirus, herpes simplex, Epstein Barr and hepatitis B viruses) were studied. Clinical and immunological data were derived retrospectively from the individual clinical records of patients of both groups (6.0 _+ 1.8 and 6.0 + 1.0 years of observation, respectively). According to a well-defined protocol used in our department for HIV-1 positive individuals, all patients underwent a clinical and laboratory control at least every 3-4 months. The progression rate from asymptomatic conditions (CDC group II A or B) to persistent generalised lymphadenopathy (group III A or B), AIDS-related complex (group IV A), overt AIDS and death from AIDS was calculated as a progression step. Patients in group 2 showed a faster staging progression (93 steps observed, 184 expected) than those in group 1 (four steps observed, 20 expected; chi-square = 6.747, p <0.01). No statistical difference was found in the cumulative survival between the two groups (Kaplan Meier curves estimating the difference in the progression rate by Cox test) even though the progression rate was lower in patients of group 1 (p = 0.23), Overall evaluation, at 12month intervals, of immunological parameters (testing the parallelism hypothesis by analysis of variance) showed a similar decrease per year in the mean number of total lymphocytes (group 1, r = -0.419 vs. group 2, r = -0.958, p = 0.695) and CD8+ (r = -0.681 vs. r = -0.345, p = 0.120) in the two groups; in contrast, a more rapid decrease of CD4+ mean number (r = -0.142 vs. r = -0.927, p = 0.033) and CD4+/CDs+ ratio (r = 0.829 vs. r = -0.660, p = 0.008) was observed in group 2. Although the limited number of the patients in the group coinfected by HIV-1 and HTLV-II may represent a statistical limit , our findings confirm the results of Visconti et al. [3] suggesting that HTLV-II , in contrast to HTLV-I [5], does not adversely affect the natural history of HIV-1 infection. A slower HIV-1 disease progression has indeed been recorded i n some of our HTLV-II coinfected subjects. The lack of a negative influence of HTLV-II on the clinical outcome of HIV-1 disease might be explained by its tropism for CD8+ [6]; in contrast, HTLV-I, which preferentially infects CD4+ lymphocytes, could transactivate HIV-1 and broaden the spectrum of HIV-1 cellular tropism [7].

Copper on carbon materials: stabilization by nitrogen doping

The applicability of Cu/C catalysts is limited by sintering of Cu leading to deactivation in catalytic reactions. We show that the problem of sintering could be resolved by N-doping of the carbon support. Cu nanocatalysts with 1 at% of metal were synthesized by Cu acetate decomposition on N-free and N-doped (5.7 at% N) mesoporous carbon supports as well as on thermally expanded graphite oxide. Catalytic properties of these samples were compared in hydrogen production from formic acid decomposition. The N-doping leads to a strong interaction of the Cu species with the support providing stabilization of Cu in the form of clusters of less than 5 nm in size and single Cu atoms, which were observed in a significant ratio by atomic resolution HAADF/STEM even after testing the catalyst under harsh conditions of the reaction at 600 K. The mean size of the obtained Cu clusters was by a factor of 7 smaller than that of the particles in the N-free catalyst. The N-doped Cu catalyst possessed good stability in the formic acid decomposition at 478 K for at least 7 h on-stream and a significantly higher catalytic activity than the N-free Cu catalysts. The nature of the strongly interacting Cu species was studied by XPS, XRD and other methods as well as by DFT calculations. The presence of single Cu atoms in the N-doped catalysts should be attributed to their strong coordination by pyridinic nitrogen atoms at the edge of the graphene sheets of the support. We believe that the N-doping of the carbon support will allow expanding the use of Cu/C materials for different applications avoiding sintering and deactivation.