Direct-acting antivirals in hepatitis C virus (HCV)-infected and HCV/HIV-coinfected patients: real-life safety and efficacy.

OBJECTIVES: Clinical trials of all-oral direct-acting antivirals (DAAs) for chronic hepatitis C virus (HCV) infection reported high response rates in HCV/HIV coinfection, similar to those obtained in HCV monoinfection. We evaluated the safety and efficacy of these regimens in a clinical practice setting. METHODS: In this prospective observational study, all the HCV-monoinfected and HCV/HIV-coinfected patients undergoing HCV treatment with all-oral DAA regimens in a routine clinical setting from December 2014 to December 2015 were included in the analysis. Sustained virological response 12 weeks after the end of therapy (SVR12) and reported adverse events (AEs) were evaluated. Resistance-associated variants (RAVs) were analysed in a subgroup of patients at baseline and at the time of viral rebound in those with virological failure. RESULTS: One-hundred and nine patients (51 HCV-infected and 58 HCV/HIV-coinfected) were enrolled in the study. Sixty per cent had cirrhosis and 52% were pegylated interferon and ribavirin (pegIFN/RBV)-experienced. Thirty-six per cent received ombitasvir + paritaprevir/ritonavir + dasabuvir, 25% sofosbuvir + daclatasvir, 16% sofosbuvir + simeprevir, 17% sofosbuvir + ribavirin and 6% sofosbuvir + ledipasvir; ribavirin was used in 57% of subjects. The SVR12 rate was 91% and 96% in HIV-infected and uninfected patients, respectively (P = 0.44). The 4-week HCV viral decline was similar in the two groups. RAVs were found at baseline in 23 of 49 patients and did not affect SVR12. No predictors of SVR12 were identified in our cohort. CONCLUSIONS: Treatment with all-oral DAA combinations of patients infected with HCV and with HCV/HIV under real-life conditions led to high and similar rates of SVR12. Moreover, the historical factors associated with a sustained virological response to pegIFN/RBV were not predictive of the response to all-oral DAAs.

Nonclassical radiation from thermal cavities in the ultrastrong coupling regime.

Thermal or chaotic light sources emit radiation characterized by a slightly enhanced probability of emitting photons in bunches, described by a zero-delay second-order correlation function g((2))(0)=2. Here we explore photon-coincidence counting statistics of thermal cavities in the ultrastrong coupling regime, where the atom-cavity coupling rate becomes comparable to the cavity resonance frequency. We find that, depending on the system temperature and coupling rate, thermal photons escaping the cavity can display very different statistical behaviors, characterized by second-order correlation functions approaching zero or greatly exceeding two.

Spontaneous conversion from virtual to real photons in the ultrastrong-coupling regime.

We show that a spontaneous release of virtual photon pairs can occur in a quantum optical system in the ultrastrong coupling regime. In this regime, which is attracting interest both in semiconductor and superconducting systems, the light-matter coupling rate Ω(R) becomes comparable to the bare resonance frequency of photons ω(0). In contrast to the dynamical Casimir effect and other pair creation mechanisms, this phenomenon does not require external forces or time dependent parameters in the Hamiltonian.

Photon blockade in the ultrastrong coupling regime.

We explore photon coincidence counting statistics in the ultrastrong coupling regime, where the atom-cavity coupling rate becomes comparable to the cavity resonance frequency. In this regime, usual normal order correlation functions fail to describe the output photon statistics. By expressing the electric-field operator in the cavity-emitter dressed basis, we are able to propose correlation functions that are valid for arbitrary degrees of light-matter interaction. Our results show that the standard photon blockade scenario is significantly modified for ultrastrong coupling. We observe parametric processes even for two-level emitters and temporal oscillations of intensity correlation functions at a frequency given by the ultrastrong photon emitter coupling. These effects can be traced back to the presence of two-photon cascade decays induced by counterrotating interaction terms.

Clinical presentation and outcome of squamous cell carcinoma of the anus in HIV-infected patients in the HAART-era: a GICAT experience.

INTRODUCTION: Squamous cell carcinoma of the anus (SCCA) is a relatively uncommon cancer. In the HIV-positive patients the introduction of the highly active antiretroviral therapy (HAART) did not change the incidence of SCCA. BACKGROUND AND OBJECTIVES: This paper describes the Italian Cooperative Group on AIDS and Tumours (GICAT) experience on HIV-positive patients with SCCA. The purposes of this retrospective study were: first to describe the clinical presentation and outcome of HIV-positive patients with SCCA, second to compare them with the ones reported in the literature. PATIENTS AND METHODS: Between July 2000 and March 2010 we retrospectively collected epidemiological, clinical and survival data from 65 patients with SCCA in HIV infection enrolled within the GICAT. RESULTS: Fifty-three (81.5%) patients were male. The majority of patients (40%) were homosexual Forty-three patients (66.1%) were diagnosed with HIV before 1996. Thirty-five patients (54%) had CD4-positive cells count > 200 / mm3 and 28 patients (43%) had viral load > 50 cp / ml at the time of SCCA diagnosis. The median time difference between HIV and SCCA diagnosis was 120 months (range 10-282 months). Sixty-one patients (96.8%) received HAART at SCCA diagnosis. Fifty-two patients (80%) had performance status (PS) 0-1 at the time of SCCA diagnosis. Twenty-seven patients (41.5%) underwent surgery with curative intent. Thirty-five patients (53.9%) were given combined modality therapy (CMT) consisting of pelvic radiotherapy with concurrent chemotherapy. No grade 3/4 haematological or extra-haematological effects were observed in our patients. CONCLUSIONS: In summary, despite the retrospective nature of analysis, the absence of patient strict criteria of inclusion/exclusion, our data on HIV-positive patients with SCCA, compared both to general population and to small reports on HIV-positive patients present in the literature, are promising.

Test of the all-optical control of wave-particle duality of cavity photons by ordinary photodetection.

The principle of complementarity refers to the ability of quantum entities to behave as particles or waves under different experimental conditions. We present a proposal for the experimental observation of the ultrafast all-optical control of the wave-particle duality of light. The device is constituted by a three-level quantum emitter strongly coupled to a microcavity (MC) and can be realized by exploiting a great variety of systems, ranging from atomic physics and semiconductor quantum dots to intersubband polaritons and Cooper pair boxes. The wavelike or particlelike behavior of MC photons can be probed by simply measuring the cavity output photon rate after excitation with pairs of phase-locked weak pulses with precise arrival times.

All optical switch of vacuum Rabi oscillations: the ultrafast quantum eraser.

We study the all-optical time control of the strong coupling between a single cascade three-level quantum emitter and a microcavity. We find that only specific arrival times of the control pulses succeed in switching off the Rabi oscillations. Depending on the arrival times of control pulses, a variety of exotic nonadiabatic cavity quantum electrodynamics effects can be observed. We show that control pulses with specific arrival times, performing which-path and quantum-eraser operations, are able to suddenly switch-off and on first-order coherence of cavity photons, without affecting their strong coupling population dynamics.

Quantum plasmonics with quantum dot-metal nanoparticle molecules: influence of the Fano effect on photon statistics.

We study theoretically the quantum optical properties of hybrid molecules composed of an individual quantum dot and a metallic nanoparticle. We calculate the resonance fluorescence of this composite system. Its incoherent part, arising from nonlinear quantum processes, is enhanced by more than 2 orders of magnitude as compared to that of the dot alone. The coupling between the two systems gives rise to a Fano interference effect which strongly influences the quantum statistical properties of the scattered photons: a small frequency shift of the incident light field may cause changes in the intensity correlation function of the scattered field of orders of magnitude. The system opens a good perspective for applications in active metamaterials and ultracompact single-photon devices.

Ultrastrong coupling probed by Coherent Population Transfer.

Light-matter interaction, and the understanding of the fundamental physics behind, is the scenario of emerging quantum technologies. Solid state devices allow the exploration of new regimes where ultrastrong coupling strengths are comparable to subsystem energies, and new exotic phenomena like quantum phase transitions and ground-state entanglement occur. While experiments so far provided only spectroscopic evidence of ultrastrong coupling, we propose a new dynamical protocol for detecting virtual photon pairs in the dressed eigenstates. This is the fingerprint of the violated conservation of the number of excitations, which heralds the symmetry broken by ultrastrong coupling. We show that in flux-based superconducting architectures this photon production channel can be coherently amplified by Stimulated Raman Adiabatic Passage, providing a unique tool for an unambiguous dynamical detection of ultrastrong coupling in present day hardware. This protocol could be a benchmark for control of the dynamics of ultrastrong coupling architectures, in view of applications to quantum information and microwave quantum photonics.

Chagas disease knocks on our door: a cross-sectional study among Latin American immigrants in Milan, Italy.

OBJECTIVES: We aimed to assess the prevalence and risk factors for Chagas disease (CD) in Latin American immigrants and to evaluate the accuracy of diagnostic tests. Moreover, we offered to all positive subjects a complete free-of-charge clinical/instrumental evaluation as well as benznidazole treatment in order to stage the disease and verify drug tolerability. METHODS: A cross-sectional survey of CD among Latin Americans living in Milan and its metropolitan area was conducted between July 2013 and July 2014. Blood samples were tested for serologic evidence of CD together with a questionnaire covering demographic and clinical-epidemiological information. RESULTS: Forty-eight (9.6%) of the 501 tested subjects were conclusively diagnosed as having CD. The highest prevalence of CD was among those from Bolivia (43/169, 25.4%) and El Salvador (4/68, 5.9%). Older age (adjusted odds ratio (aOR)] 1.05, p =0.004), a Bolivian origin (aOR 8.80; p =0.003), being born in the department of Santa Cruz (aOR 3.72, p =0.047), having lived in mud houses (aOR 2.68; p =0.019), and having an affected relative (aOR 12.77, p =0.001) were independently associated with CD. The ARCHITECT Chagas test showed the highest sensitivity (100%) and specificity (99.8%). Twenty-nine of the subjects with CD (60.4%) underwent disease staging, 10 of whom (35.7%) showed cardiac and/or digestive involvement. Benznidazole treatment was associated with high frequency of adverse reactions (19/27, 70.4%) and permanent discontinuation (8/27, 29.6%). CONCLUSIONS: CD is highly prevalent among Bolivians and Salvadorans living in Milan. Regions with a large Latin American immigrant population should implement programmes of active detection and treatment.

Laser light triggered smart release of silibinin from a PEGylated-PLGA gold nanocomposite.

In this work a new remotely-triggered drug delivery system based on PEG-PLGA_Au nanocomposite is proposed. Due to the optical properties of gold nanoparticles (Au NPs), the nanovector allows on-demand control of the dose, the timing and the duration of the drug release, upon irradiation with red laser light. The Au NPs are synthesized by laser ablation and subsequently embedded into the PEG-PLGA copolymer via a modified emulsion-diffusion method, devised in such a way that both Au NPs and silibinin (SLB), a flavonolignan with promising anti-neoplastic effects, can be co-loaded into the polymeric system in a single step procedure. A combination of analytical techniques including nuclear magnetic resonance (NMR), static and dynamic light scattering (SLS, DLS), gel permeation chromatography (GPC), thermogravimetric analysis (TGA), X-ray photoelectron spectroscopy (XPS), infrared (FTIR) spectroscopy and scanning/transmission electron microscopies (SEM/STEM/TEM), have been used to study the structural and morphological properties of the nanocomposite. The loading efficiency and the drug content, evaluated by UV-vis absorption optical spectroscopy, are 89% and 8.8%, respectively. Upon laser irradiation the system releases the encapsulated drug with a higher efficiency (∼10%) than that without irradiation. This behaviour indicates that our nanoplatform is responsive to light and it could be considered a promising new type of light-activated drug delivery carrier applicable to the biomedical field.

Soluble interleukin-2 receptor decrease in the sera of HIV-infected patients treated with zidovudine.

Laboratory parameters which are modified following administration of zidovudine are becoming increasingly useful in monitoring the efficacy of treatment of early stages of HIV-1 infection. The serum levels of soluble interleukin (sILR)-2 receptor, which have been reported to increase early in HIV-1 infection, were found to be significantly lower in 24 patients being treated with zidovudine than in 69 patients who were not treated, 28 of whom had CD4+ counts greater than 400 x 10(6)/l, and 41 less than 400 x 10(6)/l, respectively (P less than 0.0001). A prospective study group of 33 subjects treated with zidovudine demonstrated a decrease in sIL-2R during therapy (base values 2113 +/- 1131 versus 1444 +/- 728 after 90 days of therapy; P less than 0.0007). The reduction of sIL-2R was greater in those subjects were p24 antigen became negative during treatment. sIL-2R therefore seems to be a useful tool in the monitoring of therapy with zidovudine.

High frequency of non-Hodgkin's lymphoma in patients with HIV-associated Kaposi's sarcoma.

OBJECTIVE: To evaluate, with the support of autopsy findings, the frequency of non-Hodgkin's lymphoma (NHL) among patients with AIDS-associated Kaposi's sarcoma (KS) in comparison with that of AIDS patients with other AIDS-defining diseases. METHODS: The study involved 363 consecutive patients with AIDS who were cared for and died at the Clinic of Infectious Diseases in Milan between May 1984 and December 1992. Clinical records and autopsy data of all of the patients were retrospectively reviewed. Kaplan-Meier product-limit estimates of the time to the development of NHL were calculated for all patients and by specific subgroups. Cox proportional hazards analyses were made to determine the factors associated with the development of NHL. RESULTS: In the majority of cases (82%), KS was diagnosed during life, whereas NHL was diagnosed before death in only 41.6% of cases. Taking the autopsy data into account, the cumulative incidence of the two tumours was 16.8% for KS and 16.5% for NHL. Among the 61 patients in whom KS was the index disease of AIDS, 16 also developed NHL. The probability of developing NHL was significantly higher in patients with KS at AIDS diagnosis than in patients with Pneumocystis carinii pneumonia (PCP), oesophageal candidiasis or other AIDS-related diseases (P = 0.004). Multivariate analysis of the factors associated with the development of NHL (such as sex, age, risk factors, AIDS-defining diseases and CD4+ cell counts) showed that the patients with KS as the index disease of AIDS had a 5.3-fold higher risk of developing NHL than the patients with PCP as the primary manifestation of AIDS. CONCLUSIONS: Our results confirm the higher incidence of malignant lymphoma in patients with AIDS-KS than in patients with other AIDS-related diseases. The importance of autopsy in assessing these data is underlined by the high percentage of NHL diagnosed only after death. These observations may support the hypothesis of a common aetiological agent, or of a common pathway, for the two neoplasms.

Homozygous delta 32 deletion of the CCR-5 chemokine receptor gene in an HIV-1-infected patient.

BACKGROUND: Recent research has found that entry of non-syncytium-inducing (NSI), monocyte-macrophage-tropic HIV-1 isolates requires binding to both CD4 and CCR5 receptors, and that delta 32/delta 32 homozygous individuals are protected against infection. OBJECTIVE: To analyse the polymorphism of CCR-5 gene in HIV-1-infected and uninfected subjects. DESIGN AND METHODS: CCR-5 sequences were amplified by polymerase chain reaction (PCR) from DNA of peripheral blood mononuclear cells. Samples from 152 HIV-1-infected subjects and 122 uninfected controls were tested for the detection of the 32 base-pair deletion. HIV-1 phenotype was determined by viral isolation and MT-2 evaluation. RESULTS: The wild-type/delta 32 heterozygous and delta 32/delta 32 homozygous conditions were represented in 10.7 and 0.8% of healthy controls and in 9.8 and 0.7% of HIV-1-infected subjects, respectively. Of note, the delta 32/delta 32 deletion of the CCR-5 gene was detected by PCR and sequencing confirmed in a patient with progressive infection harbouring a clade B virus with SI phenotype. CONCLUSIONS: delta 32/delta 32 homozygosity for the CCR-5 gene does not confer absolute protection against HIV-1 infection, suggesting that either macrophage-tropic viral strains could use coreceptors other than CCR-5 or infect independently of the presence of a functional CCR-5 coreceptor. Alternatively, primary infection sustained by T-cell-tropic isolates, although exceptional, may occur.

Redistribution of body fat in HIV-infected women undergoing combined antiretroviral therapy.

OBJECTIVES: To investigate the prevalence, metabolic features and risk factors of a particular pattern of fat redistribution (FR), characterized by a progressive enlargement of breast and abdominal girth associated with a wasting of the lower limbs, observed in HIV-infected women treated with combined antiretroviral (ARV) therapy. DESIGN: Cross-sectional study. SETTING: Outpatients attending the Institute of Infectious Diseases, University of Milan, Milan, Italy. PATIENTS AND METHODS: HIV-infected women treated with two or more ARV drugs, observed between December 1997 and February 1998. FR was confirmed by means of a physical examination and dual-energy X-ray absorptiometry (DEXA). The metabolic and endocrinological measurements in patients with FR were compared with those in FR-free women. RESULTS: FR was observed in 32 out of 306 women (10.5%). DEXA revealed more trunk fat (P < 0.01) and less leg fat (P < 0.001) in the patients with FR than in the matched controls. There were no significant differences in laboratory test results between the two groups. All of the FR patients were taking lamivudine-containing regimens; 20 of them were also taking a protease inhibitor (PI). The association of FR with lamivudine-including regimens was statistically significant (P = 0.017). Among the patients taking lamivudine, the risk associated with treatments including PI was 1.8 (95% CI 0.8-3.8, P = 0.12). A total duration of ARV therapy of more than 1000 days was associated with a greater risk of developing FR (OR 10.8; 95% CI 1.4-80.5; P = 0.0207). Stepwise logistic regression analyses indicated that prolonged ARV therapy and a viral load of more than 10000 copies per ml at the beginning of the last ARV regimen were the only variables that significantly and independently correlated with the risk of FR. CONCLUSIONS: The observed body modifications are caused by a redistribution of body fat without fat loss that is apparently not associated with hyperlipidemia, altered glucose metabolism or other endocrinological disorders. The development of FR in patients receiving only reverse transcriptase (RT) inhibitors suggests the presence of a PI-independent mechanism that deserves further investigation.

Benoxaprofen kinetics in renal impairment.

To establish therapeutic guidelines, benoxaprofen kinetics were examined in 26 adult subjects with normal and decreased renal function. Mean peak plasma concentrations after a single 600-mg dose ranged from 58 to 72 mg/l, independent of renal function. Elimination half-life and benoxaprofen plasma clearance correlated with creatinine clearance. Hemodialysis did not remove benoxaprofen from plasma. A dosage nomogram was derived from which a dose one half of the normal maintenance dose was suggested for patients with severe renal failure.

Persisting HIV-1 replication triggered by acute hepatitis A virus infection.

We report the case of two patients in whom acute hepatitis A was associated with a marked and prolonged increase in human immunodeficiency virus type 1 (HIV-1) viral load. Although in one patient the rise in HIV-1 RNA might also have been related to the interruption of antiretroviral therapy, we also observed a similar pattern in the other patient who had a stable undetectable plasma viraemia prior to acute hepatitis and never received treatment with anti-retrovirals. Our observation supports the hypothesis that immune activation that is induced by acute hepatitis A virus (HAV) infection may trigger HIV-1 replication. This highlights the importance of maintaining antiretroviral therapy throughout the acute phase of hepatitis A and of preventing HAV infection through active immunization.

Role of brain biopsy in the management of focal brain lesions in HIV-infected patients. Gruppo Italiano Cooperativo AIDS & Tumori.

In this multicenter, retrospective study of 160 brain biopsies in the assessment of HIV-related focal brain lesions, diagnostic sensitivity was acceptable (87%), but the procedure carried considerable morbidity (7.5%) and mortality (3.1%). Moreover, it is not always possible to initiate the changes in therapy indicated by the results, and overall survival remains poor, with a median of 2 months. Criteria for brain biopsy for the diagnosis of focal brain lesions should be redefined to include selected patients for whom a less invasive approach does not yield a definitive diagnosis.

Pseudolymphoma of the lung in a patient with systemic lupus erythematosus.

A 47 year old woman with systemic lupus erythematosus was found to have asymptomatic pulmonary nodules. Histologically they represented benign reactive lymphoreticular hyperplasia compatible with the diagnosis of pseudolymphoma. Immunofluorescence and electron microscopy demonstrated immunoreactants and electron-dense deposits in the alveolar and vascular walls, suggesting that an immune complex mechanism may be involved in this case.

A quantitative evaluation of rheumatoid arthritic activity with Tc-99m HEDP.

In an attempt to develop a quantitative method of evaluating rheumatoid arthritic activity, Tc-99m HEDP joint uptake values and joint-to-bone ratios were studied in ten adult rheumatoid arthritic patients and 17 nonarthritic patients. A joint-to-bone activity ratio of 1.8 at the fourth hour after injection (RA Index) discriminated clinically active rheumatoid arthritic joints from control joints with 95% accuracy. Serial studies on five patients during drug trial demonstrated a positive correlation between RA Index and the clinical manifestations of rheumatoid arthritic activity. The RA Index may be a useful quantitative parameter for evaluation of rheumatoid arthritic activity following therapy.