Pharmacological approaches to promote cell death of latent HIV reservoirs.

Purpose Of Review: HIV requires lifelong antiviral treatment due to the persistence of a reservoir of latently infected cells. Multiple strategies have been pursued to promote the death of infected cells.

Recent Findings: Several groups have focused on multipronged approaches to induce apoptosis of infected cells.

Persistence of an intact HIV reservoir in phenotypically naive T cells.

Despite the efficacy of antiretroviral therapy (ART), HIV persists in a latent form and remains a hurdle to eradication. CD4+ T lymphocytes harbor the majority of the HIV reservoir, but the role of individual subsets remains unclear. CD4+ T cells were sorted into central, transitional, effector memory, and naive T cells.

Next-Generation Sequencing in a Direct Model of HIV Infection Reveals Important Parallels to and Differences from Reservoir Dynamics.

Next-generation sequencing (NGS) represents a powerful tool to unravel the genetic make-up of the HIV reservoir, but limited data exist on its use Moreover, most NGS studies do not separate integrated from unintegrated DNA, even though selection pressures on these two forms should be distinct. We reasoned we could use NGS to compare the infection of resting and activated CD4 T cells to address how the metabolic state affects reservoir formation and dynamics. To address these questions, we obtained HIV sequences 2, 4, and 8 days after NL4-3 infection of metabolically activated and quiescent CD4 T cells (cultured with 2 ng/ml interleukin-7).

Longitudinal HIV sequencing reveals reservoir expression leading to decay which is obscured by clonal expansion.

After initiating antiretroviral therapy (ART), a rapid decline in HIV viral load is followed by a long period of undetectable viremia. Viral outgrowth assay suggests the reservoir continues to decline slowly. Here, we use full-length sequencing to longitudinally study the proviral landscape of four subjects on ART to investigate the selective pressures influencing the dynamics of the treatment-resistant HIV reservoir.

Circulating angiopoietin-like protein 2 levels are associated with decreased renal function in HIV subjects on cART: A potential marker of kidney disease.

Chronic kidney disease (CKD) is an important cause of morbidity and mortality in HIV-infected individuals, even in the antiretroviral therapy (ART) era. Inflammatory cytokines and adipokines have been suggested to play a role in the development of CKD. The aim of the present study was to examine the circulating levels of a novel proinflammatory cytokine, angiopoietin-like protein 2 (ANGPTL2), in a cohort of 72 HIV-positive subjects on ART.

Investigational drugs in HIV: Pros and cons of entry and fusion inhibitors (Review).

Despite the profound changes and improvements reached in the field of HIV treatment, tolerability and adherence to highly active antiretroviral therapy remains a challenge. Furthermore, multi-experienced patients could take advantage of drugs with different mechanisms of action to combat the spread of resistance to actual therapy. For these reasons identification of new HIV drugs is crucial.

HIV-associated psoriasis: Epidemiology, pathogenesis, and management.

People living with HIV (PLWH) are affected by a higher incidence skin disorders, which are often associated with high morbidity and mortality. In particular, psoriasis affects PLWH severely and for a longer time than the general population. Human immunodeficiency virus (HIV) infection is characterized by a progressive decrease in CD4 T-cell count, and it could seem paradoxical that psoriasis exacerbations are more frequent in this subset of patients than the general population, even though it is commonly observed at any stage of infection.

Head and neck squamous cell carcinoma and its correlation with human papillomavirus in people living with HIV: a systematic review.

Over the last 20 years we assisted to an increase in the mean age of People Living with HIV and their comorbidities. Especially, there was an increase in Human Papillomavirus-related head and neck squamous cell carcinomas. Despite their increasing incidence in HIV-positive people, mechanisms that lead to their development and progression are only partially understood.

Measuring integrated HIV DNA ex vivo and in vitro provides insights about how reservoirs are formed and maintained.

The identification of the most appropriate marker to measure reservoir size has been a great challenge for the HIV field. Quantitative viral outgrowth assay (QVOA), the reference standard to quantify the amount of replication-competent virus, has several limitations, as it is laborious, expensive, and unable to robustly reactivate every single integrated provirus. PCR-based assays have been developed as an easier, cheaper and less error-prone alternative to QVOA, but also have limitations.

Monitoring Integration over Time Supports a Role for Cytotoxic T Lymphocytes and Ongoing Replication as Determinants of Reservoir Size.

Unlabelled: The dynamics of HIV reservoir accumulation off antiretroviral therapy (ART) is underexplored. Levels of integrated HIV DNA in peripheral blood mononuclear cells (PBMCs) were longitudinally monitored before and after antiviral therapy. HIV integration increased over time in both elite controllers (ECs; n = 8) and noncontrollers (NCs; n = 6) before ART, whereas integration remained stable in patients on ART (n = 4).

Baseline CD4/CD8 T-Cell Ratio Predicts Prompt Immune Restoration Upon cART Initiation.

Introduction: The reversal of CD4/CD8 ratio is considered an independent predictor of death in the general population, where the ratio physiologically decreases with aging. Despite effective cART, CD4/CD8 normalization does not always occur in HIV-positive subjects. In the setting of HIV, low CD4/CD8 T-cell ratio correlates with immune activation and non-AIDS events.

Diagnostic and therapeutic management of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is an increasing health problem, representing the second cause of cancer-related mortality worldwide. The major risk factor for HCC is cirrhosis. In developing countries, viral hepatitis represent the major risk factor, whereas in developed countries, the epidemic of obesity, diabetes and nonalcoholic steatohepatitis contribute to the observed increase in HCC incidence.

Heel quantitative ultrasound in HIV-infected patients: a cross-sectional study.

Purpose: HIV infection has been associated with increased risk of osteoporosis and fragility fractures. Dual-energy X-ray absorptiometry (DXA) is the reference standard to assess bone mineral density (BMD); however, it is not easily accessible in several settings. Heel Quantitative ultrasound (QUS) is a radiation-free, easy-to-perform technique, which may help reducing the need for DXA.

Epstein-barr virus- and Kaposi sarcoma-associated herpesvirus-related malignancies in the setting of human immunodeficiency virus infection.

The human gammaherpesvirus family includes Epstein-Barr virus (EBV) and human herpesvirus (HHV)-8, also known as Kaposi sarcoma-associated herpesvirus (KSHV). In human immunodeficiency virus (HIV)-infected patients, both EBV and KSHV have been implicated in the development of a wide range of tumors. KSHV-associated diseases include Kaposi sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman disease (MCD).

Optimal duration of antimicrobial therapy in ventilator-associated pneumonia: What is the role for procalcitonin?

Hospital-acquired pneumonia (HAP) is the major cause of hospital-acquired infections in critically ill patients. Up to 90% of intensive care unit episodes of HAP occur in mechanically ventilated patients, who may develop what is termed ventilator-associated pneumonia (VAP). An appropriate duration of antimicrobial therapy is crucial in the management of HAP: on the one hand, delay in administration of proper therapy has been associated with an increased risk of treatment failure and mortality; on the other hand, unnecessary prolongation of antimicrobial treatment may favour the emergence of multidrug-resistant bacteria and increase healthcare costs.

Is there enough evidence to use bisphosphonates in HIV-infected patients? A systematic review and meta-analysis.

An increased prevalence of osteopenia and osteoporosis has been observed in HIV-infected cohorts. We investigated the effect of bisphosphonates on bone mineral density in adults with HIV infection. Outcomes of interest were bone mineral density changes measured by dual-energy X-ray absorptiometry at the lumbar spine, femoral neck, and total hip, and adverse events.

A measles outbreak in Catania, Sicily: the importance of high vaccination coverage and early notification of cases for health and economic reasons.

Measles is a paediatric exanthematous disease. Even though vaccination has dramatically reduced measles morbidity and mortality, outbreaks still occur due to insufficient vaccination coverage and importation of the virus from endemic regions. Although child vaccination coverage in Italy has been broadened (from 74% in 2000 to 90.

Atypical Presentation of PKDL due to Leishmania infantum in an HIV-Infected Patient with Relapsing Visceral Leishmaniasis.

We describe the case of an Italian patient with HIV infection who developed an atypical rash resembling post-kala-azar dermal leishmaniasis (PKDL) when receiving liposomal Amphotericin B (L-AMB) for secondary prophylaxis of visceral leishmaniasis (VL). At the time of PKDL appearance, the patient was virologically suppressed but had failed to restore an adequate CD4+ T-cell count. Histology of skin lesions revealed the presence of a granulomatous infiltrate, with lymphocytes, plasma cells, and macrophages, most of which contained Leishmania amastigotes.

A new sampling method for spleen stiffness measurement based on quantitative acoustic radiation force impulse elastography for noninvasive assessment of esophageal varices in newly diagnosed HCV-related cirrhosis.

In our study, we evaluated the feasibility of a new sampling method for splenic stiffness (SS) measurement by Quantitative Acoustic Radiation Force Impulse Elastography (Virtual Touch Tissue Quantification (VTTQ)).We measured SS in 54 patients with HCV-related cirrhosis of whom 28 with esophageal varices (EV), 27 with Chronic Hepatitis C (CHC) F1-F3, and 63 healthy controls. VTTQ-SS was significantly higher among cirrhotic patients with EV (3.

High prevalence of parotideal abnormalities among HCV infected patients.

Several salivary diseases, such as Sjogren syndrome (SS), chronic lymphocytic sialadenitis and parotid non-Hodgkin's lymphoma, may occur in the setting of HCV infection. Our aim was to evaluate the prevalence of parotid abnormalities in a cohort of 310 patients with chronic hepatitis C (CHC) attending the Unit of Infectious Diseases of the Garibaldi Nesima Hospital of Catania. Our control group consisted of 188 patients with chronic HBV infection.

Duration of antimicrobial therapy in community acquired pneumonia: less is more.

Community acquired pneumonia (CAP) represents the most common cause of infection-related morbidity and mortality worldwide. Appropriate treatment of CAP is challenging and sometimes limited by the availability to obtain rapid and timely identification of the etiologic agent in order to initiate or deescalate the correct antimicrobial therapy. As a consequence, prescribers frequently select empiric antimicrobial therapy using clinical judgment, local patterns of antimicrobial resistance, and, sometimes, individual patient expectations.

Neurocysticercosis in a 23-year-old Chinese man.

Patient: Male, 23 FINAL DIAGNOSIS: Neurocysticerosis Symptoms: Diplopia • fever • headache • insomnia • neck stiffness • vomiting

Medication: Albendazole Clinical Procedure: - Specialty: Neurology.

Objective: Challenging differential diagnosis.

Background: Neurocysticercosis is a brain infection caused by the larval stage of the tapeworm Taenia (T.

Rheumatoid arthritis following PEG-interferon-alfa-2a plus ribavirin treatment for chronic hepatitis C: a case report and review of the literature.

Background: The combination of Pegylated Interferon-alpha (PEG-IFN-α) and ribavirin is the current standard of care for the treatment of HCV infection. Unfortunately, IFN-α may lead to the induction or exacerbation of autoimmune diseases, such as psoriasis, thyroiditis, systemic lupus erythematosus and, rarely, rheumatoid arthritis (RA).

Case Presentation: We report the case of a man affected with chronic hepatitis C (CHC) due to HCV genotype 3a infection, who developed RA after a complete course of PEG-IFN-α and ribavirin.

The complexity of aging: cancer risk among elderly people and infectious risk among those with cancer.

Aging is associated with a reduced capability of the immune system to adequately respond to pathogens and to prevent tumor formation. As a consequence of immunosenescence, older people have a higher risk to develop infections as well as cancer. In addition, cancer itself may expose old patients to infections, including opportunistic infections, i.