Malignant melanoma in HIV: Epidemiology, pathogenesis, and management.

People affected by immunodeficiency, and especially those infected by HIV, are burdened by a higher risk of developing malignancies. It has been estimated that the incidence of melanoma in HIV-infected people is 2.6-fold higher than in uninfected ones. In this group of patients, melanoma shows a more aggressive phenotype and poorer survival rates compared to HIV-negative people. Standard guidelines of diagnosis and care do not exist yet. Studies suggest high index of suspicion and a low threshold for biopsy in HIV-positive patients regardless of their CD4+ count and the use of standard surgical margins for re-excision procedures. In case of diagnosis of melanoma in HIV-positive patients, a thorough search for metastatic disease is recommended because of the more aggressive course of this cancer in HIV-positive patients. Moreover, to rapidly find out any recurrence or metastatic disease after treatment, these patients need a close follow-up, every 3 months, for the first 2 years and at least twice yearly thereafter. Although surgery remains the main therapeutic option, application of immune checkpoint-based immunotherapy is being studied and seems to be promising. The aim of this review is to present the current knowledge and future options for melanoma diagnosis and treatment in people living with HIV.

Positioning of darunavir/cobicistat-containing antiretroviral regimens in real life: results from a large multicentre observational prospective cohort (SCOLTA).

BACKGROUND: Study aim was to evaluate the safety and durability of darunavir/cobicistat (DRV/c) in a real life setting. METHODS: Multicentre prospective cohort study performed in the context of SCOLTA (Surveillance Cohort Long-Term Toxicity Antiretrovirals). Patients were evaluated at baseline, week 24 and 48. Changes were evaluated using the paired t test or signed rank test. The multivariable analysis was performed using a general linear model, after ranking of not normally distributed variables. RESULTS: A total of 249 patients were included, 72 (29%) were in DRV/c-based dual therapies (DT). Hypercholesterolemia, HC, (total cholesterol (TC) ≥ 200 mg/dL or low density-C (LDL-C) ≥ 130 or statin use) was present in 121 (48.6%) and hypertriglyceridemia, (triglycerides (TG) ≥ 200 mg/dl or fibrate use) in 41 (16.5%) patients. Blood lipid profile did not change significantly in either the global population or patients with HC. After a median observation of 17 months (IQR 13-20), 59 (25.3%) patients discontinued DRV/c, of which 13 were in DT. The durability DT resulted higher than that of triple therapy (log-rank test p = 0.01). Main reasons for stopping DRV/c were simplification (15 patients), adverse events (13 patients), planned discontinuation for treatment initiation with DAA (4 patients), treatment failure (2 patients); death (2 patients), other causes (10 patients). Twenty-six were lost to follow-up. CONCLUSIONS: DRV/c was safe and well tolerated. Dual therapies showed a better profile of tolerability and a longer durability compared to triple therapies.

Outbreak of Brucella melitensis infection in Eastern Sicily: risk factors, clinical characteristics and complication rate.

Brucellosis is one of the most common zoonoses in the world, especially in Southern Italy, where many cases are still recorded every year. 128 cases of brucellosis were observed in Messina (Sicily) in 2016, representing a tenfold increase in the number of cases of brucellosis expected. The aim of this multicenter retrospective study was to analyze clinical and microbiological aspects of a brucellosis outbreak in the province of Messina in 2016, the incidence of its complications and the treatment combinations applied. The principal transmission route was through the ingestion of unpasteurized fresh cheese. The mean latency period between the onset of the symptoms and diagnosis was 35.58±42.75 days. A late diagnosis increases the risk of developing complications. Drug-resistant strains of B. melitensis to Trimethoprim/ Sulfamethoxazole and Ciprofloxacin were found in blood cultures of 58.4% patients. Brucellosis is still present in Sicily. A diagnostic delay predisposes to complications requiring prolonged therapies. The finding of Brucella melitensis strains resistant to the most widespread treatments is worrisome and needs further investigation. Moreover, the use of alternative combination antibiotic therapy is recommended.

Outbreak of Brucella melitensis infection in Eastern Sicily: risk factors, clinical characteristics and complication rate.

Brucellosis is one of the most common zoonoses in the world, especially in Southern Italy, where many cases are still recorded every year. 128 cases of brucellosis were observed in Messina (Sicily) in 2016, representing a tenfold increase in the number of cases of brucellosis expected. The aim of this multicenter retrospective study was to analyze clinical and microbiological aspects of a brucellosis outbreak in the province of Messina in 2016, the incidence of its complications and the treatment combinations applied. The principal transmission route was through the ingestion of unpasteurized fresh cheese. The mean latency period between the onset of the symptoms and diagnosis was 35.58 ± 42.75 days. A late diagnosis increases the risk of developing complications. Drug-resistant strains of B. melitensis to Trimethoprim/Sulfamethoxazole and Ciprofloxacin were found in blood cultures of 58.4% patients. Brucellosis is still present in Sicily. A diagnostic delay predisposes to complications requiring prolonged therapies. The finding of Brucella melitensis strains resistant to the most widespread treatments is worrisome and needs further investigation. Moreover, the use of alternative combination antibiotic therapy is recommended.

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. Among all the molecules that at present are under investigation, entry and fusion inhibitors pose an interesting class owing to their peculiar characteristics, including prevention of entry of the virus into the human cells. In this study, we reviewed articles, clinical trials, and conference communications about all the drugs under investigation belonging to the class of entry and fusion inhibitors that are at least in phase I clinical trials.

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. HIV-positive patients were on cART for at least one year. Urine and blood samples were collected. Various factors were analyzed including body mass index (BMI), smoking, and presence/treatment for comorbidities such as diabetes. The estimated glomerular filtration rate was calculated by using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Plasma samples obtained were stored and used to measure sCD14 and ANGPTL2 levels. Data were presented as mean (± standard deviation) or median (interquartile range) for continuous variables. Categorical variables were expressed as number (%). Variables were compared using Student's t-test, Mann-Whitney test, or χ2 test. The results showed an independent negative association between plasma ANGPTL2 and CKD-EPI values. Further prospective studies on larger cohorts are needed to evaluate the pathogenetic role of ANGPTL2 as well as its use as a diagnostic marker of renal dysfunction.