Predicting Factors of Plasma HIV RNA Undetectability after Switching to Co-Formulated Bictegravir, Emtricitabine, and Tenofovir Alafenamide in Experienced HIV-1 Patients: A Multicenter Study.

Switching to bictegravir, emtricitabine, and tenofovir alafenamide (BIC/FTC/TAF) from other antiretroviral regimens is safe and effective for virologically suppressed people living with HIV (PLWH). The term virological suppression includes both low but detectable HIV viremia and undetectable HIV viremia, and the latter is possibly associated with a lower immune activation state. Herein, we describe a 24-month follow-up of experienced PLWH with plasma HIV RNA undetectable or detectable < 50 copies/ml switching to BIC/FTC/TAF. A previous 12-month monitoring was available, and the factors correlated with treatment efficacy. This retrospective multicenter study included PLWH who switched to BIC/FTC/TAF in the period of 2019-2022, and who were HBsAg and HCV RNA negative. The follow-up study times were 6 (T6), 12 (T12), 18 (T18), and 24 (T24) months after the switch (T0). Survival analysis with multiple-failure-per-subject design, Kaplan-Meier survival estimates, multivariate analysis of variance, multilevel linear regression, and a hierarchical ordered logistic model were applied. A total of 329 PLWH had plasma HIV RNA which was either undetectable or detectable at <50 copies/mL at T0, and 197 responded to all inclusion criteria: M/F 140/57; the median CD4+ cell count was 677 cells/mm3; and HIV RNA at T0 was undetectable in 108 patients. Most of the 197 patients (122, 61.9%) were on a previous INSTI-based regimen. HIV RNA undetectability was more frequent at each follow-up point in patients with HIV RNA that was undetectable at T0, and it showed a higher frequency throughout the follow-up period in patients with always-undetectable HIV RNA in the 12 months before the switch. A higher nadir CD4 cell count had a predictive role, and HBcAb positivity had no influence. In conclusion, the switch could be programmed and possibly delayed on a case-by-case basis in order to achieve persistent plasma HIV RNA undetectability. Undiagnosed loss of HBcAb has no detrimental consequences on the response to BIC/FTC/TAF.

Predictors of serious adverse events and non-response in cirrhotic patients with primary biliary cholangitis treated with obeticholic acid.

BACKGROUND & AIMS: Obeticholic acid (OCA) has recently been restricted in patients with primary biliary cholangitis (PBC) with "advanced cirrhosis" because of its narrow therapeutic index. We aimed to better define the predicting factors of hepatic serious adverse events (SAEs) and non-response in cirrhotic patients undergoing OCA therapy. METHODS: Safety and efficacy of treatment were evaluated in a cohort of consecutive PBC cirrhotic patients started with OCA. OCA response was evaluated according to the Poise criteria. Risk factors for hepatic SAEs and non-response were reported as risk ratios (RR) with 95% confidence intervals (CIs). RESULTS: One hundred PBC cirrhotics were included, 97 Child-Pugh class A and 3 class B. Thirty-one had oesophageal varices and 5 had a history of ascites. Thirty-three per cent and 32% of patients achieved a biochemical response at 6 and 12 months respectively. Male sex (adjusted-RR 1.75, 95%CI 1.42-2.12), INR (1.37, 1.00-1.87), Child-Pugh score (1.79, 1.28-2.50), MELD (1.17, 1.04-1.30) and bilirubin (1.83, 1.11-3.01) were independently associated with non-response to OCA. Twenty-two patients discontinued OCA within 12 months: 10 for pruritus, 9 for hepatic SAEs (5 for jaundice and/or ascitic decompensation; 4 for upper digestive bleeding). INR (adjusted-RR 1.91, 95%CI 1.10-3.36), lower albumin levels (0.18, 0.06-0.51), Child-Pugh score (2.43, 1.50-4.04), history of ascites (3.5, 1.85-6.5) and bilirubin (1.30, 1.05-1.56), were associated with hepatic SAEs. A total bilirubin≥1.4 mg/dl at baseline was the most accurate biochemical predictor of hepatic SAEs under OCA. CONCLUSIONS: An accurate baseline assessment is crucial to select cirrhotic patients who can benefit from OCA. Although OCA is effective in one third of cirrhotics, bilirubin level ≥1.4 mg/dl should discourage from its use.

Isolation and Sequencing of the First Case of Symptomatic MDR Salmonella enterica Subsp. Enterica ST40 in Human in Italy, July 2020.

Strains of drug-resistant nontyphoidal Salmonella spp. are emerging in livestock worldwide. We describe the first case of symptomatic multidrug-resistant (MDR) Salmonella enterica subsp. enterica in human and the genetic mechanisms at the basis of its antibiotic resistance. To control outbreaks, rapid identification and sequencing are necessary. Proactive research and notification are needed to evaluate the routes of transmission from livestock to humans and risk-management strategies of MDR Salmonella strains.

Epstein-Barr Virus (EBV) acute acalculous cholecystitis in an immunocompromised adult patient: a case report and a literature review of a neglected clinical presentation.

Primary Epstein-Barr virus (EBV) infection may present with self-limiting abdominal involvement, characterized by hepatitis with mild elevation of aminotransferases, splenomegaly, and rarely with acute acalculous cholecystitis (AAC). Usually, treatment of EBV related AAC is symptomatic, without the need for surgery. Here, we describe a severe case of AAC occurring as the first manifestation of infectious mononucleosis in a young adult woman, receiving treatment with interleukin 6 receptor (IL-6r) inhibitor for rheumatoid arthritis (RA); moreover, we have performed a review of the literature on EBV-related AAC.

Real-world experience with obeticholic acid in patients with primary biliary cholangitis.

BACKGROUND & AIMS: Obeticholic acid (OCA) is the second-line treatment approved for patients with primary biliary cholangitis (PBC) and an inadequate response or intolerance to ursodeoxycholic acid. We aimed to evaluate the effectiveness and safety of OCA under real-world conditions. METHODS: Patients were recruited into the Italian PBC Registry, a multicentre, observational cohort study that monitors patients with PBC at national level. The primary endpoint was the biochemical response according to Poise criteria; the secondary endpoint was the biochemical response according to normal range criteria, defined as normal levels of bilirubin, alkaline phosphatase (ALP), and alanine aminotransferase (ALT) at 12 months. Safety and tolerability were also assessed. RESULTS: We analysed 191 patients until at least 12 months of follow-up. Median age was 57 years, 94% female, 61 (32%) had cirrhosis, 28 (15%) had histologically proven overlap with autoimmune hepatitis (PBC-AIH). At 12 months, significant median reductions of ALP (-32.3%), ALT (-31.4%), and bilirubin (-11.2%) were observed. Response rates were 42.9% according to Poise criteria, and 11% by normal range criteria. Patients with cirrhosis had lower response than patients without cirrhosis (29.5% vs. 49.2%, p = 0.01), owing to a higher rate of OCA discontinuation (30% vs. 12%, p = 0.004), although with similar ALP reduction (29.4% vs. 34%, p = 0.53). Overlap PBC-AIH had a similar response to pure PBC (46.4% vs. 42.3%, p = 0.68), with higher ALT reduction at 6 months (-38% vs. -29%, p = 0.04). Thirty-three patients (17%) prematurely discontinued OCA because of adverse events, of whom 11 experienced serious adverse events. Treatment-induced pruritus was the leading cause of OCA discontinuation (67%). CONCLUSIONS: Effectiveness and safety of OCA under real-world conditions mirror those in the Poise trial. Patients with cirrhosis had lower tolerability. Overlap PBC-AIH showed higher ALT reduction at 6 months compared with patients with pure PBC. LAY SUMMARY: Obeticholic acid (OCA) was shown to be effective in more than one-third of patients not responding to ursodeoxycholic acid in a real-world context in Italy. Patients with cirrhosis had more side effects with OCA, and this led to suspension of the drug in one-third of patients. OCA was also effective in patients who had overlap between autoimmune hepatitis and primary biliary cholangitis.

Symptomatic congenital Cytomegalovirus deafness: the impact of a six-week course of antiviral treatment on hearing improvement.

Congenital Cytomegalovirus infection is the leading non-genetic cause of neurosensory deafness. We compared the outcomes of a treated group of children to an untreated group. The effect of antiviral therapy on hearing improvement between baseline and 2-year follow-up was statistically significant. These results suggest that the benefit of 6-week therapy is not limited to preventing further hearing deterioration.

[Thalamo-mesencephalic aspergillus abscess in a heart transplant subject: a case report and literature review]. / Ascesso aspergillare talamo-mesencefalico in un soggetto sottoposto a trapianto cardiaco: caso clinico e revisione della letteratura.

Cerebral aspergillosis is a rare and highly fatal infection that mainly affects immunocompromised patients. We report on a case of a heart transplanted Caucasian man, who arrived at our hospital because of the onset of diplopy. We performed a broad diagnostic work-up: the brain MRI showed a single ring-enhancing thalamo-mesencephalic area suggestive of abscess lesion; cerebrospinal fluid (CSF) analysis disclosed galactomannan and beta-D-glucan antigens. Thus the antifungal therapy was immediately started. We decided to discontinue the therapy 16 months later because of severe hepatic toxicity, given that the patient was persistently asymptomatic, brain imaging showed a progressive resolution of the abscess area and CSF antigen analysis was persistently negative. The follow-up at three months was unchanged.

Optimal fosamprenavir regimen to prevent lipid abnormalities.

We report our experience on the impact of different fosamprenavir boosted regimens on plasma lipid levels in 48 naive monoinfectd- HIV-seropositive patients. Eighteen months after starting antiretroviral therapy (ART), all patients showed a good immuno-virological response, with no statistically significant differences among the three groups; no changes in ART regimens were necessary and no adverse events were reported. On the contrary, a statistically significant difference among the three groups of patients was observed in cholesterol and triglyceride levels, since higher levels of cholesterol (including LDLs) and triglycerides were observed in patients taking the higher dose of ritonavir. (www.actabiomedica.it)