Heavily Treatment-Experienced Persons Living with HIV Currently in Care in Italy: characteristics, Risk Factors, and Therapeutic Options - the ICONA Foundation Cohort study

OBJECTIVES: Heavily Treatment-Experienced (HTE) People Living with HIV (PLWH) pose unique challenges due to limited antiretroviral treatment (ART) options. Our study aimed to investigate the prevalence and features of HTE individuals followed up inthe ICONA cohort as of December 31, 2021. METHODS: HTE were defined based on meeting specific conditions concerning their current ART and their ART history up to December 31, 2021.Descriptive statistics were performed by HTE status. Regression analyses explored factors associated with becoming HTE based on pre-ART patients' characteristics. Cluster dendrogram analysis provided insights into subgroups with inadequate responses based on CD4 counts and viral load (VL) trajectories Results: Among the 8,758 PLWH actively followed in our cohort, 163 individuals(1.9%),mainly female, younger, Italian, and infected through heterosexual contact,met the HTE criteria. A lower CD4 count at ART initiation (OR 1.60 per 100 cells/mmc lower CD4, 95% CI 1.06-2.41, p=0.03) and HCV Ab positivity (OR 1.90, 95% CI 1.16-3.11, p=0.01) were associated with higher HTE risk. Thirty PLWH exhibited ongoing immune-virological failure (18% of the HTE subgroup and 0.003% of the total population). Thirty PLWH exhibited ongoing immune-virological failure (i.e. with a current CD4 count200 copies/mL). A cluster analysis identified 13 (43%) with a current CD4 count<200 cells/mmc. Also, notably, 19/30 (63%) had major acquired resistance-associated mutations to at least one ARV drug class. CONCLUSIONS: HTE is rare in our cohort and tends to co-exist with major resistance mutations. A focused investigation into treatment history and immuno-virological response is warranted, particularly given the availability of new ARV drugs

Neuropsychiatric Disorders in Pediatric Long COVID-19: A Case Series

Few data are available regarding the incidence and the evolution of neuropsychiatric manifestations in children with a history of COVID-19. We herein report five consequent cases of pediatric patients with psychiatric and neurological symptoms of long COVID-19. All patients, mainly males, reported asymptomatic-to-mild COVID-19 and underwent home self-isolation. Abnormal movements, anxiety, and emotional dysregulation were the most recurrent symptoms observed from a few weeks to months after the resolution of the acute infection. A later onset was observed in younger patients. Blood tests and brain imaging resulted in negative results in all subjects; pharmacological and cognitive behavioral therapy was set. A multifactorial etiology could be hypothesized in these cases, as a result of a complex interplay between systemic and brain inflammation and environmental stress in vulnerable individuals. Longer follow-up is required to observe the evolution of neuropsychiatric manifestation in the present cohort and other young patients with previous SARS-CoV-2 infection

A Step Closer to the "Fourth 90": A Practical Narrative Review of Diagnosis and Management of Nutritional Issues of People Living with HIV

The quality of life of people living with HIV (PLWH) has remarkably increased thanks to the introduction of combined antiretroviral therapy. Still, PLWH are exposed to an increased risk of cardiovascular diseases, diabetes, chronic kidney disease, and liver disease. Hence, the purpose of this review is to summarize the current knowledge about diagnosis and nutritional management with specific indication of macro and micronutrients intake for the main comorbidities of PLWH. In fact, a prompt diagnosis and management of lifestyle behaviors are fundamental steps to reach the "fourth 90 ". To achieve an early diagnosis of these comorbidities, clinicians have at their disposal algorithms such as the Framingham Score to assess cardiovascular risk; transient elastography and liver biopsy to detect NAFLD and NASH; and markers such as the oral glucose tolerance test and GFR to identify glucose impairment and renal failure, respectively. Furthermore, maintenance of ideal body weight is the goal for reducing cardiovascular risk and to improve diabetes, steatosis and fibrosis; while Mediterranean and low-carbohydrate diets are the dietetic approaches proposed for cardioprotective effects and for glycemic control, respectively. Conversely, diet management of chronic kidney disease requires different nutritional assessment, especially regarding protein intake, according to disease stage and eventually concomitant diabetes

Risk of hepatocellular carcinoma development in long-term nucles(t)ide analog suppressed patients with chronic hepatitis B

Aim: In long-term nucleos(t)ide analog (NA) suppressed patients with chronic hepatitis B (CHB), hepatocellular carcinoma (HCC) can still develop. Few data exist on the incidence and the predictors of HCC development beyond the first five years in long-term treated patients. To assess the prevalence, incidence, and risk factors for HCC development in a real-life cohort of successfully NA-treated CHB patients for more than five years.Methods: All CHB patients under NAs for ≥ 60 months with stable virologic response were enrolled. HCC surveillance was carried out using liver ultrasound and dosing of serum alpha-fetoprotein every year in patients with CHB and every six months in cirrhotic patients. The baseline PAGE-B score was calculated for each patient.Results: 343 patients (76% male, 86% HBeAg-negative, 30% cirrhotic) were enrolled. During a median (IQR) follow-up of 144 (105-182) months, 21 patients (6%) developed HCC despite virologic suppression (incidence rate 40 cases/1000 person-years follow-up). In multivariate analysis, higher PAGE B score [adjusted Hazard Ratio, aHR 1.26 (95%CI: 1.13-1.54), P = .022] and cirrhosis [aHR 9.71 (95%CI: 2.02-46.48), P = .005] were predictors of HCC development. PAGE B score showed a significant association with HCC (R2 0.225, P &lt; .001) and good prognostic capacity (AUC 0.863) of HCC.Conclusions: Our results confirm that in successfully NA-treated CHB patients, sustained viral replication suppression does not abolish the risk of HCC. The PAGE-B score could be a useful tool for identifying high-risk subjects

Doravirine Plus Integrase Strand Transfer Inhibitors as a 2-Drug Treatment–Switch Strategy in People Living with HIV: The Real-Life DORINI Multicentric Cohort Study

Background: Few data are available about the efficacy, durability, and tolerability of doravirine (DOR) + integrase strand inhibitors (INI) as a switching strategy among antiretroviral therapy (ART)-experienced people living with HIV (PLWH).Setting: Retrospective, multicenter cohort study investigating the durability, efficacy, and tolerability of 2 off-label drug associations of DOR + INI among ART-experienced PLWH.Methods: The study included PLWH who switched to DOR combined with either raltegravir (RAL) or dolutegravir (DTG) between June 1, 2020, and December 31, 2021, with at least 1 follow-up (FU) visit. Virologic, biometric, and metabolic parameters were evaluated at baseline (T0) and at 1-3 (T1), 6 (T2), and 12 (T3) months. Univariate and multivariate survival analyses assessed the 28-week probability of persistence on the regimens. Patient satisfaction was measured using the HIV Treatment Satisfaction Questionnaire.Results: Ninety-five PLWH were included, 52 in DOR + RAL and 43 in DOR + DTG. Six treatment discontinuations were reported during a mean of 37 (+/- 17) weeks of FU (incidence of 2.7 x 1000 person-weeks FU). Only 2 were the result of virological failure without resistance mutations. DOR + DTG demonstrated significantly higher 28-week persistence than DOR + RAL (HR 1.90, 95% CI: 1.24-2.90, log-rank: P = 0.003). Weight, waist circumference, and fasting lipids reduced considerably at T3 vs T0. Overall, high satisfaction with the new treatment was reported, particularly in the DOR + RAL (68 (64-72)/72), compared with the DOR + DTG group (58 (50-65)/72, P&lt; 0.001).Conclusions: Our experience revealed few treatment discontinuations, improved metabolic parameters, and high patient satisfaction among ART-experienced PLWH switching to DOR combined with INI, irrespective of the specific INI used

Lost to follow-up: a challenge over 10 years

The loss of patients to follow up is a major issue related to HIV management. Our research was aimed to evaluate, in a single Italian centre, the rate of patients lost to follow-up (LFU) over 10 years, to describe their socio-demographic and clinical features, and to identify predictors of disengagement from care. Between 2008 and 2017, 563 subjects were LFU. Over the years, the proportion of LFU on the number of patients followed per year, decreased from 6.5% in 2008 to 4.8% in 2017 (p for trend = 0.255). Four different subgroups were identified among LFU:116 patients resulted untraceable; 192 had died; 144 were re-engaged elsewhere; 111 were subsequently re-engaged in our centre. Old age (OR 1.08, 95%, CI = 1.06-1.11; p &lt; 0.001), AIDS (OR = 1.66, 95% CI = 1.04-2.64; p = 0.031), drug addiction (OR = 1.91, 95% CI = 1.07-3.41; p = 0.027) were predictors of death at multivariable analysis. Main predictors of being untraceable were non-Italian nationality (OR = 4.23, 95% CI = 2.19-8.16; p &lt; 0.001) and a short history of cART (OR = 0.93, 95% CI = 0.88-0.99; p = 0.026). Subjects living far from our Centre were often re-engaged elsewhere (OR = 2.36, 95% CI = 1.34-4.15; p = 0.002). According to our analysis, the problem LFU is still relevant: strategies to empower retention in care are thus necessary

Natural SARS-CoV-2 Infection Affects Neutralizing Activity in Saliva of Vaccinees

BACKGROUND: SARS-CoV-2 transmission mainly occurs through exposure of the upper airway mucosa to infected secretions such as saliva, which are excreted by an infected person. Thus, oral mucosal immunity plays a central role in the prevention of and early defense against SARS-CoV-2 infection. Although virus-specific antibody response has been extensively investigated in blood samples of SARS-CoV-2-infected patients and vaccinees, local humoral immunity in the oral cavity and its relationship to systemic antibody levels needs to be further addressed. MATERIAL AND METHODS: We fine-tuned a virus neutralization assay (vNTA) to measure the neutralizing activity (NA) of plasma and saliva samples from 20 SARS-CoV-2-infected (SI), 40 SARS-CoV-2-vaccinated (SV), and 28 SARS-CoV-2-vaccinated subjects with a history of infection (SIV) using the “wild type” SARS-CoV-2 lineage B.1 (EU) and the Delta (B.1.617.2) strains. To validate the vNTA results, the presence of neutralizing antibodies (NAbs) to the spike receptor binding domain (RBD) was evaluated with an ELISA assay. RESULTS: NA to SARS-CoV-2 lineage B.1 (EU) was present in plasma samples from all the tested subjects, with higher titers in SIV compared to both SI and SV. Conversely, NA was detected in saliva samples from 10.3% SV, 45% SI, and 92.6% SIV, with significantly lower titers in SV compared to both SI and SIV. The detection of NAbs in saliva reflected its reduced NA in SV. DISCUSSION: The difference in NA of plasma vs. saliva was confirmed in a vNTA where the SARS-CoV-2 B.1 and Delta strains were tested head-to-head, which also revealed a reduced NA of both specimens compared to the B.1 variant. CONCLUSIONS: The administration of SARS-CoV-2 vaccines was associated with limited virus NA in the oral cavity, as measured in saliva and in comparison to plasma. This difference was more evident in vaccinees without a history of SARS-CoV-2 infection, possibly highlighting the importance of local exposure at the site of virus acquisition to effectively prevent the infection and block its spread. Nevertheless, the presence of immune escape mutations as possibly represented by the SARS-CoV-2 Delta variant negatively affects both local and systemic efficacy of NA associated with vaccination

HIV rapid test in a community setting as a strategy to improve access to HIV testing: data from a multicentre experience in Italy

4,000 new HIV diagnoses and approximately 800 AIDS cases are still reported annually in Italy. Improving public awareness and bringing out HIV-undiagnosed individuals are keystones to progress towards the control of the HIV epidemic. For this purpose, the Open HIV TEST project was organized and delivered by the Italian NGO Anlaids, together with local infectious diseases specialists, in order to provide free access to HIV testing outside the healthcare setting. Between October 2017 and February 2019 six Open HIV TEST initiatives were delivered in six Italian cities (3 northern cities, 1 central and 2 southern cities). In all, 581 people were tested: the overall prevalence of HIV test reactivity was 0.7%. Participants were also asked about previous screenings and about their satisfaction with the initiative: previous HIV screening due to pregnancy or surgical procedures was reported mainly by participants in northern centres (p&lt;0.001); finally, the initiative was considered useful and noteworthy by 99% of participants. Prevalence of HIV test reactivity in our experience was in line with national data. Our experience suggests that active testing and counselling strategies in community settings should be recommended and institutionalized by local health authorities in line with the 90-90-90 global strategy

Salivary miRNA Profiles in COVID-19 Patients with Different Disease Severities

: The oral mucosa is the first site of SARS-CoV-2 entry and replication, and it plays a central role in the early defense against infection. Thus, the SARS-CoV-2 viral load, miRNAs, cytokines, and neutralizing activity (NA) were assessed in saliva and plasma from mild (MD) and severe (SD) COVID-19 patients. Here we showed that of the 84 miRNAs analyzed, 8 were differently expressed in the plasma and saliva of SD patients. In particular: (1) miRNAs let-7a-5p, let-7b-5p, and let-7c-5p were significantly downregulated; and (2) miR-23a and b and miR-29c, as well as three immunomodulatory miRNAs (miR-34a-5p, miR-181d-5p, and miR-146) were significantly upregulated. The production of pro-inflammatory cytokines (IL-1β, IL-2, IL-6, IL-8, IL-9, and TNFα) and chemokines (CCL2 and RANTES) increased in both the saliva and plasma of SD and MD patients. Notably, disease severity correlated with NA and immune activation. Monitoring these parameters could help predict disease outcomes and identify new markers of disease progression

General Practitioners as partners for a shared management of chronic HIV infection: An insight into the perspectives of Italian People Living with HIV

Is it possible to achieve a collaboration between Infectious Diseases (ID) Specialists and General Practitioners (GPs) in the management of chronic HIV infection? A cross sectional survey was conducted among People Living with HIV (PLWHIV) attending the outpatient services of four Italian Infectious Diseases Centers to understand to which extent patients trust their GPs and involve them in the management of their chronic condition. Information about level of communication with GPs, subjective perception of the disease, and presence of co-medications were collected and matched with socio-demographic data using \u3c72statistics. A p&lt;0.05 was considered statistically significant. From December 2019 to February 2020, 672 patients completed the survey, 59% males and 56% &gt;50 years. Overall, 508 patients (76%) had informed GPs about HIV-positivity. Communication of diagnosis was significantly associated with age &gt;50years, lower education level, history of disease &gt;10 years and residency in Northern Italy. The "Undetectable = Untrasmittable" (U = U) concept was investigated as an indirect measure of perceived stigma. 23% of subjects was unaware of its meaning. Despite undetectable status, 50% of PLWHIV found difficult to communicate their condition to GPs, especially married (52% vs 48% of unmarried, p = 0.003), well-educated patients (51% vs 48, p = 0.007), living in Southern vs Northern Italy (52% vs 46%, p&lt; 0.001). More than 75% of the participants consulted the ID specialist for co-medications and DDIs management, often complaining a lack of communication of the former with GPs. Overall, a good level of communication between PLWHIV and GPs was outlined, even if a wider involvement of the latter in HIV care is desirable