Unexpected CD4 decay, hidden adherence gaps, resilience, and the need for long-acting therapy in a single HIV outpatients' cohort.

This single-centre, single-cohort study examines hidden non-adherence to antiretroviral therapy in a setting of persistent optimal viral suppression but concordant absolute and percent CD4 decay by >10% from the previous test. After the finding of important drug holidays in two virologically suppressed patients, between January 2021 and January 2022 all PLWH who fulfilled CD4 decay criteria were asked for how long therapy was interrupted, how many days before re-testing CD4 and HIV RNA was it resumed and the reason for interruption. Of 668 HIV-infected subjects, 61 fulfilled the pre-specified criteria for significant CD4 decay and 15 (2.25% of the total, 25% of the CD4 decay group) admitted long-lasting treatment interruptions, compensated by treatment resumption before the subsequent testing. Eleven treatment interruptions exceeded 28 days, and none was shorter than 15 days. CD4 recovery was worse at 6 months in non-adherent subjects (-0.5 vs + 16/mmc, p < 0.0001) and in non adherence vs immune decay time-related with COVID-19 (0 vs + 22/mmc, p < 0.0001). Reasons for interrupting treatment were travel, psychological, poverty-related, addiction and sentimental sphere problems. Long-acting regimens, with stringent control of precision in timely administration, may protect PLWH from damaging their health status and possibly transmit HIV.

Concomitant diagnosis of sexually transmitted infections and human monkeypox in patients attending a sexual health clinic in Milan, Italy.

In 2022, many monkeypox (MPX) outbreaks have been documented in countries where MPX was not endemic. It spread all around the world, especially in European Union and United States. While MPX is classically considered to be transmitted through close contact with lesions, the hypothesis of sexual transmission has been proposed. This study considered a total of 49 patients suspected for MPX that were also tested for other sexually transmitted infections (STIs), including Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, and Trichomonas vaginalis. The data from coinfected patients suggested that MPXV and STIs might share the same route of inoculum, corroborating the hypothesis of possible sexual transmission for the emerging poxvirus. And like any other STI, MPX should be considered without stigmatization.

Efficacy and durability of two- vs. three-drug integrase inhibitor-based regimens in virologically suppressed HIV-infected patients: Data from real-life ODOACRE cohort.

OBJECTIVES: The aim of the present study was to compare the efficacy and durability of treatment switch to two-drug (2DR) vs. three-drug (3DR) integrase inhibitor (InSTI)-based regimens in a real-life setting. METHODS: Within the ODOACRE cohort, we selected adult patients with HIV RNA < 50 copies/mL switching to an InSTI-based 2DR or 3DR. Survival analyses were performed to estimate the probability of virological failure (VF, defined as one HIV RNA > 1000 copies/mL or two consecutive HIV RNA > 50 copies/mL) and treatment discontinuation (TD, defined as any modification, intensification or interruption of the regimen), and to evaluate their predictors. RESULTS: Overall, 1666 patients were included, of whom 1334 (80%) were treated with a 3DR (19.9%, 25.0% and 55.1% elvitegravir-, raltegravir- and dolutegravir-based, respectively) and 332 (20%) with a 2DR (79.2% dolutegravir + lamivudine and 20.8% dolutegravir + rilpivirine). Over a median (interquartile range) follow-up of 100 (52-150) weeks, 52 (3.1%) patients experienced VF with an incidence of 1.5/100 person-year of follow-up (PYFU). The estimated 96-week probability of VF was similar for the 2DR and 3DR groups (2.3% vs. 2.8%, P = 0.53), but it was higher for elvitegravir (4.9%) and raltegravir (5.0%) than for dolutegravir (1.5%) (P = 0.04). Four hundred (24%) patients discontinued their InSTI-based regimen, with an incidence of 11.3/100 PYFU. At 96 weeks, 3DRs showed a higher probability of TD for any reason (20.6% vs. 11.2%, P < 0.001) and TD for toxicity (9.0% vs. 6.6%, P = 0.02) when compared with 2DRs. A higher risk of TD for central nervous system toxicity was observed for dolutegravir than for elvitegravir and raltegravir (4.0% vs. 2.5% vs. 0.6%, P = 0.005). CONCLUSIONS: In virologically suppressed HIV-infected patients, 2DRs showed an efficacy similar to 3DRs but with better tolerability.

Short-term inhibition of SARS-CoV-2 by hydrogen peroxide in persistent nasopharyngeal carriers.

Asymptomatic and convalescent coronavirus disease 2019 (COVID-19) subjects may carry severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for months in their upper respiratory ways. Desiring to permanently clean the mucosal surfaces, we investigated the chemical agents that fit to rapidly degrade the virus. Among these, hydrogen peroxide, initially tested by two of us for tolerability, showed both good performance and acceptable side effects (burning sensation for 15-20 s). We contacted circles of family physicians and the ATS Milano (Territorial Assistance and Prevention Service), and we tested this procedure on eight persistent carriers of SARS-CoV-2, performing swabs before the procedure and after it until the reappearance of the virus or until 14 days (the incubation period), keeping the surfaces clean with a hypertonic solution. Our patients had a median time from exposure or symptom onset of 111 days, and three had relapsed after being declared "cured" (two consecutive negative swabs after quarantine). One patient had a baseline negative swab and was excluded, and two successfully ended the 14 days' course, four suppressed viral elimination for 72 h, and one for 48 h, all rebounding to weak positive (cycle thresholds above 24). Although temporarily effective, such measures may have some place in the control of viral shedding to protect the most fragile subjects.

Emerging drugs for the treatment of HIV/AIDS: a review of 2019/2020 phase II and III trials.

Introduction: The study of emerging drug trials to treat people living with HIV (PLWH) helps to understand any advantages and disadvantages of therapies that will be available on the market in the short-term future as well as the mechanisms underlying a better cure.Areas covered: This review analyzes phase 2 and 3 clinical trials published between 2019 and 2020 concerning six different emerging drugs. The majority of the trials focus on long acting drugs, but also on new orally administered compounds.Expert opinion: The biggest news in antiretroviral therapy (ART) is the approval of cabotegravir/rilpivirine as a complete long-acting (LA) therapeutic regimen. It paves the way for an innovation that may change the paradigms of HIV treatment in the long term, albeit it will not be obvious to implement and treatment adherence still needs to be fully evaluated. Results of phase 3 Islatravir trials are awaited. Lenacapavir may soon reach phase 3. These drugs may pave the way for 6-month ART in the next future. Fostemsavir has been recently approved. Albuvirtide, a fusion inhibitor approved in China, presents several limitations for its intravenous use only. UB-421 and VRC01 are monoclonal antibodies against HIV. This emerging technology has shown interesting results but needs further studies.

Dolutegravir Plus Rilpivirine as a Switch Option in cART-Experienced Patients: 96-Week Data.

BACKGROUND: Data from clinical studies confirm the efficacy of switching to dolutegravir (DTG) plus rilpivirine (RPV) in selected patients. OBJECTIVE: The primary objective is to report the 96-week virological suppression in our cohort, assessing the durability of this strategy in complicated situations. The secondary objective is to describe the safety and metabolic profile. METHODS: All patients who had switched to DTG plus RPV between October 1, 2014, and September 30, 2015, were analyzed using a retrospective-prospective design, approved by ethics committees. Routine metabolic, immunological, and virological data were regularly sent to the coordinating center. Viral control was classified as HIV-1 RNA ≥50 copies/mL, 1 to 49 copies/mL, or undetectable (no virus detected [NVD]). RESULTS: We followed 145 patients for a median of 101 weeks. The median age was 52 years; 31.7% were women, and 9.6% non-Caucasian; 50.3% had failed at least 1 antiretroviral regimen; and 15% had ≥50 copies/mL at baseline. The reasons for switching were as follows: simplification (51.7%), toxicity (36.5%), drug-drug interactions (6.9%), persistent low-level viremia (3.0%), nonadherence (2.1%), and viral failure (1.4%). By week 96, seven patients dropped out. At week 96, none had ≥50 HIV-1 RNA copies/mL, 138 (95.2%) had <50 copies/mL, and 123 (84.8%) had NVD. The low- to high-density lipoprotein cholesterol (LDL-C/HDL-C) ratio decreased significantly ( P = 0.04). Of the 287 baseline altered laboratory parameters, 32.7% normalized by week 96. Serum glucose and total- and LDL-cholesterol normalization were statistically significant. CONCLUSIONS: Switching to DTG plus RPV improved viral suppression and LDL-C/HDL-C ratio.

A dual regimen of ritonavir/darunavir plus dolutegravir for rescue or simplification of rescue therapy: 48 weeks' observational data.

BACKGROUND: Dolutegravir (DTG) plus darunavir/ritonavir (DRV/r) is a simple combination of drugs that has the best genetic barrier to HIV-1 resistance and may be fit for salvage therapy. METHODS: All HIV-1-infected subjects treated with DTG plus DRV/r between March 2014 and September 2015 in eight Italian centres were included in the analysis. The main metabolic data, efficacy parameters and safety data routinely collected were provided. This observational study is aimed to assess the efficacy of such approach. The primary end-point was the proportion of subjects achieving or maintaining virologic suppression <50 copies/mL at week 24. Secondary end points were maintaining virologic suppression in the follow-up (weeks 48 and 96) and safety. RESULTS: One hundred and thirty subjects were followed for a median of 56 months. Reasons for switching were simplification (44.6%), viral failure (30%), toxicity (16.9%), non-adherence (4.6%), persistent low-level viremia (3.1%), and drug-drug interaction (0.8%). At baseline, 118 subjects had documented resistance to 1 to 5 antiretroviral classes while 12 had viral rebound at a time when genotypic tests were not yet available. Seventeen and 14 subjects took DRV/r and DTG twice daily, respectively. One subject was lost to follow-up, one discontinued for liver enzymes' elevation, one died of illicit drug abuse and one of cancer-related complications. The proportion of subjects with ongoing HIV replication dropped from 40% to 6.1%. Those with undetectable viral load increased from 38.5% to 76.2%. At week 48, 17.7% had HIV RNA between 1 and 49 copies/mL. The number of subjects with altered serum glucose, creatinine, ALT, AST, total-, HDL- and LDL-cholesterol, triglycerides and MDRD <90 mL/min decreased by week 48, while those having MDRD <60 mL/min remained 4.6%. Overall 90/283 baseline laboratory alterations returned to normality. CONCLUSIONS: Switching to DTG plus DRV/r proved to be safe, suppressing viral replication without metabolic impact.

OPERA: responses to peginterferon and ribavirin therapy in a subgroup of interferon-naïve patients with HIV/HCV genotype 2/3 co-infection in Italy.

BACKGROUND & AIMS: Hepatitis C virus (HCV) genotype 3 (G3) is common among HIV/HCV co-infected individuals and associated with moderate sustained virological response (SVR) rates with pegylated interferon (PEG-IFN) plus ribavirin (RBV) therapy, while G2 is less frequent and associated with higher SVR. To determine SVR and other response rates, identify SVR predictors and analyse differences between G2 and G3 with PEG-IFN/RBV in a large HIV/HCV G2/3 patient population. METHODS: This subgroup analysis of the prospective, observational OPERA (Optimized Pegylated interferon Efficacy and anti-Retroviral Approach) study was conducted between 2005 and 2011 in Italy in PEG-IFN/RBV-naïve HIV/HCV patients. The primary efficacy endpoint was SVR rate (HCV RNA <50 IU/ml or undetectable 24 weeks after end-of-treatment). RESULTS: Five hundred and fifty-six HCV G2/3 patients (G2 n = 60; G3 n = 496) were treated with PEG-IFN alfa-2a 180 µg/week or PEG-IFN alfa-2b 1.5 µg/kg, + RBV 13.6 ± 2.3 (mean ± SD) mg/kg/day for median 47 (26-54) weeks. SVR rates were 57.7%, 68.3% and 56.5% for G2/3, G2 and G3 respectively) and RVR rates were 53.2%, 57.1% and 45.8% respectively. Independent SVR predictors were undetectable baseline HIV RNA [adjusted odds ratio (AOR), 2.64; 95% CI: 1.523-4.565, P = 0.0005], age (AOR 0.95 per year; 95% CI: 0.908-0.994, P = 0.0258) and anti-HCV treatment duration (AOR 1.034 per week; 95% CI: 1.013-1.057, P = 0.0019). CONCLUSIONS: Undetectable HIV RNA, longer anti-HCV treatment adherence and younger age were independent SVR predictors in treatment-naïve HIV/HCV G2/3 patients receiving PEG-IFN/RBV. Suppressing HIV RNA replication before anti-HCV therapy and increasing adherence to PEG-IFN/RBV treatment SVR rates may improve SVR.

Comparison of the pharmacokinetics of raltegravir given at 2 doses of 400 mg by swallowing versus one dose of 800 mg by chewing in healthy volunteers: a randomized, open-label, 2-period, single-dose, crossover phase 1 study.

BACKGROUND: The pharmacokinetics of raltegravir (RAL) in HIV patients is characterized by high interindividual and intraindividual variability. We documented previously that HIV patients taking RAL at 400 mg bid by chewing the tablets had significantly higher drug absorption and reduced pharmacokinetic variability than patients taking the drug by swallowing the tablets. This study extends our previous findings. METHODS: An open-label, 2-period crossover study compared the pharmacokinetics of 2 doses of RAL given at 400 mg every 12 hours (that mimics a bid administration) by swallowing with 1 dose of 800 mg (that mimics a qd administration) by chewing the tablets in 12 healthy volunteers. RAL plasma concentrations were measured by a chromatographic method coupled with mass spectrometry. RESULTS: Subjects taking RAL by chewing had significantly higher drug exposure (RAL area under the curve[AUC](0-24): 40722 ± 14843 versus 21753 ± 12229 ng · h/mL, P < 0.0001) and reduced pharmacokinetic variability compared with those taking the drug by swallowing the whole tablet, with no difference in the minimum RAL concentrations (RAL C(min): 36 ± 23 versus 43 ± 23 ng/mL, P = 0.298). Subjects taking RAL by chewing the tablets had significantly higher drug absorption and reduced pharmacokinetic variability compared with those taking the drug by swallowing. No differences were observed in the minimum RAL concentrations. CONCLUSIONS: RAL at 800 mg once daily by chewing the tablets may represent a novel therapeutic option for the treatment of HIV being associated with higher drug absorption, reduced pharmacokinetic variability, and potentially better compliance compared with patients swallowing the 400-mg bid intact tablets.

Nanoformulation of antiretroviral drugs enhances their penetration across the blood brain barrier in mice.

Eradication of virus by sanctuary sites is a main goal in HIV management. The central nervous system (CNS) is a classic model of sanctuary where viral replication occurs despite a complete viral suppression in peripheral blood. In recent years, nanotechnologies have provided a great promise in the eradication of HIV from the CNS. We hereby demonstrate for the first time that the structurally complex antiretroviral drug enfuvirtide (Enf), which normally is unable to penetrate the cerebrospinal fluid, is allowed to cross the blood brain barrier (BBB) in mice by conjugation with a nanoconstruct. Iron oxide nanoparticles coated with an amphiphilic polymer increase Enf translocation across the BBB in both in vitro and in vivo models. The mechanism involves the uptake of nanoconjugated-Enf in the endothelial cells, the nanocomplex dissociation and the release of the peptide, which is eventually excreted by the cells in the brain parenchyma. FROM THE CLINICAL EDITOR: Despite the success of cocktail therapy of antiretroviral drugs, the complete eradication of HIV remains elusive, due to existence of viral sanctuary sites. The authors showed in this study that an antiretroviral drug complexed with iron oxide nanoparticles and coated with PMA amphiphilic polymer crosses the blood brain barrier. Furthermore, there was significant anti-viral activity. The results would aid further drug designs to eradicate HIV.

Analysis and clinical determinants of post-COVID-19 syndrome in the Lombardy region: evidence from a longitudinal cohort study.

OBJECTIVE: To define macro symptoms of long COVID and to identify predictive factors, with the aim of preventing the development of the long COVID syndrome. DESIGN: A single-centre longitudinal prospective cohort study conducted from May 2020 to October 2022. SETTING: The study was conducted at Luigi Sacco University Hospital in Milan (Italy). In May 2020, we activated the ARCOVID (Ambulatorio Rivalutazione COVID) outpatient service for the follow-up of long COVID. PARTICIPANTS: Hospitalised and non-hospitalised patients previously affected by COVID-19 were either referred by specialists or general practitioners or self-referred. INTERVENTION: During the first visit, a set of questions investigated the presence and the duration of 11 symptoms (palpitations, amnesia, headache, anxiety/panic, insomnia, loss of smell, loss of taste, dyspnoea, asthenia, myalgia and telogen effluvium). The follow-up has continued until the present time, by sending email questionnaires every 3 months to monitor symptoms and health-related quality of life. PRIMARY AND SECONDARY OUTCOME MEASURES: Measurement of synthetic scores (aggregation of symptoms based on occurrence and duration) that may reveal the presence of long COVID in different clinical macro symptoms. To this end, a mixed supervised and empirical strategy was adopted. Moreover, we aimed to identify predictive factors for post-COVID-19 macro symptoms. RESULTS: In the first and second waves of COVID-19, 575 and 793 patients (respectively) were enrolled. Three different post-COVID-19 macro symptoms (neurological, sensorial and physical) were identified. We found significant associations between post-COVID-19 symptoms and (1) the patients' comorbidities, and (2) the medications used during the COVID-19 acute phase. ACE inhibitors (OR=2.039, 95% CI: 1.095 to 3.892), inhaled steroids (OR=4.08, 95% CI: 1.17 to 19.19) and COVID therapies were associated with increased incidence of the neurological macro symptoms. Age (OR=1.02, 95% CI: 1.01 to 1.04), COVID-19 severity (OR=0.42, 95% CI: 0.21 to 0.82), number of comorbidities (OR=1.22, 95% CI: 1.01 to 1.5), metabolic (OR=2.52, 95% CI: 1.25 to 5.27), pulmonary (OR=1.87, 95% CI: 1.10 to 3.32) and autoimmune diseases (OR=4.57, 95% CI: 1.57 to 19.41) increased the risk of the physical macro symptoms. CONCLUSIONS: Being male was the unique protective factor in both waves. Other factors reflected different medical behaviours and the impact of comorbidities. Evidence of the effect of therapies adds valuable information that may drive future medical choices.

Duration of first-line antiretroviral therapy with tenofovir and emtricitabine combined with atazanavir/ritonavir, efavirenz or lopinavir/ritonavir in the Italian ARCA cohort.

OBJECTIVES: To explore the durability of three first-line tenofovir/emtricitabine-based regimens in combination with atazanavir/ritonavir, efavirenz or lopinavir/ritonavir in HIV-1-infected patients. PATIENTS AND METHODS: A retrospective, longitudinal, multicentre analysis of adult patients enrolled in the Antiretroviral Resistance Cohort Analysis (ARCA), a national prospective observational cohort of HIV-1-infected patients followed up at more than 100 clinical and laboratory units in Italy. Patients eligible were those starting first-line antiretroviral therapy between 1 June 2004 and 15 April 2011 and who were followed up for at least 6 months. The primary endpoint was durability, defined as the time from antiretroviral therapy initiation to first treatment modification. Time-dependent events were analysed by the Kaplan-Meier approach and the Cox proportional hazard model. RESULTS: There are 26,000 HIV-infected patients in the ARCA database, of whom 1654 met study inclusion criteria. Six hundred and thirty-nine (38.6%) received efavirenz, 321 (19.4%) received atazanavir/ritonavir and 694 (41.9%) received lopinavir/ritonavir as a first-line regimen. Over a total observation period of 88 months, equivalent to more than 2805 person-years of follow-up, 618 patients underwent treatment modification. Lopinavir/ritonavir, given twice daily, was associated with a higher discontinuation rate than efavirenz- and atazanavir-based regimens [hazard ratio (HR) 1.83, 95% confidence interval (CI) 1.56-2.15, P = 0.001]. Comparing the once-daily regimens, the rate of discontinuation of efavirenz was higher than that of atazanavir/ritonavir (HR 1.39, 95% CI 1.06-1.83, P = 0.016). CONCLUSIONS: Significant differences in treatment duration were observed among the three studied regimens. Once-daily regimens exhibited greater durability than the twice-daily regimen. Among the specific regimens examined, tenofovir/emtricitabine plus atazanavir/ritonavir showed the greatest durability.

Hydroxychloroquine drastically reduces immune activation in HIV-infected, antiretroviral therapy-treated immunologic nonresponders.

Despite optimal suppression of HIV replication, restoration of CD4(+) T cells is not always achieved in antiretroviral therapy-treated individuals. Defective CD4 recovery in immunologic nonresponders is possibly associated with TLR-mediated immune activation driven by alterations of gut permeability. Hydroxychloroquine (HCQ) reduces endosomal TLR signaling; thus, we verified whether HCQ could dampen immune activation and be associated with an increase in CD4(+) T cells. To this end, we enrolled in a prospective study 20 HIV-infected immunologic nonresponders (CD4 count < 200 cells/mL or CD4 increase < 5% in the last 12 months) who received 400 mg/day HCQ for 6 months. HCQ had a notable impact on immune activation as shown by significant modifications of the following parameters: (1) reduced plasma lipopolysaccharide; (2) decreased TLR4-expressing CD14(+) cells, TLR4-mediated signal transduction, and mRNA synthesis; (3) reduced percentages of activated CD4(+) (CD4(+)/Ki67(+)) and CD14(+) (CD14(+)/CD69(+)) cells; (4) increased T-regulatory cells (Tregs), naive Tregs, and TLR4-expressing Tregs; (5) augmented plasmacytoid dendritic cells and reduced IFNα-secreting plasmacytoid dendritic cells; and (6) reduced IL-6 and TNFα production. HCQ-induced immune modulation was associated with increased percentages of circulating CD4(+) T cells and was mostly retained 2 months after therapy interruption. HCQ reduces lipopolysaccharide/TLR-mediated immune activation; this compound could be a useful immunomodulant in HIV-infected patients. This study is registered at EutraCT as 2009-012499-28 with study number HLS01/2009-1-16-03-2009.

Efficacy and Durability of Dolutegravir- or Darunavir-Based Regimens in ART-Naïve AIDS- or Late-Presenting HIV-Infected Patients.

BACKGROUND: Since limited data are available, we aimed to compare the efficacy and durability of dolutegravir and darunavir in advanced naïve patients. METHODS: Retrospective multicenter study including AIDS- or late-presenting (def. CD4 ≤ 200/µL) HIV-infected patients starting dolutegravir or ritonavir/cobicistat-boosted darunavir+2NRTIs. Patients were followed from the date of first-line therapy initiation (baseline, BL) to the discontinuation of darunavir or dolutegravir, or for a maximum of 36 months of follow-up. RESULTS: Overall 308 patients (79.2% males, median age 43 years, 40.3% AIDS-presenters, median CD4 66 cells/µL) were enrolled; 181 (58.8%) and 127 (41.2%) were treated with dolutegravir and darunavir, respectively. Incidence of treatment discontinuation (TD), virological failure (VF, defined as a single HIV-RNA > 1000 cp/mL or two consecutive HIV-RNA > 50 cp/mL after 6 months of therapy or after virological suppression had been achieved), treatment failure (the first of TD or VF), and optimal immunological recovery (defined as CD4 ≥ 500/µL + CD4 ≥ 30% + CD4/CD8 ≥ 1) were 21.9, 5.2, 25.6 and 1.4 per 100 person-years of follow-up, respectively, without significant differences between dolutegravir and darunavir (p > 0.05 for all outcomes). However, a higher estimated probability of TD for central nervous system (CNS) toxicity (at 36 months: 11.7% vs. 0%, p = 0.002) was observed for dolutegravir, whereas darunavir showed a higher probability of TD for simplification (at 36 months: 21.3% vs. 5.7%, p = 0.046). CONCLUSIONS: Dolutegravir and darunavir showed similar efficacy in AIDS- and late-presenting patients. A higher risk of TD due to CNS toxicity was observed with dolutegravir, and a higher probability of treatment simplification with darunavir.

Evaluation of the immune benefits of two probiotic strains Bifidobacterium animalis ssp. lactis, BB-12® and Lactobacillus paracasei ssp. paracasei, L. casei 431® in an influenza vaccination model: a randomised, double-blind, placebo-controlled study.

The present study investigated the ability of Bifidobacterium animalis ssp. lactis (BB-12®) and Lactobacillus paracasei ssp. paracasei (L. casei 431®) to modulate the immune system using a vaccination model in healthy subjects. A randomised, double-blind, placebo-controlled, parallel-group study was conducted in 211 subjects (56 % females, mean age 33·2 (sd 13·1) years). Subjects consumed a minimum of 109 colony-forming units of BB-12® (capsule) or L. casei 431® (dairy drink) or a matching placebo once daily for 6 weeks. After 2 weeks, a seasonal influenza vaccination was given. Plasma and saliva samples were collected at baseline and after 6 weeks for the analysis of antibodies, cytokines and innate immune parameters. Changes from baseline in vaccine-specific plasma IgG, IgG1 and IgG3 were significantly greater in both probiotic groups v. the corresponding placebo group (L. casei 431®, P = 0·01 for IgG; P < 0·001 for remaining comparisons). The number of subjects obtaining a substantial increase in specific IgG (defined as ≥ 2-fold above baseline) was significantly greater in both probiotic groups v. placebo (BB-12®, P < 0·001 for IgG, IgG1 and IgG3; L. casei 431®, P < 0·001 for IgG1 and IgG3). Significantly greater mean fold increases for vaccine-specific secretory IgA in saliva were observed in both probiotic groups v. placebo (BB-12®, P = 0·017; L. casei 431®, P = 0·035). Similar results were observed for total antibody concentrations. No differences were found for plasma cytokines or innate immune parameters. Data herein show that supplementation with BB-12® or L. casei 431® may be an effective means to improve immune function by augmenting systemic and mucosal immune responses to challenge.

The future of long-acting cabotegravir plus rilpivirine therapy: deeds and misconceptions.

HIV infection is currently managed as a chronic disease because of improvements in antiretroviral therapy (ART). Switching to a new regimen is a natural event during long-term therapy to avoid problems related to toxicity, adherence, failure, and potential selection of drug resistance. The development of co-formulations of multiple agents in one pill, and novel drug classes and drugs with a high genetic barrier to resistance have been important in this context. The approval of the long-acting, once-monthly or bimonthly injectable combination of the second-generation strand transfer integrase inhibitor (InSTI), cabotegravir (CAB) together with the non-nucleoside reverse transcriptase inhibitor (NNRTI), rilpivirine (RPV) represents the most recent achievement in the search for potent and convenient ART. Several pivotal trials (such as LATTE-2, ATLAS, FLAIR, and ATLAS-2M) showed the high efficacy and safety of this long-acting formulation used as an induction-maintenance strategy. Few confirmed virological failures (CVF) have been observed. The combination of at least two of the following baseline factors, HIV-1 subtype A6/A1, a body mass index (BMI) ≥30 kg/m2, and RPV resistance-associated mutations, was associated with an increased risk of CVF at week 48. The data indicate that this long-acting therapeutic strategy is attractive and potent; therefore, defining the most appropriate patient for this treatment and how to handle practical issues is warranted.

Decay rate of antiS1/S2 IgG serum levels after 6 months of BNT162b2 vaccination in a cohort of COVID-19-naive and COVID-19-experienced subjects.

Vaccination toward SARS-CoV-2 reduced mortality and 'boosters' are being implemented. We offer scientific contribution about IgG production in the COVID-19 experienced population. From January 2021 to March 2021, 183 residents and staff from the Elderly Nursing Home "San Giuseppe Moscati" who had received two doses of the BNT162b2 vaccine were enrolled. The antibody response was assessed by the DiaSorin LIAISON-CLIA S1/S2® IgG solution. Cutoff levels for response (>39 BAU/mL) and neutralizing activity (>208 BAU/mL) were derived from DiaSorin official data. Serology was assessed before and after the first vaccination, and 2 weeks and 6 months after the second vaccination. Anti-S IgG in COVID-19 experienced, baseline IgG producers spiked after the first vaccination to median 5044 BAU/mL and decayed at 6 months to 2467.4 BAU/mL. Anti-S IgG in COVID-19 experienced, baseline IgG non-producers spiked after the second vaccination to median 1701.7 BAU/mL and decayed at 6 months to 904.8 BAU/mL. Anti-S IgG in COVID-19 naïve subjects spiked after the second vaccination to median 546 BAU/mL and decayed at 6 months to 319.8 BAU/mL. The differences between sequential timepoint levels in each group were statistically significant (p < .0001). Serology analysis revealed different kinetics between COVID-19 experienced subjects depending on baseline response, possibly predicting different IgG persistence in blood.