HBcAb Positivity as a Risk Factor for Missing HIV RNA Undetectability after the 3TC+DTG Switch.

Hepatitis B Core antibody (HBcAb) positivity is the surrogate marker of hepatitis B occult infection. This condition is not a contraindication for switching to two-drug (2DR) antiretroviral therapy; however, the removal of tenofovir may contribute to poor control of HBV replication. A multicentre retrospective cohort study investigated the impact of HBcAb positivity on HIV control in patients switching to a 2DR with Lamivudine and Dolutegravir (3TC-DTG). In this study, a comparison analysis was conducted between HBcAb-positive and -negative PLWH regarding HIV-RNA suppression, considering: (1): Target Not Detected (TND) < 20 cp/mL; (2) Target Detected (TD) < 20 cp/mL; and (3) Detectable > 20 cp/mL and <50 cp/mL and >50 copies/mL. A total of 267 patients on 2DR with 3TC-DTG were included. In comparison to HBcAb-negative, HBcAb-positive patients were older (45 years [35-54]) and had a lower CD4+ nadir (248 vs. 349 cells/mmc, p = 0.007). No difference in the maintenance of virological suppression was present in the two groups of patients before the switch. Although no patient had an HIV-RNA > 20 cp/mL after the switch, significantly fewer HBcAb-positive compared with -negative subjects resulted in TND at 12, 24, and 36 months after the switch: 52 (69.3%) versus 164 (85.4%), p = 0.004, 50 [72.5%] versus 143 [89.9%], p = 0.001, and 30 [66.7%] versus 90 [92.8%], p = 0.001, respectively. HBcAb positivity is associated with an increased risk of suboptimal HIV suppression during the 36 months after 3TC/DTG simplification. This finding reinforces the relevance of the OBI condition in PLWH and raises the issue of careful virological monitoring of such cases.

SARS-CoV-2 Neutralizing Antibodies to B.1 and to BA.5 Variant after Booster Dose of BNT162b2 Vaccine in HIV Patients COVID-Naïve and on Successful Antiretroviral Therapy.

Live virus neutralization is the gold standard to investigate immunity. This prospective observational study aimed to determine the magnitude of response against the original B.1 lineage and against the BA.5 lineage six months after the third BNT162b2 mRNA vaccine dose in patients with HIV infection on successful antiretroviral treatment and no previous SARS-CoV-2 infection. A total of 100 subjects (M/F 83/17, median age 54 years) were included in the analysis: 95 had plasma HIV RNA <40 copies/mL, the median CD4+ T cell count at the administration of the third dose was 580 cells/mm3, and the median nadir CD4+ T cell count was 258 cells/mm3. Neutralizing antibodies (NtAb) against B.1 were detectable in all the subjects, but those to BA.5 were only detected in 88 (p < 0.001). The median NtAb titer to B.1 was significantly higher than that to BA.5 (393 vs. 60, p < 0.0001), and there was a strong positive correlation between the paired measurements (p < 0.0001). Linear regression on a subset of 87 patients excluding outlier NtAb titers showed that 48% of the changes in NtAb titers to BA.5 are related to the changes in value titers to B.1. SARS-CoV-2 variants evolve rapidly, challenging the efficacy of vaccines, and data on comparative NtAb responses may help in tailoring intervals between vaccine doses and in predicting vaccine efficacy.

Impact of Hypogammaglobulinemia on the Course of COVID-19 in a Non-Intensive Care Setting: A Single-Center Retrospective Cohort Study.

Background: Severity and mortality of COVID-19 largely depends on the ability of the immune system to clear the virus. Among various comorbidities potentially impacting on this process, the weight and the consequences of an antibody deficiency have not yet been clarified. Methods: We used serum protein electrophoresis to screen for hypogammaglobulinemia in a cohort of consecutive adult patients with COVID-19 pneumonia, hospitalized in non-intensive care setting between December 2020 and January 2021. The disease severity, measured by a validated score and by the need for semi intensive (sICU) or intensive care unit (ICU) admission, and the 30-day mortality was compared between patients presenting hypogammaglobulinemia (HYPO) and without hypogammaglobulinemia (no-HYPO). Demographics, comorbidities, COVID-19 specific treatment during the hospital stay, disease duration, complications and laboratory parameters were also evaluated in both groups. Results: We enrolled 374 patients, of which 39 represented the HYPO cohort (10.4%). In 10/39 the condition was previously neglected, while in the other 29/39 hematologic malignancies were common (61.5%); 2/39 were on regular immunoglobulin replacement therapy (IgRT). Patients belonging to the HYPO group more frequently developed a severe COVID-19 and more often required sICU/ICU admission than no-HYPO patients. IgRT were administered in 8/39 during hospitalization; none of them died or needed sICU/ICU. Among HYPO cohort, we observed a significantly higher prevalence of neoplastic affections, of active oncologic treatment and bronchiectasis, together with higher prevalence of viral and bacterial superinfections, mechanical ventilation, convalescent plasma and SARS-CoV-2 monoclonal antibodies administration during hospital stay, and longer disease duration. Multivariate logistic regression analysis and Cox proportional hazard regression confirmed the impact of hypogammaglobulinemia on the COVID-19 severity and the probability of sICU/ICU admission. The analysis of the mortality rate in the whole cohort showed no significant difference between HYPO and no-HYPO. Conclusions: Hypogammaglobulinemia, regardless of its cause, in COVID-19 patients hospitalized in a non-intensive care setting was associated to a more severe disease course and more frequent admission to s-ICU/ICU, particularly in absence of IgRT. Our findings emphasize the add-value of routine serum protein electrophoresis evaluation in patients admitted with COVID-19 to support clinicians in patient care and to consider IgRT initiation during hospitalization.

Humoral Response after Two Doses of BNT162b2 mRNA Vaccine Has a Role in Predicting Response after Three Doses That Is Related to Plasma HIV Viremia and Nadir CD4+ Cell Count in HIV-Positive Patients.

We investigated the spike IgG levels of HIV+ patients on antiretroviral therapy six months after they received their second dose (T2) and six months after the third dose (T3) of the BNT162b2 mRNA vaccine, as well as the influence of different levels of plasma HIV viremia of overall CD4+ cell count and nadir value on the humoral time course. One hundred eighty-four patients were enrolled. The median age was 55 years, the median CD4+ cell count was 639 cells/mm3 and the median nadir value was 258 cells/mm3. On the basis of all tests performed during the study period, persistently undetectable plasma HIV RNA (PUD) was found in 66 patients, low-level viremia (LLV) in 57 and ongoing viremia (OV) in 61. Serum levels of IgG antibodies against a trimeric S-protein antigen were tested with DiaSorin Liaison SARS-CoV-2 TrimericS IgG and the response was classified as optimal (>75th percentile), intermediate (50th−25th percentile) and low (<25th percentile). The frequencies of the three different patterns of plasma HIV viremia (PUD, LLV and OV) were comparable in patients with low, intermediate and optimal IgG response evaluated at T2, with no difference in overall CD4+ cell count or nadir count. At T3, 92.9% of patients achieved an optimal response: T2 response proved to be the most important factor in predicting T3 optimal response in patients with LLV and OV.A nadir value ≤ 330 cells/mm3 had 100% sensitivity in predicting a non-optimal response. In conclusion, we demonstrated the persistence of anti-spike IgG, with high serum levels occurring in most patients six months after the third dose of the BNT162b2 mRNA vaccine and a predictive role of humoral response at T2 in subjects with detectable plasma HIV viremia. Immunological alterations related to past immunodeficiency may persist despite immune reconstitution, and the nadir value could be a useful tool for elaborating personalized vaccine schedules.

Comparison between Dexamethasone and Methylprednisolone Therapy in Patients with COVID-19 Pneumonia Admitted to Non-Intensive Medical Units.

(1) Background: Data on different steroid compounds for the treatment of hospitalized COVID-19 (coronavirus disease 2019) patients are still limited. The aim of this study was to compare COVID-19 patients admitted to non-intensive units and treated with methylprednisolone or dexamethasone. (2) Methods: This was a single-center retrospective study that included consecutive patients with COVID-19 hospitalized in medical wards during the second wave of the pandemic. Thirty-day mortality and the need for intensive or semi-intensive care were the main clinical outcomes analyzed in patients receiving methylprednisolone (60 mg/day) compared with dexamethasone (6 mg/day). Secondary outcomes included complication rates, length of hospital stay, and time to viral clearance. (3) Results: Two-hundred-forty-six patients were included in the analysis, 110 treated with dexamethasone and 136 with methylprednisolone. No statistically significant differences were found between the two groups of patients regarding 30-day mortality (OR 1.35, CI95% 0.71-2.56, p = 0.351) and the need for intensive or semi-intensive care (OR 1.94, CI95% 0.81-4.66, p = 0.136). The complication rates, length of hospital stay, and time to viral clearance did not significantly differ between the two groups. (4) Conclusions: In patients hospitalized for COVID-19 in non-intensive units, the choice of different steroid compounds, such as dexamethasone or methylprednisolone, did not affect the main clinical outcomes.

Mycobacterium chimaera infections following cardiac surgery in Treviso Hospital, Italy, from 2016 to 2019: Cases report.

BACKGROUND: An epidemic of Mycobacterium chimaera (M. chimaera) infections following cardiac surgery is ongoing worldwide. The outbreak was first discovered in 2011, and it has been traced to a point source contamination of the LivaNova 3T heater-cooler unit, which is used also in Italy. International data are advocated to clarify the spectrum of clinical features of the disease as well as treatment options and outcome. We report a series of M. chimaera infections diagnosed in Treviso Hospital, including the first cases notified in Italy in 2016. CASE SUMMARY: Since June 2016, we diagnosed a M. chimaera infection in nine patient who had undergone cardiac valve surgery between February 2011 and November 2016. The time between cardiac surgery and developing symptoms ranged from 6 to 97 mo. Unexplained fever, psychophysical decay, weight loss, and neurological symptoms were common complaints. The median duration of symptoms was 32 wk, and the longest was almost two years. A new cardiac murmur, splenomegaly, choroidoretinitis, anaemia or lymphopenia, abnormal liver function tests and hyponatremia were common findings. All the patients presented a prosthetic valve endocarditis, frequently associated to an ascending aortic pseudoneurysm or spondylodiscitis. M. chimaera was cultured from blood, bioprosthetic tissue, pericardial abscess, vertebral tissue, and bone marrow. Mortality is high in our series, reflecting the poor outcome observed in other reports. Three patients have undergone repeat cardiac surgery. Five patients are being treated with a targeted multidrug antimycobacterial regimen. CONCLUSION: Patients who have undergone cardiac surgery in Italy and presenting with signs and symptoms of endocarditis must be tested for M. chimaera.

Desimplification to multi-tablet antiretroviral regimens in human immunodeficiency virus-type 1 infected adults: A cohort study.

BACKGROUND: Highly active antiretroviral therapy (HAART) is provided free of charge to all human immunodeficiency virus (HIV) positive residents in Italy. As fixed dose coformulations (FDCs) are often more expensive in comparison to the same drugs administered separately in a multi-tablet regimen (MTR), we considered a cost-effective strategy involving patients in the switch from their FDCs to corresponding MTRs including generic antiretrovirals. AIM: To verify if this would affect the virological and immunological response in comparison to maintaining the FDC regimens. METHODS: From January 2012 to December 2013, we assessed the eligibility of all the HIV-1 positive adults on stable HAART being treated at our hospital-based outpatient clinic in Treviso, Italy. Participants who accepted to switch from their FDC regimen to the corresponding MTR joined the MTR group, while those who maintained a FDC regimen joined the FDC group. Clinical data, including changes in HAART regimens, respective reasons why and adverse effects, were recorded at baseline and at follow-up visits occurring at weeks 24, 48 and 96. All participants were assessed for virological and immunological responses at baseline and at weeks 24, 48 and 96. RESULTS: Two hundred and forty-three eligible HIV-1 adults on HAART were enrolled: 163 (67%) accepted to switch to a MTR, joining the MTR group, while 80 (33%) maintained their FDCs, joining the FDC group. In a parallel analysis, there were no significant differences in linear trend of distribution of HIV-RNA levels between the two groups and there were no significant odds in favour of a higher level of HIV-RNA in either group at any follow-up and on the overall three strata analysis. In a before-after analysis, both FDC and MTR groups presented no significant differences in distribution of HIV-RNA levels at either weeks 48 vs 24 and weeks 96 vs 24 cross tabulations. A steady increase of mean CD4 count was observed in the MTR group only, while in the FDC group we observed a slight decrease (-23 cells per mmc) between weeks 24 and 48. CONCLUSION: Involving patients in the switch from their FDC regimens to the corresponding MTRs for economic reasons did not affect the effectiveness of antiretroviral therapy in terms of virological response and immunological recovery.

Epidemiology of Strongyloides stercoralis in northern Italy: results of a multicentre case-control study, February 2013 to July 2014.

Strongyloides stercoralis is a soil-transmitted helminth widely diffused in tropical and subtropical regions of the world. Autochthonous cases have been also diagnosed sporadically in areas of temperate climate. We aimed at defining the epidemiology of strongyloidiasis in immigrants and Italians living in three northern Italian Regions. Screening for S. stercoralis infection was done with serology, confirmation tests were a second serological method or stool agar culture. A case-control approach was adopted and patients with a peripheral eosinophil count ≥ 500/mcL were classified as cases. Of 2,701 individuals enrolled here 1,351 were cases and 1,350 controls; 86% were Italians, 48% women. Italians testing positive were in 8% (97/1,137) cases and 1% (13/1,178) controls (adjusted odds ratio (aOR) 8.2; 95% confidence interval (CI): 4.5-14.8), while positive immigrants were in 17% (36/214) cases and in 2% (3/172) controls (aOR 9.6; 95% CI: 2.9-32.4). Factors associated with a higher risk of infection for all study participants were eosinophilia (p < 0.001) and immigration (p = 0.001). Overall, strongyloidiasis was nine-times more frequent in individuals with eosinophilia than in those with normal eosinophil count.

Human and entomological surveillance of West Nile fever, dengue and chikungunya in Veneto Region, Italy, 2010-2012.

BACKGROUND: Since 2010 Veneto region (North-Eastern Italy) planned a special integrated surveillance of summer fevers to promptly identify cases of West Nile Fever (WNF), dengue (DENV) and chikungunya (CHIKV). The objectives of this study were (i) To increase the detection rate of imported CHIKV and DENV cases in travellers from endemic areas and promptly identify potential autochthonous cases.(ii) To detect autochthonous cases of WNF, besides those of West Nile Neuroinvasive Disease (WNND) that were already included in a national surveillance. METHODS: Human surveillance: a traveler who had returned within the previous 15 days from endemic countries, with fever >38°C, absence of leucocytosis (leukocyte count <10,000 µL), and absence of other obvious causes of fever, after ruling out malaria, was considered a possible case of CHIKV or DENV. A possible autochthonous case of WNF was defined as a patient with fever >38°C for <7 days, no recent travel history and absence of other obvious causes of fever. Entomologic surveillance: for West Nile (WNV) it was carried out from May through November placing CDC-CO2 traps in five provinces of Veneto Region, while for DENV and CHIKV it was also performed around residences of viremic cases. RESULTS: Human surveillance: between 2010 and 2012, 234 patients with fever after travelling were screened, of which 27 (11,5%) were found infected (24 with DENV and 3 with CHIKV). No autochthonous case of DENV or CHIKV was detected. Autochthonous patients screened for WNF were 408, and 24 (5,9%) were confirmed cases. Entomologic surveillance: the WNV was found in 10, 2 and 11 pools of Culex pipiens from 2010 to 2012 respectively, in sites of Rovigo, Verona, Venezia and Treviso provinces). No infected Aedes albopictus with DENV or CHIKV was found. CONCLUSIONS: Veneto is the only Italian region reporting WNV human cases every year since 2008. WNV is likely to cause sporadic cases and unforeseeable outbreaks for decades. Including WNF in surveillance provides additional information and possibly an early alert system. Timely detection of DENV and CHIKV should prompt vector control measures to prevent local outbreaks.

[Tuberculous peritonitis: experience in Treviso from 2000 to 2010]. / Peritonite tubercolare: esperienza di Treviso nel decennio 2000-2010.

Peritonitis is an uncommon localization of tuberculosis in Italy; diagnosis and treatment are often difficult and delayed. Fifteen cases, followed by Infectious Diseases Department in Treviso from 2000 to 2010, are described. Mortality and long term complications were absent, in contrast with medical literature. The usefulness of steroid therapy is still uncertain. Other sites of infection were present in 60 percent of patients (pulmonary TB in 47%), urging the clinician to examine the case promptly to determine infectiousness status.

Baseline cellular HIV DNA load predicts HIV DNA decline and residual HIV plasma levels during effective antiretroviral therapy.

Cellular human immunodeficiency virus type 1 (HIV-1) DNA may be considered a marker of disease progression with significant predictive power, but published data on its correlation with plasma HIV RNA levels and CD4 counts in acute and chronic patients are not conclusive. We evaluated a cohort of 180 patients naïve for antiretroviral therapy before the beginning of treatment and after a virological response in order to define the indicators correlated with HIV DNA load decrease until undetectability. The following variables were evaluated as continuous variables: age, CD4 cell count and log(10) HIV DNA level at baseline and follow-up, and baseline log(10) HIV RNA level. Primary HIV infection at the start of therapy, an HIV RNA level at follow-up of <2.5 copies/ml, origin, gender, and transmission risk were evaluated as binary variables. The decline of HIV DNA values during effective therapy was directly related to baseline HIV DNA and HIV RNA values, to an increase in the number of CD4 cells, and to the achievement of an HIV RNA load of <2.5 copies/ml. An undetectable cellular HIV DNA load was achieved by 21.6% of patients at the follow-up time point and correlated significantly with lower baseline cellular HIV DNA values and with being in the primary stage of infection when therapy started. In conclusion, early treatment facilitated the achievement of undetectable levels of plasma viremia and cellular HIV DNA and a better recovery of CD4 lymphocytes. HIV DNA levels before and during highly active antiretroviral therapy may be used as a new tool for monitoring treatment efficacy.

Progressive disseminated histoplasmosis among human immunodeficiency virus-infected patients from West-Africa: report of four imported cases in Italy.

We report four imported cases of progressive disseminated histoplasmosis (PDH) due to Histoplasma capsulatum variety capsulatum in Human Immunodeficiency Virus-infected patients from West Africa. This report highlights the need to consider diagnosis of PDH among patients with acquired immunodeficiency syndrome who originate from West Africa and present with a prolonged febrile illness and very low CD4 count.