Differences in integrated assessment and management of non-communicable diseases (NCDs) for people with HIV across the WHO European region.

OBJECTIVES: We aimed to assess the extent of integration of non-communicable disease (NCD) assessment and management in HIV clinics across Europe. METHODS: A structured electronic questionnaire with 41 multiple-choice and rating-scale questions assessing NCD assessment and management was sent to 88 HIV clinics across the WHO European Region during March-May 2023. One response per clinic was collected. RESULTS: In all, 51 clinics from 34 countries with >100 000 people with HIV under regular follow-up responded. Thirty-seven clinics (72.6%) reported shared NCD care responsibility with the general practitioner. Systematic assessment for NCDs and integration of NCD management were common overall [median agreement 80%, interquartile range (IQR): 55-95%; and 70%, IQR: 50-88%, respectively] but were lowest in central eastern and eastern Europe. Chronic kidney disease (median agreement 96%, IQR: 85-100%) and metabolic disorders (90%, IQR: 75-100%) were regularly assessed, while mental health (72%, IQR: 63-85%) and pulmonary diseases (52%, IQR: 40-75%) were less systematically assessed. Some essential diagnostic tests such as glycated haemoglobin (HbA1c) for diabetes (n = 38/51, 74.5%), proteinuria for kidney disease (n = 30/51, 58.8%) and spirometry for lung disease (n = 11/51, 21.6%) were only employed by a proportion of clinics. The most frequent barriers for integrating NCD care were the lack of healthcare workers (n = 17/51, 33.3%) and lack of time during outpatient visits (n = 12/51, 23.5%). CONCLUSION: Most HIV clinics in Europe systematically assess and manage NCDs. People with HIV appear to be screened more frequently than the general population at the same age. There are, however, larger gaps among eastern European clinics in general and for clinics in all regions related to mental health, pulmonary diseases and the employment of some essential diagnostic tests.

Dual anti-viral treatment for persistent COVID-19 in immunocompromised hemato-oncological patients is associated with a favorable prognosis and minor side effects.

In hemato-oncological patients, COVID-19 can present as a persistent infection with ongoing symptoms and viral replication over a prolonged period of time. Data are scarce on the preferred treatment options for these patients. We describe our experience with a five-day course of dual anti-viral treatment with remdesivir and nirmatrelvir/ritonavir for hemato-oncological immunocompromised patients with persistent COVID-19. Fifteen patients with a history of lymphoma, CLL, and MM were included. Eight were male, median age was 74. All patients had an immediate clinical and virological response. In 73 % of patients, PCR for SARS-CoV-2 became negative at the end of treatment and the rest had an increase in PCR cycle threshold (CT) values, with a median increase of 6 cycles. After a follow-up of three months, 60 % of patients remained in full clinical and virological remission. None required invasive mechanical ventilation or died. The side effects we observed, neutropenia, lactatemia and elevated transaminases, were mild and almost all transient in nature. We conclude that dual anti-viral treatment appears to be a valid treatment option for persistent COVID-19.

Rate and predictors of blood culture positivity after antibiotic administration: a prospective single-center study.

PURPOSE: Blood culture obtainment prior to antibiotic administration, in patients with suspected infection, is considered the best practice in international guidelines. However, there is little data regarding the effect of a single dose of antibiotics on blood culture sterilization. METHODS: We conducted a prospective study, enrolling consecutive patients with suspected infection, hospitalized in an internal medicine ward between December 2019 and January 2023. Included patients had a positive blood culture prior to antibiotic administration and a set of blood cultures taken within 24 h after a single dose of antibiotics. The rate of patients with pathogen isolation after antibiotic administration was assessed. Logistic regression was performed to examine factors associated with blood culture positivity. RESULTS: A total of 155 patients were recruited for the study of which 131 (50.8% female 77.5 ± 13.4 years) met the inclusion criteria. The overall rate of patients with a positive blood culture after a single dose of antibiotics was 42.0% (55/131 patients). Increasing time between antibiotic administration and post-antibiotic culture was an independent predictor for blood culture sterilization (odds ratio 0.89 [95% confidence interval, 0.83-0.97; p = 0.006] for every 60 min). Blood culture volume was an independent predictor for blood culture positivity in a sensitivity analysis which included 82 patients (OR = 1.26 [95% CI 1.03-1.57] for every 1 ml increase; p = 0.024). CONCLUSION: Blood culture positivity is reduced by antimicrobial therapy but remains high after a single dose of antibiotics. If cultures are not obtained prior to antibiotic administration, they should be obtained as soon as possible afterwards.

Prolonged survival of a patient with active MDR-TB HIV co-morbidity: insights from a Mycobacterium tuberculosis strain with a unique genomic deletion.

Coinfection of HIV and multidrug-resistant tuberculosis (MDR-TB) presents significant challenges in terms of the treatment and prognosis of tuberculosis, leading to complexities in managing the disease and impacting the overall outcome for TB patients. This study presents a remarkable case of a patient with MDR-TB and HIV coinfection who survived for over 8 years, despite poor treatment adherence and comorbidities. Whole genome sequencing (WGS) of the infecting Mycobacterium tuberculosis (Mtb) strain revealed a unique genomic deletion, spanning 18 genes, including key genes involved in hypoxia response, intracellular survival, immunodominant antigens, and dormancy. This deletion, that we have called "Del-X," potentially exerts a profound influence on the bacterial physiology and its virulence. Only few similar deletions were detected in other non-related Mtb genomes worldwide. In vivo evolution analysis identified drug resistance and metabolic adaptation mutations and their temporal dynamics during the patient's treatment course.

Humoral and Cellular Immune Responses of People Living With Human Immunodeficiency Virus After 3 Doses of Messenger RNA BNT162b2 Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine: A Prospective Cohort Study.

Background: Recent studies have shown good serological and cellular immune responses in people living with human immunodeficiency virus (PLWH) after receipt of 2 doses of messenger RNAA (mRNA) severe acute respiratory syndrome coronavirus 2 vaccine. Data are missing regarding the response after 3 vaccine doses. Methods: We followed up a group of PLWH who received 3 doses of the mRNA BNT162b2 vaccine and for whom data of humoral immune response after 2 vaccine doses were available. Patients provided a blood sample 4-6 months after the booster dose. The aim of the study was to measure the serological and cellular response after the third dose and to evaluate factors associated with the vaccine response. Results: Fifty patients have provided a serum sample for serological evaluation after the booster. The anti-receptor-binding domain (RBD) immunoglobulin (Ig) G titers were higher after the booster with a median delta of 3240 arbitrary units/mL. The median CD4+ T-cell count was 660/µL (interquartile range, 515-958/µL) and had no influence on the antibody level. Factors associated with lower delta included higher CD8+ T-cell count (P = .02) and longer time between the third dose and the blood test (P = .01). Higher anti-RBD IgG titer after the second vaccine (P = .03), as well as a longer interval between second and third doses (P = .031) were associated with higher delta. There was no increase in the median number of activated interferon γ+ and tumor necrosis factor α+ CD4+ T cells after the booster (n = 8). Conclusions: The anti-RBD IgG level after 3 doses of mRNA BNT162b2 vaccine was higher than the level after 2 doses, suggesting additional value of the booster. Cellular response did not further increase after a booster.

Safety and outcomes of an early discharge strategy with oxygen home therapy in stable severe COVID-19 patients.

BACKGROUND: COVID-19 disease leads to prolonged hospitalisations and adverse outcomes. We describe our strategy for routine early discharge of severe COVID-19 patients with home oxygen during the Delta variant surge. METHODS: Our strategy included COVID-19 patients requiring oxygen support via nasal cannula, with stabilised but not yet improved respiration (intervention group), that followed strict criteria. Severe COVID-19 patients discharged after improved respiration were considered the control group for comparison. Outcomes included readmissions from active COVID-19 and 30-day mortality. RESULTS: The intervention group included 129 patients, and the control 150. The groups' baseline characteristics were similar, although the control group had more advanced COVID-19 severity. Among the intervention group, 23 (17.8%) had readmissions secondary to active COVID-19, compared to none in the control group. The 30-day mortality rate was similar between the groups (5% vs. 7%). The intervention led to a shorter hospital stay [median 3 days (IQR 2-4) vs. 6 days (IQR 4-9), p < .01], while a very short hospitalisation was associated with readmissions (2.8 vs. 3.5 days, p = .02). A subsequent critical disease or death after the intervention occurred in old (81 years), multimorbid (3.4 ± 1.4) patients with a high percentage of acute kidney injury during their first hospitalisation (50%). CONCLUSIONS: Our discharge strategy led to a short hospital stay, a high readmission rate, and similar long-term outcomes. Considering the difference in disease severity before discharge, this intervention cannot be considered safe for our study population. Correct patient selection is crucial to ensure patient safety when considering early discharge.

Mpox Presenting as Proctitis in Men Who Have Sex With Men.

In our cohort of 70 patients of men who have sex with men (MSM) with mpox, more than one-third presented with proctitis. In two-thirds of proctitis patients, there was no typical rash upon presentation, and in one-fifth, there was no rash at all, making the diagnosis a challenge. A rectal swab for mpox polymerase chain reaction (PCR) can be diagnostic.

Changes in body mass index and clinical outcomes after initiation of contemporary antiretroviral regimens.

BACKGROUND: Weight gain is becoming increasingly prevalent amongst people with HIV (PWH) receiving contemporary antiretroviral treatment. We investigated BMI changes and clinical impact in a large prospective observational study. METHODS: PWH aged ≥18 years were included who started a new antiretroviral (baseline) during 2010-2019 with baseline and ≥1 follow-up BMI assessment available. Rates of clinical outcomes (cardiovascular disease [CVD], malignancies, diabetes mellitus [DM] and all-cause mortality) were analysed using Poisson regression to assess effect of time-updated BMI changes (>1 kg/m 2 decrease, ±1 kg/m 2 stable, >1 kg/m 2 increase), lagged by 1-year to reduce reverse causality. Analyses were adjusted for baseline BMI plus key confounders including antiretroviral exposure. RESULTS: 6721 PWH were included; 72.3% were male, median age 48 years (interquartile range [IQR] 40-55). At baseline, 8.4% were antiretroviral-naive, and 5.0% were underweight, 59.7% healthy weight, 27.5% overweight, and 7.8% were living with obesity. There was an 8.2% increase in proportion of overweight and 4.8% in obesity over the study period (median follow-up 4.4 years [IQR 2.6-6.7]).100 CVDs, 149 malignancies, 144 DMs, and 257 deaths were observed with incidence rates 4.4, 6.8, 6.6, 10.6 per 1000 person-years of follow-up, respectively. Compared to stable BMI, >1 kg/m 2 increase was associated with increased risk of DM (adjusted incidence rate ratio [IRR]: 1.96, 95% confidence interval [CI]: 1.36-2.80) and >1 kg/m 2 decrease with increased risk of death (adjusted IRR: 2.33, 95% CI: 1.73-3.13). No significant associations were observed between BMI changes and CVD or malignancies. CONCLUSIONS: A BMI increase was associated with DM and a decrease associated with death.

Associations of vaccine status with characteristics and outcomes of hospitalized severe COVID-19 patients in the booster era.

BACKGROUND: The resurgence of COVID-19 cases since June 2021, referred to as the fourth COVID-19 wave, has led to the approval and administration of booster vaccines. Our study aims to identify any associations between vaccine status with the characteristics and outcomes of patients hospitalized with severe COVID-19 disease. METHODS: We retrospectively reviewed all COVID-19 patients admitted to a large tertiary center between July 25 and October 25, 2021 (fourth wave in Israel). Univariant and multivariant analyses of variables associated with vaccine status were performed. FINDINGS: Overall, 349 patients with severe or critical disease were included. Patients were either not vaccinated (58%), had the first two vaccine doses (35%) or had the booster vaccine (7%). Vaccinated patients were significantly older, male predominant, and with a higher number of comorbidities including diabetes, hyperlipidemia, ischemic heart disease, heart failure, immunodeficient state, kidney disease and cognitive decline. Time from the first symptom to hospital admission was longer among non-vaccinated patients (7.2 ± 4.4 days, p = 0.002). Critical disease (p<0.05), admissions to the intensive care unit (p = 0.01) and advanced oxygen support (p = 0.004) were inversely proportional to the number of vaccines given, lowest among the booster vaccine group. Death (20%, p = 0.83) and hospital stay duration (8.05± 8.47, p = 0.19) were similar between the groups. CONCLUSION: Hospitalized vaccinated patients with severe COVID-19 had significantly higher rates of most known risk factors for COVID-19 adverse outcomes. Still, all disease outcomes were similar or better compared with the non-vaccinated patients.

SARS-CoV-2 Humoral and Cellular Immune Responses of Patients With HIV After Vaccination With BNT162b2 mRNA COVID-19 Vaccine in the Tel-Aviv Medical Center.

Background: Little is known about vaccine efficacy and sustainability among people with HIV (PWH). We estimated humoral and cellular immune responses postvaccination with BNT162b2 mRNA coronavirus disease 2019 (COVID-19) vaccine among PWH in Tel-Aviv Medical Center. Methods: The vaccine humoral response was evaluated by measuring immunoglobulin G (IgG) titers of antispike receptor-binding domain antibodies (anti-RBD IgG). Cellular response was assessed by stimulating donor peripheral blood mononuclear cells with pooled complete S-peptide mix. Results: One hundred thirty-six PWH who completed 2 doses of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine were tested for anti-RBD IgG and compared with 61 vaccinated health care workers (HCWs). The antibody titers were similar between the groups (median, 118 BAU/mL for PWH and 101.4 BAU/mL for HCWs; P = .231), although the mean time from second vaccine was 4.5 months in PWH and 6.7 months in HCWs (P < .0001). Longer time from second vaccine dose was associated with decreased antibody level, as were CD4 counts <300 cells/µL compared with higher CD4 counts (25.1 BAU/mL vs 119.3 BAU/mL, respectively; P = .047). There was no difference in cellular immune response between vaccinated PWH, convalescent unvaccinated PWH, and vaccinated HCWs. Conclusions: The humoral immune response of PWH was comparable to that of HCWs after BNT162b2 mRNA vaccination. Cellular immune response did not differ between vaccinated PWH, convalescent PWH, and vaccinated HCWs. PWH with CD4 counts <300 cells/µL (n = 9) had lower antibody titers compared with patients with counts >300 cells/µL (n = 127).

Clinical features and outcomes of bacteremic and non-bacteremic Campylobacteriosis: a case-control study.

PURPOSE: Campylobacter bloodstream infection (C-BSI) is uncommon, and its clinical significance is unclear. The aim of the study was to determine risk factors and clinical outcomes associated with Campylobacter BSI. METHODS: We performed a single center retrospective case-control study comparing patients with C-BSI (cases) and patients with nonbacteremic Campylobacter enteritis (controls), from January 2007 through June 2020. Case and control patients were matched by age and sex at a ratio of 1:2. Demographic, clinical, and microbiological characteristics were compared between groups. RESULTS: We identified 76 patients with C-BSI and matched them with 149 nonbacteremic patients with Campylobacter enteritis. Rates of C-BSI increased tenfold in 2014 following the introduction of BacTAlert FA/FN Plus blood culture bottles. Baseline variables significantly associated with C-BSI on multivariable logistic regression were fever, absence of diarrhea and recent exposure to antibiotics. Compared with controls, C-BSI was associated with higher 30-day mortality (12% vs. 2%, P = 0.003), more frequent need for intensive care (6.6% vs. 1.2%, P = 0.032) and longer hospital stay (median, 5 days vs. 3 days, P = 0.003). There was a high proportion of immunocompromised patients in both groups (55%). CONCLUSIONS: C-BSI is identified with increasing frequency, reflecting both changes in epidemiology and improved sensitivity of blood culture systems. Our findings indicate that detection of Campylobacter spp. in blood culture is associated with significantly higher rates of death and other adverse outcomes.

Emergence of Mycobacterium canariasense infections in central Israel.

In 2018, Mycobacterium canariasense bloodstream infection was diagnosed in Israel. Further investigation had identified additional five cases in three medical centers, including isolates from blood (1), cornea (1), and sputum (3). Isolates were susceptible to all the antimicrobial tested. All but one isolate was related by whole-genome phylogeny.

Prevalence and Outcomes for Heavily Treatment-Experienced Individuals Living With Human Immunodeficiency Virus in a European Cohort.

BACKGROUND: Although antiretroviral treatments have improved survival of persons living with HIV, their long-term use may limit available drug options. We estimated the prevalence of heavily treatment-experienced (HTE) status and the potential clinical consequences of becoming HTE. SETTING: EuroSIDA, a European multicenter prospective cohort study. METHODS: A composite definition for HTE was developed, based on estimates of antiretroviral resistance and prior exposure to specific antiretroviral regimens. Risks of progressing to clinical outcomes were assessed by Poisson regression, comparing every HTE individual with 3 randomly selected controls who never became HTE. RESULTS: Of 15,570 individuals under follow-up in 2010-2016, 1617 (10.4%, 95% CI: 9.9% to 10.9%) were classified as HTE. 1093 individuals became HTE during prospective follow-up (HTE incidence rate 1.76, CI: 1.66 to 1.87 per 100 person-years of follow-up). The number of HTE individuals was highest in West/Central Europe (636/4019 persons, 15.7%) and lowest in East Europe (26/2279 persons, 1.1%). Although most HTE individuals maintained controlled viral loads (<400 copies/mL), many had low CD4 counts (≤350 cells/µL). After controlling for age, immunological parameters and pre-existing comorbidities, HTE status was not associated with the risk of new AIDS (adjusted incidence rate ratio, aIRR 1.44, CI: 0.86 to 2.40, P = 0.16) or non-AIDS clinical events (aIRR 0.96, CI: 0.74 to 1.25, P = 0.77). CONCLUSIONS: HTE prevalence increased with time. After adjusting for key confounding factors, there was no evidence for an increased risk of new AIDS or non-AIDS clinical events in HTE. Additional therapeutic options and effective management of comorbidities remain important to reduce clinical complications in HTE individuals.

Single Dose of Doxycycline for the Prevention of Tick-borne Relapsing Fever.

The current postexposure prophylaxis regimen for tick-borne relapsing fever (TBRF) consists of 5 days' doxycycline. In this observational study of 77 spelunkers at high risk for TBRF, a single dose of 100 mg doxycycline taken up to 72 hours after exposure to ticks was 100% effective in preventing the disease.

Immunogenicity of Sci-B-Vac (a Third-Generation Hepatitis B Vaccine) in HIV-Positive Adults.

BACKGROUND: Guidelines recommend hepatitis B virus (HBV) vaccination of all adults positive for human immunodeficiency virus (HIV). Immune responses to single-antigen HBV vaccine among HIV-positive patients are low when compared with HIV-negative adults. Sci-B-Vac™ is a recombinant third-generation HBV that may be advantageous in this population. OBJECTIVES: To examine the immune responses to Sci-B-Vac among HIV-positive adults. METHODS: We conducted a prospective cohort study involving HIV-positive adults who had negative HBV serology (HBSAg, HBSAb, HBcoreAb). Sci-B-Vac at 10 µg/dose was administered intramuscularly upon recruitment and after 1 and 6 months. HBSAb levels were checked 1 month after each dose; a level > 10 mlU/ml was considered protective. Data regarding age, gender, CD4 level, and viral load were collected. RESULTS: The study group comprised 31 patients. Average CD4 count was 503 ± 281 cells/ml, and average viral load was 44 copies/ml. Median interquartile range (IQR) HBVAb titers after the first, second and third immunizations were 0 (0, 3.5), 30 (6, 126) and 253 (81, 408) mlU/ml. Significant titer elevations were found between the second and third immunizations (P = 0.0003). The rate of patients considered protected was 16% after the first, 65% after the second (P < 0.0001), and 84% after the third dose (P = 0.045). No adverse events were reported. More patients under the age of 40 years responded to the first immunization (28% vs. 0%, P = 0.038). CD4 level had no influence on immunization rates. CONCLUSIONS: Sci-B-Vac might achieve better immunization rates among HIV-positive adults compared to the single-antigen vaccine and thus deserves further evaluation in a randomized, double-blind study in this population.

C-reactive protein serum levels as an early predictor of outcome in patients with pandemic H1N1 influenza A virus infection.

BACKGROUND: Data for predicting which patients with pandemic influenza A (H1N1) infection are likely to run a complicated course are sparse. We retrospectively studied whether the admission serum C-reactive protein (CRP) levels can serve as a predictor of illness severity. METHODS: Included were all consecutive adult patients who presented to the emergency department (ED) between May-December, 2009 with a flu-like illness, a confirmed diagnosis of pandemic influenza A (H1N1) infection and a serum CRP level measured within 24 hours of presentation. Patients with a proven additional concurrent acute illness (e.g., bacteremia) were excluded. We used the ROC curve analysis, Kaplan-Meier curves and the Cox proportional hazard model to evaluate the predictive ability of CRP as a prognostic factor. RESULTS: Seventeen (9%) of the 191 enrolled patients were admitted to the intensive care unit (ICU), of whom eight (4%) required mechanical ventilation and three (2%) died. The median admission serum CRP levels were significantly higher among patients who required subsequent ICU care and mechanical ventilation than among patients who did not (123 mg/L and 112 mg/L vs. 40 mg/L, p < .001 and 43 mg/L, p = .017, respectively). A Cox proportional hazard model identified admission serum CRP levels and auscultatory findings over the lungs as independent prognostic factors for ICU admission. Admission serum CRP levels were the only independent prognostic factor for mechanical ventilation. Thirty days after presenting to the ED, none of the patients with admission serum CRP level <28 mg/L (lower tertile) required either ICU admission or mechanical ventilation. At the same time point, 19% of the patients with admission serum CRP level ≥70 mg/L (upper tertile) needed to be admitted to the ICU and 8% of the same upper tertile group required mechanical ventilation. The differences in the rates between the lower vs. upper tertile groups were significant (Log-Rank p < .001 for ICU and p < .024 for mechanical ventilation). CONCLUSIONS: In our study group, serum CRP levels obtained in the early ED admission stage from patients presenting with pandemic H1N1 influenza A infection were found to serve as a useful gauge for predicting disease course and assisting in patient management.