Itzchak Levy

Objectives: Syphilis reinfection is increasing among men who have sex with men (MSM) living with HIV and is frequently asymptomatic, complicating timely diagnosis and management. Current screening strategies rely on multistep serological algorithms that require confirmation with non-treponemal testing, often delaying clinical decision-making. The chemiluminescent microparticle immunoassay for Treponema pallidum (TP-CMIA) is widely used as an initial screening assay and provides quantitative signal-to-cut-off values; however, it is currently designated for qualitative interpretation. We aimed to evaluate whether longitudinal changes (ie, dynamics) in TP-CMIA values can serve as an early marker of syphilis reinfection and support initial clinical decision-making. Methods: We conducted a retrospective observational study including 179 MSM living with HIV who underwent routine syphilis screening between 2014 and 2024 and had at least two paired treponemal (TP-CMIA) and non-treponemal (rapid plasma reagin (RPR)) test results. Syphilis infection status was classified using an algorithm based on RPR dynamics and Centres for Disease Control guidelines. Absolute and relative changes were analysed between sequential tests. Diagnostic performance was assessed using receiver operating characteristic and precision-recall analyses. Results: Absolute changes in TP-CMIA values demonstrated good diagnostic performance for identifying reinfection, with a receiver operating characteristic area under the curve of 0.84. Performance improved to 0.90–0.95 for first reinfection episodes when prior TP-CMIA values were <21 signal-to-cut-off. Optimised thresholds yielded positive predictive values of 70%–75%, specificity of 99%, and negative predictive values exceeding 98%. Sensitivity increased from 47% overall to 60%–75% under refined conditions. Performance was independent of HIV viral load and CD4 count, while younger age was associated with higher false-positive rates. Conclusions: Longitudinal absolute changes in TP-CMIA values represent a robust early marker of syphilis reinfection among MSM living with HIV, although it is limited when baseline values are high. TP-CMIA dynamics may support earlier recognition of reinfection and inform initial clinical decision-making during serological follow-up.

This retrospective, cross-sectional study assessed the burden of HIV in Israel’s Maccabi Healthcare Services in 2022. Among 2.6 million individuals assessed (lookback period: > 2 decades), 1973 PWH were identified and age-sex-matched (1:5) to 9,865 randomly selected controls without HIV. We compared sociodemographic, clinical characteristics, and healthcare resource utilization (HRU; Jan–Dec 2022) between people with and without HIV and characterized antiretroviral therapy (ART) treatment patterns among PWH (Jan–Dec 2022). Compared to controls, PWH had a higher lifetime prevalence (since 1988; P < 0.001) of several comorbid conditions, including liver disease, chronic kidney disease, any cancer, and hepatitis B and C infections. Additionally, PWH had a higher rate of anxiety and depression (26.2% vs. 13.5%; P < 0.001). PWH showed higher annual HRU than controls, including ~2-fold higher hospitalizations (≥1 new admissions; P < 0.001) and frequent use of emergency, urgent, primary, specialist, and nursing care (P < 0.05). Among 1907 PWH with ≥1 ART prescription, 78.1% had ≥90% coverage in 2022, although 69.1% experienced ART interruption and 7.2% discontinuation, the latter associated with mental health issues. This study recognizes critical gaps in care that could inform strategies to improve clinical outcomes and resource allocation in health systems for PWH.

In Israel, irregular migrants (IMs) living with human immunodeficiency virus (HIV-1) that have no access to regular health insurance are provided with HIV-1-related health coverage under a public–private partnership (PPP) program initiated by the Ministry of Health in 2014. Here we characterized IMs referred to the PPP in 2019–2024 and used a linear mixed-effects model to follow up their CD4 and HIV-1 viral load (VL) counts for a median period of 16 months. Subtypes, resistance mutations and phylogenetic relationships were determined in all cases with viral failure and in selected cases with available blood remains. A total of 231 of 238 referred to the PPP initiated antiretroviral treatment (ART) with nucleoside reverse transcriptase inhibitors (NRTIs) and either non-nucleoside reverse transcriptase inhibitors (NNRTIs, 61.5%, 142/231) or protease inhibitors (PIs, 38.5%, 89/231). Irrespective of the treatment regimen, all these individuals increased their CD4 and decreased their VL trajectories over time (p < 0.001). However, mixed model analysis revealed two classes of CD4 trajectory patterns. Comparison between these two patterns revealed that Class-1 individuals started with lower initial CD4 counts compared to Class-2 individuals (median of 115 cells/mm³, IQR 70–171 compared to median of 312 cells/mm³, IQR 104–510, p < 0.001) and experienced slower recovery compared to Class-2. Most Class-1 individuals originated from Africa (78% vs. 52%, p = 0.016). Treatment failure was observed in 5.6% of all individuals receiving treatment under the program. Sequencing analysis, enabled in 23% of the treated cohort, revealed that the reverse transcriptases (RT) M184V (13%) and K103N (7.4%) were the most prevalent mutations. Conclusively, while treatment was not consistent with current recommendations for first-line therapy, the virological and immunological response of most patients was favorable and the prevalence of cases with resistance mutations was not higher than that identified in people living with HIV-1 who are covered by the national health insurance. Despite the limitations of the PPP, this program may provide a unique therapeutic opportunity for IMs with HIV-1.

This study evaluated how informing clinicians about Clostridioides difficile (CD) carriage affected antibiotic stewardship. A quasi-experimental pre/post design assessed antibiotic use in carriers versus non-carriers. Clinician awareness was associated with reduced antibiotic use, particularly quinolones, among carriers. Findings suggest screening and targeted education enhance stewardship and reduce high-risk antibiotic use.

In May 2022, the most widespread outbreak of sustained transmission of mpox outside of countries historically affected countries in Western and Central Africa occurred. We aimed to examine the personal and clinical experiences of international healthcare workers (HCWs) during this public health emergency. We conducted an international cross-sectional survey study between August and October 2022, examining the experiences and perceptions of HCWs clinically involved in the 2022 mpox response. Respondents were recruited via an international network of sexual health and HIV clinicians responding to mpox and promoted through clinical associations and social media. Survey domains included: clinical workload; preparedness; training and support at work; psychological well-being and vaccination. 725 multi-national healthcare workers across 41 countries were included in the analysis. 91% were physicians specialised in Sexual Health or Infectious Diseases; with 34% (n = 247) of all respondents involved in mpox policy. A substantial proportion of respondents (n = 296, 41%) reported working longer hours during the mpox outbreak, with no concomitant removal of other clinical responsibilities. 30% (n = 218) of respondents reported that they had never heard of mpox before the outbreak and over 25% of the respondents reported that they had misdiagnosed someone initially. This culminated in a high prevalence of moral distress at thirty percent. Less than 9% of HCWs in the region of the Caribbean, Central America and South America had been offered a vaccine as compared to almost one-third in the other regions. Where offered, there were high levels of uptake across all regions. The findings highlight a critical need for addressing the profound gaps in HCW knowledge about re-emerging diseases with pandemic potential. Strengthening the resilience of global health systems and prioritising internationally coordinated approaches to global vaccine deployment is imperative.

In May 2022, the most widespread outbreak of sustained transmission of mpox outside of countries historically affected countries in Western and Central Africa occurred. We aimed to examine the personal and clinical experiences of international healthcare workers (HCWs) during this public health emergency. We conducted an international cross-sectional survey study between August and October 2022, examining the experiences and perceptions of HCWs clinically involved with the 2022 mpox response. Respondents were recruited via an international network of sexual health and HIV clinicians responding to mpox and promoted through clinical associations and social media. Survey domains included: clinical workload; preparedness; training and support at work; psychological well-being and vaccination. 725 multi-national healthcare workers across 41 countries were included in the analysis. 91% were physicians specialised in Sexual Health or Infectious Diseases; with 34% (n=247) of all respondents involved in mpox policy. A substantial proportion of respondents (n=296, 41%) reported working longer hours during the mpox outbreak, with no concomitant removal of other clinical responsibilities. 30% (n=218) of respondents reported that they had never heard of mpox before the outbreak and over 25% of the respondents reported that they had misdiagnosed someone initially. This culminated in a high prevalence of moral distress at 30%. Less than 9% of HCWs in the region of the Caribbean, Central America and South America had been offered a vaccine as compared to almost 1/3 in the other regions. Where offered, there were high levels of uptake across all regions. Our findings highlight a critical need for addressing the profound gaps in HCW knowledge about re-emerging diseases with pandemic potential. Strengthening the resilience of global health systems and prioritising internationally coordinated approaches to global vaccine deployment is imperative.

Despite the progress in contemporary antiretroviral therapy (ART) and the continuous changes in treatment guidelines, virological failure (VF) is still an ongoing concern. The goal of this study was to assess factors related to VF after first-line ART. A longitudinal cohort retrospective study of individuals on first-line ART diagnosed with HIV-1 in 2010–2018 and followed-up for a median of two years was conducted. Demographics, baseline and longitudinal CD4 counts, treatment regimens, adherence and VF were recorded. The Cox proportional hazards regression and mixed models were used. A cohort of 1130 patients were included. Overall, 80% were males and 62% were Israeli-born individuals. Compared to individuals diagnosed in 2010–2014, when treatment was initiated according to CD4 levels, those diagnosed in 2015–2018 were older and had lower baseline CD4 counts. VF was recorded in 66 (5.8%) patients. Diagnosis with CD4 p < 0.001) and non-integrase strand transfer inhibitor regimens (non-INSTI, HR = 1.80, 95%CI:1.01–3.24, p = 0.047) increased VF risk. No impact of baseline resistance was observed. We concluded that the early detection of HIV-1 infection and usage of INSTI-based regimens are recommended to reduce VF.

Purpose of review: Persons living with HIV (PLWH) may have a moderately increased risk of morbidity and mortality from COVID-19 infection, especially if viral load is not controlled and if they are immunosuppressed. Vaccination against SARS-CoV-2 is the most effective measure to prevent morbidity and mortality. However, individuals with HIV/AIDS may have less protection after vaccination. The purpose of this review is to summarize some of the recent studies focused on examining the safety, immunogenicity and effectiveness of anti-SARS-CoV-2 vaccines. Recent findings: The safety of all anti-SARS-CoV-2 vaccines among PLWH is not different from the safety of these vaccines among HIV-negative individuals and is acceptable. PLWH with viral suppression and immune reconstitution (CD4⁺ cell count > 350 cells/μl) may reach almost same immunogenicity such as people without HIV albeit antibody levels and neutralization may decline more rapidly than in people without HIV. PLWH with viremia or immunosuppressed, especially AIDS, have less immunogenicity. Summary: Full vaccination against SARS-CoV-2 is a well tolerated and efficient way to prevent mortality and morbidity from COVID-19 among PLWH and AIDS patients. It is very important to follow recommended booster vaccination for a continuous and prompt immunogenicity.

HIV-1 patients place an economic burden on the health system. The objectives of this study were to estimate the direct HIV-1 costs and cost-related factors of HIV-1 patients in Israel and identify cost predictors. We conducted a retrospective study of randomly selected HIV-1 patients aged ≥18 who visited a large outpatient clinic in 2015 and/or 2019. Yearly costs of physician and nurse visits, antiretroviral therapy (ART) and laboratory tests were calculated in USD using the 2020 purchasing power parities. Associations between disease characteristics and costs were analyzed using univariate and multivariable analysis. The median (IQR) total direct costs per patient per year were USD 12,387 (9813–14,124) and USD 12,835 (11,651–13,970) in 2015 (n = 284) and 2019 (n = 290), respectively. ART accounted for approximately 77% of all direct costs, followed by laboratory tests (20%) and medical visits (3%) in both studied years. Being female (USD +710), first yearly viral load <50 c/mL (+$1984) and ≥20 years with HIV-1 (USD +1056) were independently associated with higher costs. In conclusion, HIV-1 cost was stable in the studied period. Viral load and time since diagnosis were the major determinants associated with HIV-1 costs. ART and laboratory tests accounted for 97% of the costs. Therefore, these factors should be considered when planning future expenditures.