Ellen Vancutsem

The international spread of HIV-1 sub-subtype A6 raises concerns due to its association with contraindications for long-acting injectable formulations of cabotegravir (LA-CAB) and rilpivirine (LA-RPV). This study investigated its increasing proportion in Belgium, assessing transmission dynamics and potential migration links. Additionally, genotypic drug resistance in the Belgian HIV-1 sub-subtype A6 population were analyzed and four automatic subtyping tools were compared. A dataset of 4764 HIV-1 protease and reverse transcriptase (RT) sequences from newly diagnosed, treatment-naïve individuals in Belgium (2013–2022) was analyzed. A combination of phylogenetic analysis and online subtyping tools identified 136 sub-subtype A6 sequences. The increase in the proportion of HIV-1 sub-subtype A6 observed in Belgium since 2020 reflects changing transmission patterns, especially among Belgium-born men having sex with men, and cannot be solely linked to the recent influx of Ukrainian migrants. Of these sub-subtype A6 sequences, less than 10% showed LA-CAB + LA-RPV resistance, mainly due to E138A within RT. HIVdb and ANRS reliably assessed resistance in this therapy-naïve cohort, and HIVdb, COMET, and SmartGene^® produced concordant subtyping results. While algorithm choice has little impact at low resistance prevalence, further research is necessary and HIVdb and ANRS remain more suitable for ongoing clinical and research use.

Purpose To evaluate (1) HIV-1 viral load in pre- and post-processed testicular tissue samples from virally suppressed azoospermic HIV-positive men and (2) the reproductive outcome of the subsequent ICSI cycles. Methods This single-center case series reports on all virally suppressed HIV-positive men who underwent testicular biopsy at our center between 2015 and 2023. Whenever spermatozoa were present, samples underwent washing and viral load assessment in the first and last supernatant fractions. Cryopreservation of the last pellet was performed only if the final supernatant showed undetectable viral load. Embryological and clinical outcomes of subsequent ICSI cycles were evaluated. Results Six virally suppressed azoospermic HIV-positive men (mean age 43.1 ± 6.8 years) underwent seven biopsies, all yielding spermatozoa. All patients had frozen sperm available for ICSI with undetectable viral load following processing. Eight ICSI cycles were performed across six couples, with fertilization and embryo utilization rates of 57.9% (33/57) and 63.6% (21/33). Three fresh single embryo transfers (three couples) resulted in one monozygotic twin delivery. Twelve frozen embryo transfers (five couples) led to four live births and one elective termination. The cumulative live birth rate per couple was 50.0% (3/6). Conclusions We report cryopreservation of testicular tissue with undetectable viral load following sperm processing in virally suppressed HIV-positive men. Therapeutic application of these samples in ICSI-cycles results in successful clinical outcomes.

Background and Objectives: Different COVID‐19 vaccine platforms elicit variable immune responses, influenced by prior infection and booster vaccination. We aimed to compare the humoral immune responses elicited by mRNA and adenoviral vector (Ad‐vector) COVID‐19 vaccines in hospital employees and to assess the possible impact of prior SARS‐CoV‐2 infection on these responses. Methods: We performed a prospective observational cohort study by recruiting employees of the Universitair Ziekenhuis Brussel who were vaccinated with an mRNA or Ad‐vector vaccine. We assessed anti‐spike (S) IgG and neutralising capacity at 1, 6 and 12 months (post‐mRNA booster). Anti‐S and anti‐NCP IgG were measured by chemiluminescent microparticle immunoassay, and neutralising capacity was assessed using Genscript's cPASS. Non‐parametric group comparisons used the Mann–Whitney U test, complemented by multiple linear regression. Results: Following RVR, mRNA‐vaccinated individuals ( n = 380) exhibited higher anti‐S IgG titres and neutralising capacity compared to those who received Ad‐vector vaccines ( n = 200). After the booster, anti‐spike IgG remained higher in mRNA‐vaccinated individuals than in Ad‐vector recipients ( q < 0.001); Ad‐vector vaccinated individuals showed superior neutralising capacity. Natural SARS‐CoV‐2 infection prior to vaccination had varying impact on anti‐S IgG and neutralising capacity, depending on vaccination type and time points. Conclusion: Our findings underscore that both vaccine platforms and prior infections shape the magnitude and quality of the humoral immune response, highlighting the importance of considering priming strategy, booster design and hybrid immunity when optimising COVID‐19 vaccination schedules for durable protection.

This case report describes a 60-year-old female patient suffering from systemic sclerosis, for which she received immunomodulatory drugs. Her first SARS-CoV-2-positive nasopharyngeal sample was obtained in the emergency department, on 31 January 2022. Whole genome sequencing confirmed infection with Omicron BA.1.1. Her hospital stay was long and punctuated by many complications, including admission to the intensive care unit. At the beginning of April 2022, she started complaining of increased coughing, for which another SARS-CoV-2 RT-qPCR test was performed. The latter nasopharyngeal swab showed a strongly positive result. To support the theory of healthcare-associated reinfection, whole genome sequencing was performed and confirmed reinfection with Omicron BA.2. Since this patient was one of ten positive cases in this particular ward, a hospital outbreak investigation was performed. Whole genome sequencing data were available for five of these ten patients and showed a cluster of four patients with ≤2 small nucleotide polymorphisms difference.

HIV-1 pol sequences obtained through baseline drug resistance testing of patients newly diagnosed between 2013 and 2017 were analyzed for genetic similarity. For 927 patients the information on genetic similarity was combined with demographic data and with information on the recency of infection. Overall, 48.3% of the patients were genetically linked with 11.4% belonging to a pair and 36.9% involved in a cluster of ≥3 members. The percentage of early diagnosed (≤4 months after infection) was 28.6%. Patients of Belgian origin were more frequently involved in transmission clusters (49.7% compared to 15.3%) and diagnosed earlier (37.4% compared to 12.2%) than patients of Sub-Saharan African origin. Of the infections reported to be locally acquired, 69.5% were linked (14.1% paired and 55.4% in a cluster). Equal parts of early and late diagnosed individuals (59.9% and 52.4%, respectively) were involved in clusters. The identification of a genetically linked individual for the majority of locally infected patients suggests a high rate of diagnosis in this population. Diagnosis however is often delayed for >4 months after infection increasing the opportunities for onward transmission. Prevention of local infection should focus on earlier diagnosis and protection of the still uninfected members of sexual networks with human immunodeficiency virus (HIV)-infected members.

There is today no gold standard method to accurately define the time passed since infection at HIV diagnosis. Infection timing and incidence measurement is however essential to better monitor the dynamics of local epidemics and the effect of prevention initiatives. Three methods for infection timing were evaluated using 237 serial samples from documented seroconversions and 566 cross sectional samples from newly diagnosed patients: identification of antibodies against the HIV p31 protein in INNO-LIA, SediaTM BED CEIA and SediaTM LAg-Avidity EIA. A multi-assay decision tree for infection timing was developed. Clear differences in recency window between BED CEIA, LAg-Avidity EIA and p31 antibody presence were observed with a switch from recent to long term infection a median of 169.5, 108.0 and 64.5 days after collection of the pre-seroconversion sample respectively. BED showed high reliability for identification of long term infections while LAg-Avidity is highly accurate for identification of recent infections. Using BED as initial assay to identify the long term infections and LAg-Avidity as a confirmatory assay for those classified as recent infection by BED, explores the strengths of both while reduces the workload. The short recency window of p31 antibodies allows to discriminate very early from early infections based on this marker. BED recent infection results not confirmed by LAg-Avidity are considered to reflect a period more distant from the infection time. False recency predictions in this group can be minimized by elimination of patients with a CD4 count of less than 100 cells/mm3 or without no p31 antibodies. For 566 cross sectional sample the outcome of the decision tree confirmed the infection timing based on the results of all 3 markers but reduced the overall cost from 13.2 USD to 5.2 USD per sample. A step-wise multi assay decision tree allows accurate timing of the HIV infection at diagnosis at affordable effort and cost and can be an important new tool in studies analyzing the dynamics of local epidemics or the effects of prevention strategies.

The Belgian HIV epidemic is largely concentrated among men who have sex with men and Sub-Saharan Africans. We studied the continuum of HIV care of those diagnosed with HIV living in Belgium and its associated factors. Data on new HIV diagnoses 2007–2010 and HIV-infected patients in care in 2010–2011 were analysed. Proportions were estimated for each sequential stage of the continuum of HIV care and factors associated with attrition at each stage were studied. Of all HIV diagnosed patients living in Belgium in 2011, an estimated 98.2 % were linked to HIV care, 90.8 % were retained in care, 83.3 % received antiretroviral therapy and 69.5 % had an undetectable viral load (<50 copies/ml). After adjustment for sex, age at diagnosis, nationality and mode of transmission, we found lower entry into care in non-Belgians and after preoperative HIV diagnoses; lower retention in non-Belgians and injecting drug users; higher retention in men who have sex with men and among those on ART. Younger patients had lower antiretroviral therapy uptake and less viral suppression; those with longer time from diagnosis had higher ART uptake and more viral suppression; Sub-Saharan Africans on ART had slightly less viral suppression. The continuum of HIV care in Belgium presents low attrition rates over all stages. The undiagnosed HIV-infected population, although not precisely estimated, but probably close to 20 % based on available survey and surveillance results, could be the weakest stage of the continuum of HIV care. Its identification is a priority along with improving the HIV care continuum of migrants.