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Objective: We evaluated the immunogenicity of a bivalent BA.1 COVID-19 booster vaccine in people with HIV (PWH)., Design: Prospective observational cohort study., Methods: PWH aged ≥45 years received Wuhan-BA.1 mRNA-1273.214 and those <45 years Wuhan-BA.1 BNT162b2. Participants were propensity score-matched 1 : 2 to people without HIV (non-PWH) by age, primary vaccine platform (mRNA-based or vector-based), number of prior COVID-19 boosters and SARS-CoV-2 infections, and spike (S1)-specific antibodies on the day of booster administration. The primary endpoint was the geometric mean ratio (GMR) of ancestral S1-specific antibodies from day 0 to 28 in PWH compared to non-PWH. Secondary endpoints included humoral responses, T-cell responses and cytokine responses up to 180 days post-vaccination., Results: Forty PWH received mRNA-1273.214 ( N  = 35) or BNT162b2 ( N  = 5) following mRNA-based ( N  = 29) or vector-based ( N  = 11) primary vaccination. PWH were predominantly male (87% vs. 26% of non-PWH) and median 57 years [interquartile range (IQR) 53-59]. Their median CD4 + T-cell count was 775 (IQR 511-965) and the plasma HIV-RNA load was <50 copies/ml in 39/40. The GMR of S1-specific antibodies by 28 days post-vaccination was comparable between PWH [4.48, 95% confidence interval (CI) 3.24-6.19] and non-PWH (4.07, 95% CI 3.42-4.83). S1-specific antibody responses were comparable between PWH and non-PWH up to 180 days, and T-cell responses up to 90 days post-vaccination. Interferon-γ, interleukin (IL)-2, and IL-4 cytokine concentrations increased 28 days post-vaccination in PWH., Conclusion: A bivalent BA.1 booster vaccine was immunogenic in well treated PWH, eliciting comparable humoral responses to non-PWH. However, T-cell responses waned faster after 90 days in PWH compared to non-PWH., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Understanding the clinical potency of latency-reversing agents (LRAs) on the HIV-1 reservoir is useful to deploy future strategies. This systematic review evaluated the effects of LRAs in human intervention studies., Methods: A literature search was performed using medical databases focusing on studies with adults living with HIV-1 receiving LRAs. Eligibility criteria required participants from prospective clinical studies, a studied compound hypothesised as LRA, and reactivation or tolerability assessments. Relevant demographical data, LRA reactivation capacity, reservoir size, and adverse events were extracted. A study quality assessment with analysis of bias was performed by RoB 2 and ROBINS-I tools. The primary endpoints were HIV-1 reservoir reactivation after LRA treatment quantified by cell-associated unspliced HIV-1 RNA, and LRA tolerability defined by adverse events. Secondary outcomes were reservoir size and the effect of LRAs on analytical treatment interruption (ATI) duration., Results: After excluding duplicates, 5182 publications were screened. In total 45 publications fulfilled eligibility criteria including 26 intervention studies and 16 randomised trials. The risk of bias was evaluated as high. Chromatin modulators were the main investigated LRA class in 24 studies. Participants were mostly males (90.1%). Where reported, HIV-1 subtype B was most frequently observed. Reactivation after LRA treatment occurred in 78% of studies and was observed with nearly all chromatin modulators. When measured, reactivation mostly occurred within 24 h after treatment initiation. Combination LRA strategies have been infrequently studied and were without synergistic reactivation. Adverse events, where reported, were mostly low grade, yet occurred frequently. Seven studies had individuals who discontinued LRAs for related adverse events. The reservoir size was assessed by HIV-1 DNA in 80% of studies. A small decrease in reservoir was observed in three studies on immune checkpoint inhibitors and the histone deacetylase inhibitors romidepsin and chidamide. No clear effect of LRAs on ATI duration was observed., Conclusion: This systematic review provides a summary of the reactivation of LRAs used in current clinical trials whilst highlighting the importance of pharmacovigilance. Highly heterogeneous study designs and underrepresentation of relevant patient groups are to be considered when interpreting these results. The observed reactivation did not lead to cure or a significant reduction in the size of the reservoir. Finding more effective LRAs by including well-designed studies are needed to define the required reactivation level to reduce the HIV-1 reservoir., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: KSH received travel and conference compensation from Gilead. CR received unrestricted grants for investigator initiated research, advisory board participants, and travel compensation from ViiV and Gilead. All other authors declare no potential competing interests., (© 2023 The Authors.)

Background: The COVIH study is a prospective coronavirus disease 2019 (COVID-19) vaccination study in 1154 people with HIV (PWH), of whom 14% showed reduced antibody levels after primary vaccination. We evaluated whether an additional vaccination boosts immune responses in these hyporesponders., Methods: The primary end point was the increase in antibodies 28 days after additional mRNA-1273 vaccination. Secondary end points included neutralizing antibodies, S-specific T-cell and B-cell responses, and reactogenicity., Results: Of the 66 participants, 40 previously received 2 doses ChAdOx1-S, 22 received 2 doses BNT162b2, and 4 received a single dose Ad26.COV2.S. The median age was 63 years (interquartile range [IQR], 60-66), 86% were male, and median CD4+ T-cell count was 650/μL (IQR, 423-941). The mean S1-specific antibody level increased from 35 binding antibody units (BAU)/mL (95% confidence interval [CI], 24-46) to 4317 BAU/mL (95% CI, 3275-5360) (P < .0001). Of all participants, 97% showed an adequate response and the 45 antibody-negative participants all seroconverted. A significant increase in the proportion of PWH with ancestral S-specific CD4+ T cells (P = .04) and S-specific B cells (P = .02) was observed., Conclusions: An additional mRNA-1273 vaccination induced a robust serological response in 97% of PWH with a hyporesponse after primary vaccination. Clinical Trials Registration. EUCTR2021-001054-57-N., Competing Interests: Potential conflicts of interest. S. J. received grants from the Dutch research council (NWO), European Union Horizon 2020, and the Bill and Melinda Gates Foundation. W. F. W. B. declares reimbursement to institution for participation of patient in trial by GSK. R. D. d. V. is listed as inventor of the fusion inhibitory lipopeptide [SARSHRC-PEG4]2-chol on a provisional patent application. K. C. E. S. received honorariums for advisory boards from Gilead and ViiV. C. R. has received research grants from ViiV, Gilead, ZonMw, AIDSfonds, Erasmus MC, and Health∼Holland; and honorariums for advisory boards from Gilead and ViiV. B. J. A. R. declares research grants from Gilead and MSD; and honorary for advisory boards for AstraZeneca, Roche, Gilead, and F2G. K. B. received research and educational grants from ViiV and Gilead; and consulting fees for advisory boards for ViiV, Gilead, MSD, and AstraZeneca. A. R. received grants from the Bill and Melinda Gates foundation and the Leids Universitair Fonds. All other authors report no potential conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

BackgroundAdequate identification and testing of people at risk for HIV is fundamental for the HIV care continuum. A key strategy to improve timely testing is HIV indicator condition (IC) guided testing.AimTo evaluate the uptake of HIV testing recommendations in HIV IC-specific guidelines in European countries.MethodsBetween 2019 and 2021, European HIV experts reviewed guideline databases to identify all national guidelines of 62 HIV ICs. The proportion of HIV IC guidelines recommending HIV testing was reported, stratified by subgroup (HIV IC, country, eastern/western Europe, achievement of 90-90-90 goals and medical specialty).ResultsOf 30 invited European countries, 15 participated. A total of 791 HIV IC guidelines were identified: median 47 (IQR: 38-68) per country. Association with HIV was reported in 69% (545/791) of the guidelines, and 46% (366/791) recommended HIV testing, while 42% (101/242) of the AIDS-defining conditions recommended HIV testing. HIV testing recommendations were observed more frequently in guidelines in eastern (53%) than western (42%) European countries and in countries yet to achieve the 90-90-90 goals (52%) compared to those that had (38%). The medical specialties internal medicine, neurology/neurosurgery, ophthalmology, pulmonology and gynaecology/obstetrics had an HIV testing recommendation uptake below the 46% average. None of the 62 HIV ICs, countries or medical specialties had 100% accurate testing recommendation coverage in all their available HIV IC guidelines.ConclusionFewer than half the HIV IC guidelines recommended HIV testing. This signals an insufficient adoption of this recommendation in non-HIV specialty guidelines across Europe.

Background: Vaccines can be less immunogenic in people living with HIV (PLWH), but for SARS-CoV-2 vaccinations this is unknown. In this study we set out to investigate, for the vaccines currently approved in the Netherlands, the immunogenicity and reactogenicity of SARS-CoV-2 vaccinations in PLWH., Methods and Findings: We conducted a prospective cohort study to examine the immunogenicity of BNT162b2, mRNA-1273, ChAdOx1-S, and Ad26.COV2.S vaccines in adult PLWH without prior COVID-19, and compared to HIV-negative controls. The primary endpoint was the anti-spike SARS-CoV-2 IgG response after mRNA vaccination. Secondary endpoints included the serological response after vector vaccination, anti-SARS-CoV-2 T-cell response, and reactogenicity. Between 14 February and 7 September 2021, 1,154 PLWH (median age 53 [IQR 44-60] years, 85.5% male) and 440 controls (median age 43 [IQR 33-53] years, 28.6% male) were included in the final analysis. Of the PLWH, 884 received BNT162b2, 100 received mRNA-1273, 150 received ChAdOx1-S, and 20 received Ad26.COV2.S. In the group of PLWH, 99% were on antiretroviral therapy, 97.7% were virally suppressed, and the median CD4+ T-cell count was 710 cells/μL (IQR 520-913). Of the controls, 247 received mRNA-1273, 94 received BNT162b2, 26 received ChAdOx1-S, and 73 received Ad26.COV2.S. After mRNA vaccination, geometric mean antibody concentration was 1,418 BAU/mL in PLWH (95% CI 1322-1523), and after adjustment for age, sex, and vaccine type, HIV status remained associated with a decreased response (0.607, 95% CI 0.508-0.725, p < 0.001). All controls receiving an mRNA vaccine had an adequate response, defined as >300 BAU/mL, whilst in PLWH this response rate was 93.6%. In PLWH vaccinated with mRNA-based vaccines, higher antibody responses were predicted by CD4+ T-cell count 250-500 cells/μL (2.845, 95% CI 1.876-4.314, p < 0.001) or >500 cells/μL (2.936, 95% CI 1.961-4.394, p < 0.001), whilst a viral load > 50 copies/mL was associated with a reduced response (0.454, 95% CI 0.286-0.720, p = 0.001). Increased IFN-γ, CD4+ T-cell, and CD8+ T-cell responses were observed after stimulation with SARS-CoV-2 spike peptides in ELISpot and activation-induced marker assays, comparable to controls. Reactogenicity was generally mild, without vaccine-related serious adverse events. Due to the control of vaccine provision by the Dutch National Institute for Public Health and the Environment, there were some differences between vaccine groups in the age, sex, and CD4+ T-cell counts of recipients., Conclusions: After vaccination with BNT162b2 or mRNA-1273, anti-spike SARS-CoV-2 antibody levels were reduced in PLWH compared to HIV-negative controls. To reach and maintain the same serological responses as HIV-negative controls, additional vaccinations are probably required., Trial Registration: The trial was registered in the Netherlands Trial Register (NL9214). https://www.trialregister.nl/trial/9214., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: All authors have completed the ICMJE disclosure form and declare no competing interests exist directly related to the submitted work Conflicts of interest outside the submitted work CR has received research grants from ViiV, Gilead, ZonMW, AIDSfonds, Erasmus MC, and Health~Holland and honorariums for advisory boards from Gilead and ViiV; WFWB declares reimbursement for participation of patient in trial by GSK to institution. DG and RDdV are supported by the Health~Holland grant EMCLHS20017 co-funded by the PPP Allowance made available by the Health~Holland, Top Sector Life Sciences & Health, to stimulate public–private partnerships. RDdV is listed as inventor of the fusion inhibitory lipopeptide [SARSHRC-PEG4]2-chol on a provisional patent application. VASHD has received research grants from ZonMw, Horizon 2020 – Marie Curie-Sklodowska, Takeda and payments for lectures and advisory boards from Takeda, CSL Behring, Pharming and GSK. KCES received honorariums for advisory boards from Gilead and ViiV. BJAR declares research grants from Gilead and MSD and honorary for advisory boards for Astra Zeneca, Roche, Gilead, F2G all outside the context of this work. RvM received consultancies fees paid to their institution from ViiV; Gilead; MSD, received research grants paid to their institution from ViiV; Gilead All other authors declare hat no competing interests exist.

During COVID-19 lockdown, the in-hospital number of HIV indicator conditions decreased disproportionally compared with other non-COVID-19 diseases, which was accompanied by reduced HIV testing rates, number and proportion of positive HIV tests, and new HIV referrals, with more late presentation after lockdown cessation, indicating a significantly impacted HIV care continuum., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

A C-language software program has been developed for emulating the image enhancement processing of a storage phosphor plate system. This software has been implemented on a VAX 3400 computer. There are 2,100 lines of C-language code in the program. There are seven parameters used to specify the degree of enhancement. The software is being implemented on a single accelerator board.

We have successfully interfaced an advanced microcomputer system to a 47-cm image intensifier for direct digital radiology. Our development effort has included the design and construction of hardware and the implementation of software. The system matrix (spatial resolution) is 1024 X 1024 and contrast resolution is 8 bits deep. A receiver-operator-characteristic analysis comparing conventional and digital laser chest radiographs for the detection of lung nodules demonstrated no statistical difference. Dosimetry measurements identified decreased patient dose. The intensifier-based digital imaging system is being increasingly used for a variety of examinations including IV pyelograms, all kinds of barium studies, and skeletal, trauma, and chest studies. Hard-copy laser-printed digital images with "bones black" are preferred by the radiology staff and have been well accepted by referring clinicians.

The continuing increase in diagnostic examinations using digitally formatted image instrumentation imposes new requirements on the acquisition, display, transmission, recording, and archiving of all diagnostic data. The fabrication decisions and initial clinical testing of a prototype on-line, decentralized digital image management system are described. With this system, raw digital data can be viewed by multiple users as soon as it is acquired by an acquisition node and transmitted to a display node. Radiologists and clinicians have given this system a favorable reception.

The number of diagnostic radiology examinations being performed on digitally formatted imaging equipment is continually increasing. However, most digital data are recorded as analogue images and the films stored in a central file. The dynamic range of raw digital data is lost. Currently, the space and cost requirements for storage of all digital data have discouraged most users from attempting it. This article presents the concepts and describes the requirements and initial fabrication of a system that will capture and retain all digital data using a network of peripheralized image acquisition, display, and storage devices. Any piece of digitally formatted equipment can be interfaced into the system. A real-time computer capability provides that any digital examination can be reviewed at any display station for up to 10 days.

The design and implementation of a digital radiology image management system requires the definition, evaluation, and comparison of appropriate measures of system performance. The mean throughput rate is an important measure of the actual performance of a finished system. The mean throughput rate identifies the transmission of digital information either in bits/second or tasks/second. It is dependent on software, database management, equipment interface designs, number of users and display stations, and communications media. The mean throughput rate can document resource allocation bottlenecks within a given system. A model for estimating the mean throughput rate and its application in helping us design our radiology digital image networks is described.

A study was conducted on the use of an irreversible compression technique, Fourier quantization, to reduce the amount of digital data needed for an image. The effect of image compression was studied in radiographs obtained to diagnose subperiosteal bone resorption. Magnification radiographs of 44 hands were digitized to an array size of 4,096 X 4,096 X 12 bits. Selected subregions containing a single middle phalanx were compressed and reconstructed. A subset of the resultant 12-bit uncompressed and 8-, 7-, and 6-bit compressed images were read by four radiologists whose responses were analyzed with receiver operating characteristic (ROC) techniques. There were 81 images used in the ROC analysis, of which 48 were normal and 33 showed subperiosteal resorption. No statistically significant loss of diagnostic quality was detected for 8- or 7-bit compressed images, with average compression ratios of 16:1 and 28:1, respectively. Diagnostic quality was lost with 6-bit images, with an average compression ratio of 107:1.

This article describes a method for generating gray scale analog hard copy images on ordinary paper using a laser printer system. Operation of the computer-controlled laser printer is described. The cost of the laser printer/paper technology is estimated and compared with the cost of multiformat camera/conventional film systems. Results of an initial clinical evaluation of laser printed paper images are presented.

The apparent advantages of a DIMS are often cited by those involved in medical information-management research. The promise of a high-speed electronic image-management system that could increase a department's patient throughput and improve patient care is most attractive. Every major manufacturer of medical imaging equipment has a group working to develop such systems. Many problems remain to be solved before such systems can be acquired, installed, and made operational. This paper has summarized the significant technical problems yet to be solved.