Use of perioperative telotristat in a patient with carcinoid heart disease.

Summary: Carcinoid heart disease is a rare complication of carcinoid syndrome, resulting in right-sided valvular heart disease and subsequent heart failure due to long-term exposure to vasoactive substances. The management of this condition is complex, often requiring surgical intervention. Current perioperative regimens entail the use of prophylactic somatostatin analogs to prevent carcinoid crisis; however, regimens vary widely among practitioners and evidence supporting their efficacy in this clinical setting is mixed. This case report describes the perioperative management of a 65-year-old man with carcinoid heart disease requiring tricuspid and pulmonary valve replacement surgery. As an adjunct to somatostatin analog therapy, the novel tyrosine hydroxylase inhibitor, telotristat, was initiated preoperatively. This combination resulted in normalization of preoperative urinary 5-HIAA levels. The patient successfully underwent tricuspid and pulmonic valve replacement without evidence of carcinoid crisis. This clinical case is the first published documenting the use of telotristat in the perioperative period in a patient with carcinoid syndrome and carcinoid heart disease and was associated with a good long-term outcome despite the high-risk nature of the case. Learning points: Carcinoid crisis is a life-threatening complication of carcinoid syndrome, resulting in hemodynamic instability, bronchospasm, and arrhythmia. Cardiac surgical patients with carcinoid syndrome present a unique challenge as they are subject to physiologic conditions and medications which can potentiate intraoperative carcinoid crisis. Perioperative management of patients with carcinoid syndrome currently entails the use of prophylactic somatostatin analogs; however, these agents do not prevent carcinoid crisis in all cases. Telotristat, a tryptophan hydroxylase inhibitor, shows promise as an adjunctive therapy to somatostatin analogs to reduce the risk of intraoperative carcinoid crisis.

Radiation Exposure from GEP NET Surveillance.

BACKGROUND: Neuroendocrine tumors (NET) are neoplasms that secrete peptides and neuroamines. For gastroenteropancreatic (GEP) NET, surgical resection represents the only curative option. Ten-year imaging surveillance programs are recommended due to long time-to-recurrence following resection. We performed retrospective chart review evaluating radiation exposure and practice patterns from surveillance of completely resected GEP NET. METHODS: We performed a retrospective cohort study of cases with well-differentiated GEP NET from January 2005 to July 2020. Location of primary, modality of imaging, and duration of follow-up were collected. Dosimetry data was collected to calculate effective dose. RESULTS: 62 cases were included with 422 surveillance scans performed. Cross-sectional imaging was used in 82% and functional imaging was used in 18% of scans. Mean number of scans per year was 1.25 (0.42-3). Mean total effective dose was 56.05 mSv (SD 45.56; 0 to 198 mSv) while mean total effective dose per year was 10.62 mSv (SD 9.35; 0 to 45 mSv). Over the recommended ten years of surveillance the estimated total effective dose was 106 mSv. CONCLUSIONS: Surveillance of completely resected GEP NET results in cumulative radiation doses in the range associated with secondary malignancy development. Strategies to minimize radiation exposure in surveillance should be considered in future guideline development.

Dynamicity of HIV Pre-exposure Prophylaxis Usage Pattern and Association with Executed Adherence in MSM: An Implementation Study in Hong Kong.

Pre-exposure prophylaxis (PrEP) use has been shown to be effective for HIV prevention in men who have sex with men (MSM). PrEP use coverage aside, maintenance of high PrEP adherence is crucial in ensuring the achievement of HIV prevention. In this PrEP implementation study in Hong Kong, we examined the patterns of PrEP use in MSM and evaluated their association with prevention-effective adherence for HIV prevention. In January 2020-June 2021 in Hong Kong, 312 recruited MSM (median 30 years old) were followed up for 1 year, with HIV and creatinine testing, consultation, and PrEP refill. No HIV breakthrough infection was observed. As a measure of prevention-effective adherence, executed adherence (EA) was expressed as the proportion of days with HIV risk that were protected by PrEP and/or condom in 6 months. In 65,585 diary entries of 215 MSM, the median proportion of EA achieved was 89% (IQR 84-93%). Three latent classes of PrEP users were identified by latent class analysis. Taking Class 1 "daily dominant PrEP" (n = 113, 53%) as reference, Class 2 "episodic PrEP" (n = 76, 35%) was adopted by MSM with less sexual activity, had less PrEP refill and lower EA level, while Class 3 "mixed PrEP schedule" (n = 26, 12%) MSM were more sexually active but with a similar EA level. The study findings showed varied and dynamic PrEP usage patterns in the real-world setting. Strategies for promoting adherence are needed to ensure the maintenance of high EA level among PrEP-using MSM especially those on episodic PrEP schedule.

Self-sampled multi-anatomic site testing for uncovering the community burden of undiagnosed Chlamydia trachomatis and Neisseria gonorrhoeae infection in men who have sex with men.

PURPOSE: To detect otherwise undiagnosed asymptomatic sexually transmitted infection (STI), and for estimating prevalence among men who have sex with men (MSM). METHODS: In this community-based study in Hong Kong, adult MSM were recruited. After completion of an online survey, free multi-anatomic sites self-sampling kits (urine specimens, pharyngeal and rectal swabs) for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) tests were delivered to requesting participants. Factors associated with STI positivity were analyzed in logistic regression. RESULTS: From September 2021 to October 2022, 712 MSM were recruited, with 86% aged 18-39, and 16% reported history of chemsex engagement. A majority (81%) had previously undergone HIV testing, 68% had ever tested for STI, and 35% previously diagnosed with STI. Totally 428 (60%) had requested self-sampling kits, and 276 (39%) returned collected samples. Among participants who returned the samples, about half had never been tested in the past and had no history of STI. Overall 21% tested positive for CT and/or NG (CT/NG)-CT positive 16% and NG positive 7%. By anatomic site, 16% of rectal swabs, 7% of pharyngeal swabs, but just 3% of urine specimens were CT/NG positive. The prevalence of CT/NG was not significantly different by history of STI diagnosis and testing. CONCLUSION: Self-sampled STI testing is a potentially useful means for enhancing uptake of screening in MSM in the community, which could uncover otherwise undiagnosed asymptomatic infections. Internet-based self-sampling for STI testing could complement the current clinic-based STI testing for supporting epidemiologic evaluation of STI control in the community.

Diagnostic accuracy of bone scintigraphy imaging for transthyretin cardiac amyloidosis: systematic review and meta-analysis.

BACKGROUND: Bone scintigraphy imaging is frequently used to investigate patients with suspected transthyretin cardiac amyloidosis (ATTR-CM). However, the reported accuracy for interpretation approaches has changed over time. We performed a systematic review and meta-analysis to determine the diagnostic accuracy of visual planar grading, heart-to-contralateral (HCL) ratio, and quantitative analysis of SPECT imaging and evaluate reasons for shifts in reported accuracy. METHODS: We performed a systematic review to identify studies of the diagnostic accuracy of bone scintigraphy for ATTR-CM from 1990 until February 2023 using PUBMED and EMBASE. Studies were reviewed separately by two authors for inclusion and for risk of bias assessment. Summary receiver operating characteristic curves and operating points were determined with hierarchical modeling. RESULTS: Out of a total of 428 identified studies, 119 were reviewed in detail and 23 were included in the final analysis. The studies included a total of 3954 patients, with ATTR-CM diagnosed in 1337 (39.6%) patients and prevalence ranging from 21 to 73%. Visual planar grading and quantitative analysis had higher diagnostic accuracy (.99) than HCL ratio (.96). Quantitative analysis of SPECT imaging had the highest specificity (97%) followed by planar visual grade (96%) and HCL ratio (93%). ATTR-CM prevalence accounted for some of the observed between study heterogeneity. CONCLUSIONS: Bone scintigraphy imaging is highly accurate for identifying patients with ATTR-CM, with between study heterogeneity in part explained by differences in disease prevalence. We identified small differences in specificity, which may have important clinical implications when applied to low-risk screening populations.

Integrating Magnetic-Bead-Based Sample Extraction and Molecular Barcoding for the One-Step Pooled RT-qPCR Assay of Viral Pathogens without Retesting.

Pooling multiple samples prior to real-time reverse-transcription polymerase chain reaction (RT-PCR) analysis has been proposed as a strategy to minimize expenses and boost test throughput during the COVID-19 pandemic. Nevertheless, the traditional pooling approach cannot be effectively deployed in high-prevalence settings due to the need for secondary tests in the case of a positive pool. In this study, we present a pooling test platform with high adaptability and simplicity that allows sample-specific detection of multiple-tagged samples in a single run without the need for retesting. This was accomplished by labeling distinct samples with predefined ID-Primers and identifying tagged pooled samples using one-step RT-PCR followed by melting curve analysis with rationally designed universal fluorescence- and quencher-tagged oligo probes. Using magnetic beads (MBs), nucleic acid targets from different individuals can be tagged and extracted concurrently and then pooled before RT, eliminating the need for extra RNA extraction and separate RT and enzyme digestion steps in the recently developed barcoding strategies. Pools of six samples (positive and negative) were successfully identified by melting temperature values under two fluorescent channels, with a detection sensitivity of 5 copies/µL. We validated the reproducibility of this assay by running it on 40 clinical samples with a hypothetical infection rate of 15%. In addition, to aid the scenario of large-scale pooling tests, we constructed a melting curve autoreadout system (MCARS) for statistical analysis of melting curve plots to eliminate error-prone manual result readout. Our results suggest that this strategy could be a simple and adaptable tool for alleviating existing bottlenecks in diagnostic pooling testing.

Implementation Cascade of a Social Network-Based HIV Self-testing Approach for Men Who Have Sex With Men: Cross-sectional Study.

BACKGROUND: HIV testing is the cornerstone of strategies for achieving the fast-track target to end the AIDS epidemic by 2030. Self-testing has been proven to be an effective health intervention for men who have sex with men (MSM). While social network-based approaches for distributing HIV self-tests are recommended by the World Health Organization, their implementation consists of multiple steps that need to be properly evaluated. OBJECTIVE: This study aimed to assess the implementation cascade of a social network-based HIV self-test approach for reaching MSM who had never undergone testing in Hong Kong. METHODS: This is a cross-sectional study. Seed MSM participants were recruited through different web-based channels, who in turn invited their peers to participate in this study. A web-based platform was set up to support the recruitment and referral process. Participants could request for an oral fluid or a finger-prick HIV self-test, with or without real-time support, after completing a self-administered questionnaire. Referrals could be made upon uploading the test result and passing the web-based training. Characteristics of participants completing each of these steps and their preferences for the type of HIV self-test were evaluated. RESULTS: A total of 463 MSM were recruited, including 150 seeds. Participants recruited by seeds were less likely to have previously been tested for HIV (odds ratio [OR] 1.80, 95% CI 1.06-3.04, P=.03) and have lower confidence in performing self-tests (OR 0.66, 95% CI 0.45-0.99, P=.045). Almost all (434/442, 98%) MSM who completed the questionnaire requested a self-test, of whom 82% (354/434) had uploaded their test results. Participants requesting support were new to self-testing (OR 3.65, 95% CI 2.10-6.35, P<.001) and less confident in carrying out the self-test correctly (OR 0.35, 95% CI 0.22-0.56, P<.001). More than half (216/354, 61%) of the eligible participants initiated the referral process by attempting the web-based training with a passing rate of 93% (200/216). They were more likely to have sought sex partners (OR 2.20, 95% CI 1.14-4.25, P=.02), especially through location-based networking apps (OR 2.13, 95% CI 1.31-3.49, P=.002). They also gave higher usability scores along the implementation cascade (median 81 vs 75, P=.003). CONCLUSIONS: The social network approach was effective in diffusing HIV self-tests in the MSM community and reaching nontesters. Support and option to choose a preferable type of self-test are essential to address users' individual needs when delivering HIV self-tests. A positive user experience throughout the processes along the implementation cascade is vital to transform a tester into a promoter. TRIAL REGISTRATION: ClinicalTrials.gov NCT04379206; https://clinicaltrials.gov/ct2/show/NCT04379206.

Transforming Growth Factor ß Signaling Promotes HIV-1 Infection in Activated and Resting Memory CD4+ T Cells.

Understanding the facilitator of HIV-1 infection and subsequent latency establishment may aid the discovery of potential therapeutic targets. Here, we report the elevation of plasma transforming growth factor ß (TGF-ß) during acute HIV-1 infection among men who have sex with men (MSM). Using a serum-free in vitro system, we further delineated the role of TGF-ß signaling in mediating HIV-1 infection of activated and resting memory CD4+ T cells. TGF-ß could upregulate both the frequency and expression of the HIV-1 coreceptor CCR5, thereby augmenting CCR5-tropic viral infection of resting and activated memory CD4+ T cells via Smad3 activation. The production of live HIV-1JR-FL upon infection and reactivation was increased in TGF-ß-treated resting memory CD4+ T cells without increasing CD4 expression or inducing T cell activation. The expression of CCR7, a central memory T cell marker that serves as a chemokine receptor to facilitate T cell trafficking into lymphoid organs, was also elevated on TGF-ß-treated resting and activated memory CD4+ T cells. Moreover, the expression of CXCR3, a chemokine receptor recently reported to facilitate CCR5-tropic HIV-1 infection, was increased on resting and activated memory CD4+ T cells upon TGF-ß treatment. These findings were coherent with the observation that ex vivo CCR5 and CXCR3 expression on total resting and resting memory CD4+ T cells in combination antiretroviral therapy (cART)-naive and cART-treated patients were higher than in healthy individuals. Overall, the study demonstrated that TGF-ß upregulation induced by acute HIV-1 infection might promote latency reservoir establishment by increasing infected resting memory CD4+ T cells and lymphoid organ homing of infected central memory CD4+ T cells. Therefore, TGF-ß blockade may serve as a potential supplementary regimen for HIV-1 functional cure by reducing viral latency. IMPORTANCE Incomplete eradication of HIV-1 latency reservoirs remains the major hurdle in achieving a complete HIV/AIDS cure. Dissecting the facilitator of latency reservoir establishment may aid the discovery of druggable targets for HIV-1 cure. This study showed that the T cell immunomodulatory cytokine TGF-ß was upregulated during the acute phase of infection. Using an in vitro serum-free system, we specifically delineated that TGF-ß promoted HIV-1 infection of both resting and activated memory CD4+ T cells via the induction of host CCR5 coreceptor. Moreover, TGF-ß-upregulated CCR7 or CXCR3 might promote HIV-1 latent infection by facilitating lymphoid homing or IP-10-mediated viral entry and DNA integration, respectively. Infected resting and central memory CD4+ T cells are important latency reservoirs. Increased infection of these cells mediated by TGF-ß will promote latency reservoir establishment during early infection. This study, therefore, highlighted the potential use of TGF-ß blockade as a supplementary regimen with cART in acute patients to reduce viral latency.

Hepatitis B burden and population immunity in a high endemicity city - a geographically random household epidemiology study for evaluating achievability of elimination.

This study aimed to provide reference for evaluating the achievability of hepatitis B virus (HBV) elimination in a high endemicity city with universal neonatal vaccination in place for over 30 years. Between September 2018 and October 2020, 2085 citizens from 1143 geographically random households in Hong Kong completed a questionnaire and had blood-testing for HBV markers (anti-HBs, HBsAg, anti-HBc, HBeAg). We evaluated the epidemiology and examined factors associated with HBV exposure, vaccination and chronic diseases. The proportion of households with HBsAg positive index participants was 9.2% (95% CI 7.5%-10.9%). The age- and sex-adjusted HBsAg prevalence was 6.3% (95% CI 5.3%-7.4%), compared to >10% in those born in 1960-1970 and among non-local born citizens, and <1% in people born after introduction of neonatal vaccination. Among 155 HBsAg positive participants, 59% were aware of their infection status with 10% on treatment and 10/150 (6.7%) HBeAg positive. More than 40% (872/2064) tested negative for both HBsAg and anti-HBs, contributed by the lack of immunity in older adults and the waning immunity of vaccines. Hong Kong has remained at high-intermediate HBV endemicity state. The moderate level of anti-HBs positivity and very low treatment coverage (10%) among HBsAg positive participants pose challenges for achieving the HBV elimination target.

Low level of dengue infection and transmission risk in Hong Kong: an integrated analysis of temporal seroprevalence results and corresponding meteorological data.

Hong Kong is an Asia-Pacific City with low incidence but periodic local outbreaks of dengue. A mixed-method assessment of the risk of expansion of dengue endemicity in such setting was conducted. Archived blood samples of healthy adult blood donors were tested for anti-dengue virus IgG at 2 time-points of 2014 and 2018/2019. Data on the monthly notified dengue cases, meteorological and vector (ovitrap index) variables were collected. The dengue virus (DENV) IgG seroprevalence of healthy adults in 2014 was 2.2% (95%C.I. = 1.8-2.8%, n = 3827) whereas that in 2018/2019 was 1.7% (95%C.I. = 1.2-2.3%, n = 2320). Serotyping on 42 sera in 2018/2019 showed that 22 (52.4%) were DENV-2. In 2002-2019, importation accounted for 95.3% of all reported cases. By wavelet analysis, local cases were in weak or no association with meteorological and vector variables. Without strong association between local cases and meteorological/vector variables, there was no evidence of increasing level of dengue infection in Hong Kong.

Regular Testing of HIV and Sexually Transmitted Infections With Self-Collected Samples From Multiple Anatomic Sites to Monitor Sexual Health in Men Who Have Sex With Men: Longitudinal Study.

BACKGROUND: Regular HIV and sexually transmitted infection (STI) testing for men who have sex with men (MSM) is an important means of infection prevention, the adoption of which remains suboptimal in the community. OBJECTIVE: On the hypothesis that engagement plays an important role in sexual health monitoring, this study aimed to pilot-test internet-based HIV and STI testing with self-sampling to enhance engagement of MSM with regular testing. METHODS: This 1-year cohort study was conducted on HIV-negative MSM aged 18 years or older. A designated website was set up to enable participants to make appointments for baseline and follow-up visits at 3-monthly intervals. On-site blood sampling was performed for HIV and syphilis tests, along with self-collection of pharyngeal swabs, rectal swabs, and urine samples for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) testing. Full engagement, as defined by having made at least 3 visits over a 6-12 months' follow-up period, was compared with partial engagement in the bivariable logistic regression model. RESULTS: Between August 2019 and October 2020, 204 MSM were recruited, after the exclusion of 2 baseline HIV-positive MSM. The majority (189/204, 92.7%) were Chinese, the median age was 31 (IQR 26-39) years, and 58.0% (116/200) had experience with pre-exposure prophylaxis (PrEP) at baseline. Full engagement (146/204, 71.6%) was associated with incident STI during the follow-ups (odds ratio [OR] 4.23, 95% CI 1.63-10.94), seeking a medical referral after STI detection (OR 10.25, 95% CI 3.25-29.79), and a synchronized schedule of HIV and STI testing with PrEP visits (OR 51.85, 95% CI 19.30-139.34). No incident HIV was detected in the follow-up period. At baseline, the overall STI (CT, NG, or syphilis) prevalence was 30%, with CT at 18%, NG at 13%, and syphilis at 5%. During follow-up, the incidences were 59.08/100 person-years (py) for any STI, 33.05/100 py for CT, 29.86/100 py for NG, and 10.4/100 py for syphilis. The detection rates of CT and NG in urine samples were lower than with pharyngeal swabs and rectal swabs. The scores for convenience, confidence of correct sampling, and accuracy of self-sampling were high (7 to 8 out of 10). CONCLUSIONS: Both baseline prevalence and incidence of STI were high among MSM engaged in regular testing. A high degree of engagement in regular STI and HIV testing was positively associated with incident STI, history of health-seeking behaviors, and perceived convenience of self-sampling. Self-sampling could be introduced as a means of enhancing engagement in regular HIV and STI testing.

Performance of 5-Strand Hamstring Autograft Anterior Cruciate Ligament Reconstruction in the STABILITY Study: A Subgroup Analysis.

BACKGROUND: Anterior cruciate ligament (ACL) reconstructions (ACLRs) with graft diameters <8mm have been shown to have higher revision rates. The 5-strand (5S) hamstring autograft configuration is a proposed option to increase graft diameter. PURPOSE: To investigate the differences in clinical outcomes between 4-strand (4S) and 5S hamstring autografts for ACLR in patients who underwent ACLR alone or concomitantly with a lateral extra-articular tenodesis (LET) procedure. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: Data from the STABILITY study were analyzed to compare a subgroup of patients undergoing ACLR alone or with a concomitant LET procedure (ACLR + LET) with a minimum graft diameter of 8mm that had either a 4S or 5S hamstring autograft configuration. The primary outcome was clinical failure, a composite of rotatory laxity and/or graft failure. The secondary outcome measures consisted of 2 patient-reported outcome scores (PROs)-namely, the ACL Quality of Life Questionnaire (ACL-QoL) and the International Knee Documentation Committee (IKDC) score at 24 months postoperatively. RESULTS: Of the 618 patients randomized in the STABILITY study, 399 (228 male; 57%) fit the inclusion criteria for this study. Of these, 191 and 208 patients underwent 4S and 5S configurations of hamstring ACLR, respectively, with a minimum graft diameter of 8mm. Both groups had similar characteristics other than differences in anthropometric factors-namely, sex, height, and weight, and Beighton scores. The primary outcomes revealed no difference between the 2 groups in rotatory stability (odds ratio [OR], 1.19; 95% CI, 0.77-1.84; P = .42) or graft failure (OR, 1.13; 95% CI, 0.51-2.50; P = .76). There was no significant difference between the groups in Lachman (P = .46) and pivot-shift (P = .53) test results at 24 months postoperatively. The secondary outcomes revealed no differences in the ACL-QoL (P = .67) and IKDC (P = .83) scores between the 2 subgroups. CONCLUSION: At the 24-month follow-up, there were no significant differences in clinical failure rates and PROs in an analysis of patients with 4S and 5S hamstring autografts of ≥8mm diameter for ACLR or ACLR + LET. The 5S hamstring graft configuration is a viable option to produce larger-diameter ACL grafts.

Three-Dose Primary Series of Inactivated COVID-19 Vaccine for Persons Living with HIV, Hong Kong.

In a cohort of persons living with HIV in Hong Kong, surrogate virus neutralization testing for COVID-19 yielded a median level of 89% after the third dose of an inactivated COVID-19 vaccine, compared with 37% after the second dose. These results support using a 3-dose primary series for enhanced immune protection.

Point-of-care hepatitis C reflex testing and treatment referral in methadone clinic settings in Hong Kong-a pilot study.

Objectives: People who inject drugs (PWID) constitute a population group with a high hepatitis C virus (HCV) burden. With the objectives of assessing the HCV prevalence in PWID and determining the proportion requiring treatment who could be linked to care, this study piloted onsite reflex HCV testing at low threshold methadone clinics, with prompt referral of HCV RNA-positive participants for treatment. Methods: This was a prospective study on methadone clinic attendees in Hong Kong. Questionnaires were completed, finger-prick anti-HCV rapid testing was performed, and positive blood samples were collected for laboratory HCV RNA testing. The proportions of participants along the cascade of HCV care were calculated. Results: In 2021-2022, after 14 evening screening sessions at three methadone clinics, 86 of 354 regular attendees (24%) were recruited. The anti-HCV prevalence was 63% (54/86, 95% confidence interval 52-73%), with 78% (42/54) testing positive for HCV RNA and 79% (33/42) successfully referred. Almost all (31/33) referred participants received direct-acting antiviral (DAA) treatment, 94% (29/31) with full treatment compliance; 55% (16/29) of these compliant participants achieved a sustained virological response, while the remainder had not received post-treatment testing. Conclusions: The use of a simplified testing algorithm in the setting of substitution treatment services, incorporating reflex HCV testing, could be an effective strategy for contributing towards the micro-elimination of HCV in PWID.

User Experience and Usability of Neumorphism and Gamification User Interface Designs in an HIV Self-Test Referral Program for Men Who Have Sex With Men: Prospective Open-Label Parallel-Group Randomized Controlled Trial.

BACKGROUND: Digital interventions have been applied for promoting HIV prevention and care among men who have sex with men (MSM). As user interface (UI) design plays a role in determining usability and user experience (UX), the intervention outcome could be affected. OBJECTIVE: In this study, we hypothesized that 2 UI design styles, namely gamification and neumorphism, could impact usability and be differentially preferred by distinct groups of MSM. METHODS: A prospective parallel-group open-label randomized controlled trial was conducted in Hong Kong. Eligible participants were adult MSM recruited by the research team or referred by enrolled participants, who followed instructions for performing an HIV self-test and promoted its use within their social network. Participants were randomized in a 1:1 ratio into either a gamification or neumorphism arm, with primarily visual differences in the UI only. The primary outcome was usability measured by the System Usability Scale (SUS) between the 2 arms. Distinct characteristics of promoters in the 2 arms who gave an SUS score of 80 or above were identified. RESULTS: Of 463 MSM registered in the study, 232 and 231 were randomized to the gamification and neumorphism arms, respectively. Excluding those who did not request a self-test kit, data from 218 and 216 participants in the gamification and neumorphism arms, respectively, were analyzed (totally 434 participants). With a median SUS score of 80 overall, participants in the neumorphism arm gave a higher score (P<.001), with a higher proportion giving a promoter-level SUS score (P=.002). Promoters used social media for sex networking (P=.02), used pre-exposure prophylaxis in the preceding year (P=.006), had higher satisfaction in UI design (P<.001), and had made a self-test referral (P=.04). In general, higher usability was recorded among participants who were confident in performing the HIV self-test (P<.001), and this was associated with a promoter-level SUS score in both arms. While no other personal characteristics were associated with promoters in the neumorphism arm, those in the gamification arm had higher HIV-related knowledge (P=.01), preferred a specific partner body image type (P=.03), and progressed toward peer referral by completing online training (P=.04). CONCLUSIONS: Both gamified and neumorphic UI designs were well-accepted by MSM. UX and satisfaction of UI were both crucial in influencing the willingness of MSM to promote the application by referring their peers in the community to participate. The simplistic visual design of neumorphism conferred a more general acceptance in the community, whereas gamification was preferred in certain MSM subcommunities. Appropriate UI/UX design should be considered when developing digital interventions targeting the MSM community. TRIAL REGISTRATION: ClinicalTrials.gov NCT04379206; https://clinicaltrials.gov/ct2/show/NCT04379206.

Trajectory patterns of SARS-CoV-2 neutralising antibody response in convalescent COVID-19 patients.

Background: The adaptive immune responses of COVID-19 patients contributes to virus clearance, restoration of health and protection from re-infection. The patterns of and the associated characteristics with longitudinal neutralising antibody (NAb) response following SARS-CoV-2 infection are important in their potential association with the population risks of re-infection. Methods: This is a longitudinal study with blood samples and clinical data collected in adults aged 18 or above following diagnosis of SARS-CoV-2 infection. NAb levels were measured by the SARS-CoV-2 surrogate virus neutralisation test (sVNT). Anonymous clinical and laboratory data were matched with surveillance data for each subject for enabling analyses and applying latent class mixed models for trajectory delineation. Logistic regression models were performed to compare the characteristics between the identified classes. Results: In 2020-2021, 368 convalescent patients in Hong Kong are tested for NAb. Their seroconversion occur within 3 months in 97% symptomatic patients, the level of which are maintained at 97% after 9 months. The NAb trajectories of 200 symptomatic patients are classified by the initial response and subsequent trend into high-persistent and waning classes in latent class mixed models. High-persistent (15.5%) class patients are older and most have chronic illnesses. Waning class patients (84.5%) are largely young adults who are mildly symptomatic including 2 who serorevert after 10 months. Conclusions: Characteristic sub-class variabilities in clinical pattern are noted especially among patients with waning NAb. The heterogeneity of the NAb trajectory patterns and their clinical association can be important for informing vaccination strategy to prevent re-infection.

Surrogate neutralization responses following severe acute respiratory syndrome coronavirus 2 vaccination in people with HIV: comparison between inactivated and mRNA vaccine.

OBJECTIVE: People with HIV (PWH) co-infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are at higher odds of severe diseases. Whereas the immunogenicity of mRNA vaccine and adenovirus-vectored vaccine was similar between PWH in stable condition and healthy adults, the effects of inactivated vaccines are not known. DESIGN: Prospective longitudinal observational study in real-world setting. METHODS: Adult PWH in care and planning to receive either inactivated (day 0 and day 28) or mRNA-based (day 0 and day 21) vaccine against SARS-CoV-2 were recruited, with blood samples collected over 6 months for surrogate virus neutralization test (sVNT). Demographic and clinical data including age, sex, CD4 + cell count, and suppressed viral load (SVL) status were transcribed for analyses, by simple and multivariable linear regression models, and multivariable linear generalized estimating equations (GEE). RESULTS: A total of 611 HIV patients, 91% male patients, were recruited, of whom 423 and 184 have received mRNA-based and inactivated vaccine, respectively. The seroconversion rate was 99% for mRNA-based vs, 86% for inactivated vaccine [odds ratio (OR) = 21.56, P  = 0.004]. At 6 months, mRNA-based vaccine continued to give a higher response (94 vs. 57%, P  < 0.001). The temporal pattern varied between the two vaccines. By GEE, mRNA-based vaccine ( B  = 40.59, P  < 0.001) and latest SVL status ( B  = 10.76, P  = 0.01) were positively associated with sVNT level, but not latest CD4 + cell count. CONCLUSION: In HIV patients, inactivated vaccine gave a lower peak and shorter duration of sVNT responses compared with mRNA vaccine. The results suggested that different strategies may be needed in boosting the immunity in anticipation of the emergence of variants in the community.