HIV-related public stigma in the era of "Undetectable = Untransmittable": a population-based study in Hong Kong.

BACKGROUND: While global efforts are increasingly relying upon biomedical advancements such as antiretroviral therapy and pre-exposure prophylaxis (PrEP) to end the HIV epidemic, HIV-related stigma remains a concern. This study aimed to assess the general public's awareness and perception of "Undetectable = Untransmittable" (U = U) and PrEP, and the patterns of public stigma towards people living with HIV (PLWH) and their determinants in an Asian Pacific city. METHODS: A population-based, self-administrated online survey was conducted between 10-20 March 2023. All adults aged ≥ 18 years and currently living in Hong Kong were eligible. Participants' socio-demographic characteristics, awareness and perception of U = U and PrEP, as well as HIV-related stigma drivers, experience and practices were collected. Latent class analysis was used to delineate population subgroups based on their stigma profiles as reflected by 1.) fear of infection, 2.) concern about socioeconomic ramification of the disease, 3.) social norm enforcement, 4.) perceived stigma in the community, and 5.) stigmatising behaviours and discriminatory attitudes. Memberships of identified subgroups were then correlated with sociodemographic factors, awareness and perception of U = U and PrEP, using multinominal logistic regression. RESULTS: Responses from a total of 3070 participants (55% male; 79% aged 18-54) were analysed. A majority, 69% and 81%, indicated that they had never heard of U = U and PrEP respectively, and only 39-40% of participants perceived these to be effective in protection from HIV. Four distinct subgroups were identified, namely "Low stigma" (37%), "Modest stigma" (24%), "Moderate stigma" (24%), and "High stigma" (15%). Compared with "Low stigma", lack of awareness of and/or negative perceptions towards U = U and/or PrEP, not knowing any PLWH were associated with increased odds of higher stigma group membership. Lower educational level and not in employment were associated with increased odds of membership in "Moderate stigma" and "High stigma". While older people were more likely to belong to "High stigma", female were more likely to belong to "Moderate stigma". "Modest stigma" included more younger people who were economically active. CONCLUSION: Two-thirds of participants endorsed modest-to-high HIV-related stigma, suggesting the prevalence of HIV-related stigma was high among the general population in Hong Kong. Tailored interventions targeting specific stigma drivers and manifestations of individuals as reflected from the stigma profiles of distinct subgroups could form an important strategy for stigma reduction.

Population Behavior Changes Underlying Phasic Shifts of SARS-CoV-2 Exposure Settings Across 3 Omicron Epidemic Waves in Hong Kong: Prospective Cohort Study.

BACKGROUND: Exposure risk was shown to have affected individual susceptibility and the epidemic spread of COVID-19. The dynamics of risk by and across exposure settings alongside the variations following the implementation of social distancing interventions are understudied. OBJECTIVE: This study aims to examine the population's trajectory of exposure risk in different settings and its association with SARS-CoV-2 infection across 3 consecutive Omicron epidemic waves in Hong Kong. METHODS: From March to June 2022, invitation letters were posted to 41,132 randomly selected residential addresses for the recruitment of households into a prospective population cohort. Through web-based monthly surveys coupled with email reminders, a representative from each enrolled household self-reported incidents of SARS-CoV-2 infections, COVID-19 vaccination uptake, their activity pattern in the workplace, and daily and social settings in the preceding month. As a proxy of their exposure risk, the reported activity trend in each setting was differentiated into trajectories based on latent class growth analyses. The associations of different trajectories of SARS-CoV-2 infection overall and by Omicron wave (wave 1: February-April; wave 2: May-September; wave 3: October-December) in 2022 were evaluated by using Cox proportional hazards models and Kaplan-Meier analysis. RESULTS: In total, 33,501 monthly responses in the observation period of February-December 2022 were collected from 5321 individuals, with 41.7% (2221/5321) being male and a median age of 46 (IQR 34-57) years. Against an expanding COVID-19 vaccination coverage from 81.9% to 95.9% for 2 doses and 20% to 77.7% for 3 doses, the cumulative incidence of SARS-CoV-2 infection escalated from <0.2% to 25.3%, 32.4%, and 43.8% by the end of waves 1, 2, and 3, respectively. Throughout February-December 2022, 52.2% (647/1240) of participants had worked regularly on-site, 28.7% (356/1240) worked remotely, and 19.1% (237/1240) showed an assorted pattern. For daily and social settings, 4 and 5 trajectories were identified, respectively, with 11.5% (142/1240) and 14.6% (181/1240) of the participants gauged to have a high exposure risk. Compared to remote working, working regularly on-site (adjusted hazard ratio [aHR] 1.47, 95% CI 1.19-1.80) and living in a larger household (aHR 1.12, 95% CI 1.06-1.18) were associated with a higher risk of SARS-CoV-2 infection in wave 1. Those from the highest daily exposure risk trajectory (aHR 1.46, 95% CI 1.07-2.00) and the second highest social exposure risk trajectory (aHR 1.52, 95% CI 1.18-1.97) were also at an increased risk of infection in waves 2 and 3, respectively, relative to the lowest risk trajectory. CONCLUSIONS: In an infection-naive population, SARS-CoV-2 transmission was predominantly initiated at the workplace, accelerated in the household, and perpetuated in the daily and social environments, as stringent restrictions were scaled down. These patterns highlight the phasic shift of exposure settings, which is important for informing the effective calibration of targeted social distancing measures as an alternative to lockdown.

Is the new tuberculous antigen-based skin test ready for use as an alternative to tuberculin skin test/interferon-gamma release assay for tuberculous diagnosis? A narrative review.

In recent years, novel specific Mycobacteria tuberculous (TB) antigen-based skin test (TBST) has become available for clinical use. The mechanism of TBST is similar to the interferon-gamma release assay (IGRA), making it a potential alternative for identifying latent tuberculous infection (LTBI), especially in subjects with history of bacille Calmette-Guérin vaccination. Three different commercial brands have been developed in Denmark, Russia, and China. Clinical studies in the respective countries have shown promising sensitivity, specificity, and safety profile. Some studies attempted to address the applicability of TBST in specific subject groups but the discrepancy in defining LTBI and problematic methodologies undermine the generalisation of the results to other communities across the world. Limited cost-effectiveness studies for TBST have been conducted without exploring the health economics for preventing development of LTBI into active TB. Unlike IGRA, no clinical studies have addressed the correlation of TBST results (magnitude of induration) with the likelihood of development of active TB. Moreover, the different TBSTs are not widely available for clinical use. While TBST is a promising test to overcome the shortcomings of tuberculin skin tests, more clinical data are needed to support its general application globally for the diagnosis of LTBI.

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.

Mpox vaccination for men who have sex with men and their differential risk of exposure and infection.

Following the post-COVID-19 reopening of the society with enhanced traveling between countries, people at risk of mpox infection, notably men who have sex with men (MSM) and people living with HIV, are facing increasing threat of virus exposure. Mpox vaccination is an important public health strategy which is provided free in Hong Kong to people at higher risk of infection. Between October 2022 and January 2023, 326 and 184 MSM vaccinees from vaccination sites and HIV specialist clinics in Hong Kong, respectively, were recruited for assessing their infection risks. Apart from the urge to protect one's significant others (68%), 45% were worried about the stigmatizing mpox symptoms if infected. Compared with MSM vaccinees at vaccination site, a lower proportion of MSM vaccinees in HIV care were sexually active in the past 6 months (88% vs 97%), but a higher proportion had recent sexually transmitted infection diagnoses (19% vs 10%) and perceived considerable exposure risk in the following 6 months (40% vs 22%). There were no differences in the perceived effectiveness of mpox vaccination. If optimal supplies of mpox vaccines can be secured, a low threshold approach at vaccination site could enable MSM with different levels of behavioral risks to become protected.

Coinfection and repeat bacterial sexually transmitted infections (STI) - retrospective study on male attendees of public STI clinics in an Asia Pacific city.

Without protective immunity, recurrent sexually transmitted infections (STI) could occur. In this study, we retrospectively collected STI diagnosis records from public STI clinics attended by an average of 6,000 male patients annually in Hong Kong in 2009-2019. We estimated the prevalence of three bacterial STI (syphilis, chlamydia and gonorrhoea) coinfection from 2009 to 2019, and examined the factors associated with coinfection in 2014/15 and repeat infection in 2009-2019. We observed an increasing coinfection prevalence in male attendees with bacterial STI over the years, which reached the highest level of 15% in 2019. Among 3,698 male patients in 2014-2015, chlamydia/gonorrhoea coinfection was the commonest among all coinfections (77%). Factors such as young age (29 or below), HIV-positive status, and a history of concurrent genital warts/herpes were positively associated with coinfection in 2014/15 in multivariable logistic regression. Of all male patients with STI coinfection in 2014/15, those of age 30-49 and who self-reported as men who have sex with men (MSM) were more likely to have been repeatedly infected in 2009-2019. The results support the implementation of regular multi-STI testing as an STI control strategy for selected communities like MSM and people living with HIV.

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.

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.