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.

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.

Temporal Changes in Sexually Transmitted Infections in a Cohort of Men Who Have Sex with Men Living with HIV: Sex Partner Seeking and Behavioral Correlates.

With "undetectable equals untransmittable," continued engagement in condomless sex has prolonged STI risk in people living with HIV. This study examined the pattern and relationship between STI diagnosis and sex partner-seeking practice over time in a cohort of men who have sex with men (MSM) attending the HIV specialist clinic in Hong Kong. Participants' STI diagnosis record since HIV diagnosis was retrieved and their frequency of seeking sex partners (A) before, (B) after HIV diagnosis, and (C) following extended period (5-10 years), through eight different settings, was assessed in two rounds of survey, along with their risk behavioral profile. Multivariable regression models were employed to study the factors associated with STI diagnosis and partner-seeking frequency, while their temporal relationships over the three time points (A-C) were examined using cross-lagged panel model. Of 345 subjects recruited, STI incidence dropped from 252 to 187 cases/1000 person-years during 2015-2019. Totally 139/212 MSM (66%) had ≥ 1 episode of STI within the 10-year period after HIV diagnosis, giving an 11-20% annual prevalence. The reduced frequency of seeking sex partner was well preserved following diagnosis with a rebound specifically noted in the use of mobile application, the patrons of which were more likely to be co-infected with STI in 2019. Chemsex, concurrent partnership, and casual sex were risk factors shared between frequent partner-seeking practice and STI diagnosis. A robust autoregressive effect for partner-seeking frequency was also identified, and which significantly predicted STI risk in the long term. To enhance HIV care, the co-administration of STI/behavioral surveillance should be emphasized.

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.