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.

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.

Enhanced Cross-Reactive and Polyfunctional Effector-Memory T Cell Responses by ICVAX-a Human PD1-Based Bivalent HIV-1 Gag-p41 Mosaic DNA Vaccine.

Vaccine-induced protective T cell immunity is necessary for HIV-1 functional cure. We previously reported that rhesus PD1-Gag-based DNA vaccination sustained simian-human immunodeficiency virus (SHIV) suppression by inducing effector-memory CD8+ T cells. Here, we investigated a human PD1-Gag-based DNA vaccine, namely, ICVAX, for clinical translation. PD1-based dendritic cell targeting and mosaic antigenic designs were combined to generate the ICVAX by fusing the human soluble PD1 domain with a bivalent HIV-1 Gag-p41 mosaic antigen. The mosaic antigen was cross-reactive with patients infected with B, CRF07/08_BC, and CRF01_AE variants. In mice, ICVAX elicited stronger, broader, and more polyfunctional T cell responses than mosaic Gag-p41 alone, and suppressed EcoHIV infection more efficiently. In macaques, ICVAX elicited polyfunctional effector-memory T cell responses that targeted multiple nonoverlapping epitopes of the Gag-p41 antigen. Furthermore, ICVAX manufactured following good manufacturing practices proved potent immunogenicity in macaques after biannual homologous vaccination, warranting clinical evaluation of ICVAX as an immunotherapy against HIV-1. IMPORTANCE This study presents that ICVAX, a PD1-based DNA vaccine against HIV-1, could induce broad and polyfunctional T cell responses against different HIV-1 subtypes. ICVAX encodes a recombinant antigen consisting of the human soluble PD1 domain fused with two mosaic Gag-p41 antigens. The mosaic antigens cover more than 500 HIV-1 strains circulating in China including the subtypes B/B', CRF01_AE, and CRF07/08_BC. In mice, ICVAX elicited stronger, broader, and more polyfunctional T cell responses, with better EcoHIV suppression than the nontargeting mosaic Gag-p41 DNA vaccine. Moreover, both lab-generated and GMP-grade ICVAX also elicited strong polyfunctional effector-memory T cell responses in rhesus macaques with good immunogenicity against multiple nonoverlapping epitopes of the Gag-p41 antigen. This study therefore highlights the great potential to translate the PD1-based DNA vaccine approach into clinical use, and opens up new avenues for alternative HIV-1 vaccine design for HIV-1 preventive and functional cure.

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.

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.

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.

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.

Distribution of molecular strains of Mycobacterium tuberculosis in an intermediate burden Asia Pacific city.

Hong Kong is an intermediate tuberculosis (TB) burden city in Asia Pacific with slow decline of case notification in the last decade. By 24-loci mycobacterial interspersed repetitive units - variable number of tandem repeats genotyping, we examined 534 Mycobacterium tuberculosis isolates collected from culture-positive hospitalised TB patients in a 1.7 million population geographic region in the city. Overall, 286 (75%) were classified as Beijing genotype, of which 216 (76%) and 59 (21%) belonged to modern and ancient sub-lineage, respectively. Only two cases were genetically clustered while spatial clustering was absent. Male gender, permanent residency in Hong Kong and born in Hong Kong or Mainland China were associated with Beijing genotype. The high prevalence of Beijing modern lineage was similar to that in East Asia, which reflected the pattern resulting from population migration. The paucity of clustering suggested that reactivation accounted for most of the TB disease cases, which was and echoed by observation that half were 60 years old or above, and the presence of co-morbid medical conditions. The predominance of reactivation TB cases in intermediate burden localities implies that the detection and control of latent TB infection would be the major challenge in achieving TB elimination.

Complexation of clofazimine by macrocyclic cucurbit[7]uril reduced its cardiotoxicity without affecting the antimycobacterial efficacy.

Cucurbit[7]uril (CB[7]) has recently attracted increasing attention in pharmaceutical sciences due to its great potential in improving the physicochemical properties and bioactivity of drug molecules. Herein, we have investigated the influence of CB[7]'s complexation on the solubility, antimycobacterial activity, and cardiotoxicity of a model anti-tuberculosis drug, clofazimine (CFZ), that has poor water-solubility and inherent cardiotoxicity. In our study, CFZ was found to be complexed by CB[7], in a 1 : 1 binding mode with a relatively strong binding affinity (in the order of magnitude of 10(4)-10(5) M(-1)), as determined by the phase solubility method via HPLC-UV analysis and (1)H NMR titration, as well as UV-visible spectroscopic titration, and further confirmed by electrospray ionization mass spectrometry (ESI-MS). Upon complexation, the solubility of virtually insoluble CFZ was significantly increased, reaching a concentration of up to approximately 0.53-fold of the maximum solubility of CB[7]. The inherent cardiotoxicity of CFZ was dramatically reduced to almost nil in the presence of CB[7]. Importantly, on the other hand, such a supramolecular complexation of the drug did not compromise its therapeutic efficacy, as shown by the antimycobacterial activities examined against Mycobacterium smegmatis, demonstrating the significant potential of CB[7] as a functional pharmaceutical excipient.

Failure of self-disclosure of deferrable risk behaviors associated with transfusion-transmissible infections in blood donors.

BACKGROUND: To date, most studies on deferral of blood donors have focused on men who have sex with men (MSM) and/or injecting drug users. Few have examined deferrable risk behaviors relating to transfusion-transmissible infections (TTIs) in general. This study aimed to examine the prevalence of, and factors associated with, nondisclosure of TTI-related risk behaviors in donors. STUDY DESIGN AND METHODS: Chinese-speaking donors who had just given blood in Hong Kong were invited to self-complete an anonymous questionnaire. Practices of one or more of seven deferrable risk behaviors associated with TTI were inquired. Factors associated with noncompliance with self-disclosure were evaluated by logistic regression. RESULTS: Over a 4-week study period in 2012, a total of 1143 donors were recruited. Overall, 0.2% gave a history of drug injection, 1.7% had had sex with sex worker(s), and 0.3% had had sex with a human immunodeficiency virus-infected partner, while none had been paid for sex. Some 1.5% of male donors reported having same-sex behaviors. Factors associated with noncompliance were male gender (odds ratio [OR] 31.1; 95% confidence interval [CI], 3.7-263.6), having multiple sex partners (OR, 89.7; 95% CI, 28.7-279.9), and previous history of temporary deferral (OR, 11.4; 95% CI, 2.5-53.3). If suspected noncompliance was included, the overall prevalence of nondisclosure of deferrable behaviors could be high at 6.5%. CONCLUSION: Albeit uncommon, some donors fail to provide accurate answers to predonation screening questions and are not deferred appropriately. There is room for improvement to make deferral policy acceptable and understandable, so as to minimize the risk of TTI. Efforts are also needed to tackle the paucity of data on noncompliance of non-MSM donors.

Usage and acceptability of HIV self-testing in men who have sex with men in Hong Kong.

Whilst studies on over-the-counter HIV tests continue to accumulate after FDA's approval of OraQuick Advance in 2012, few have focused on men who have sex with men (MSM) in Asian cities. An internet survey was conducted on 1,122 MSM in Hong Kong, revealing a low usage (6.1 %) and acceptability rate (43.8 %) on self-testing despite its availability in the market. Hierarchical logistic regression models showed that having received relevant information and users' attitudes on self-testing were the determinants of usage and acceptability. These factors had greater effects than sexual behaviors and social-networking on MSM's decision on self-testing. Majority of ever self-testers only repeated the self-test after a non-negative result, and overall only 26.6 % went for a formal test subsequent to the self-test. Concerns regarding the tests' accuracy were expressed by respondents. In conclusion, appropriate and accessible information and evidence-based guidance are needed to incorporate self-testing into HIV prevention strategies targeting MSM.

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.

Emergence of antibiotic-resistant Mycoplasma genitalium as the cause of non-gonococcal urethritis in male patients at a sexually transmitted infection clinic.

Mycoplasma genitalium is the cause of an emerging sexually transmitted infection (STI) with high propensity for development of antimicrobial resistance. In a prevalence study conducted at the public STI service in Hong Kong, the first void urine samples of 38 (8%) of 493 male patients with non-gonococcal urethritis (NGU) tested positive for M. genitalium using reverse transcription polymerase chain reaction. Patients with M. genitalium infection were younger [31 vs 33 years, odds ratio (OR) 0.96, 95% confidence interval (CI) 0.93-0.996; P=0.03], more likely to present with urethral discharge (12% vs 6%, OR 2.16, 95% CI 1.10-4.23; P=0.02) and had symptom duration >2 weeks (14% vs 6%, OR 2.34, 95% CI 1.10-4.97; P=0.03) compared with patients without M. genitalium infection. The prevalence of M. genitalium infection was lower in patients co-infected with Chlamydia trachomatis compared with patients with isolated infection (4% vs 10%, OR 0.38, 95% CI 0.17-0.84; P=0.02). The prevalence of M. genitalium infection was not higher in men who have sex with men. Antimicrobial-resistance-conferring mutations were present in 24 (63%) patients with M. genitalium - 23S rRNA 18 (47%) and parC 19 (53%). Similar to neighbouring countries in the Asia Pacific region, concurrent resistance mutations against both macrolides and fluoroquinolones were demonstrated in 14 (37%) patients. Histories of azithromycin and moxifloxacin use were significantly associated with a diagnosis of M. genitalium infection. Characteristically, NGU in Hong Kong featured the co-existence of mono-resistance against macrolides or fluoroquinolones, and the presence of dual class resistance. The geographic variability of antimicrobial resistance against M. genitalium is attributed not just to the different transmission networks formed in separate population groups, but the antimicrobial prescriptions for the treatment of urethritis in the community.

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.

Comparison between daily and on-demand PrEP (pre-exposure prophylaxis) regimen in covering condomless anal intercourse for men who have sex with men in Hong Kong: A randomized, controlled, open-label, crossover trial.

INTRODUCTION: Both daily and on-demand regimens have been proven effective for pre-exposure prophylaxis (PrEP) against HIV in men who have sex with men (MSM). We aimed to compare the two regimens on their coverage of condomless anal intercourse (CLAI) in MSM. METHODS: A randomized, controlled, open-label, crossover trial was conducted in a teaching hospital in Hong Kong. Participants were sexually active HIV-negative MSM aged 18 years or above with normal renal function and without chronic hepatitis B infection. Oral tenofovir disoproxil fumarate 300 mg/emtricitabine 200 mg (TDF/FTC) tablets were prescribed for PrEP. After a 2-week lead-in with daily TDF/FTC for treatment-naïve MSM for tolerance assessment, participants were randomly assigned in a 1:1 ratio with a block size of four to either daily-first or on-demand-first arm based on the IPERGAY study, for receiving PrEP for 16 weeks, then crossed-over to the alternative regimen for another 16 weeks. The primary outcome was the proportion of days with PrEP-covered CLAI by intention-to-treat analysis. The trial is registered with the CCRB Clinical Trials Registry, CUHK, CUHK_CCRB00606, and is closed to accrual. RESULTS: Between 25 August 2018 and 23 March 2019, 119 eligible participants were assigned to daily-first arm (n = 59) and on-demand-first arm (n = 60) with an 87% overall completion rate (n = 103). With 96% and 54% of days on PrEP during daily and on-demand periods, respectively, the proportion of days with PrEP-covered CLAI between two arms were not statistically different (92% vs. 92%, p = 0.93). About half (47%) were diagnosed with at least one episode of incident sexually transmitted infection. Mild and time-limited adverse events, including diarrhoea, headache, nausea and dizziness, were reported in 37 (31%) and 10 (8%) during the daily and on-demand periods, respectively. At the end of the study, a similar proportion favoured daily or on-demand regimen. CONCLUSIONS: High prevention-effective adherence, as reflected from the coverage of CLAI, was achievable by either daily or on-demand PrEP among MSM, albeit a higher number of tablets taken for daily PrEP. As both regimens were well accepted, a flexible approach adopting either or both regimens with possible switching is warranted in order to suit individual health needs.

Review on the molecular epidemiology of sexually acquired hepatitis C virus infection in the Asia-Pacific region.

INTRODUCTION: Sexual acquisition has emerged as a transmission route for hepatitis C virus (HCV) of growing importance among human immunodeficiency virus (HIV)-positive populations. In Western countries, HCV epidemics have been increasingly detected among men who have sex with men (MSM). This review describes the molecular epidemiology of sexually acquired HCV infection in the Asia-Pacific region. METHODS: A systematic search was performed on PubMed in March 2019. Either abstract or full-text of each publication in the search results was screened for eligibility. Studies from different countries/cities involving eligible cases, who acquired HCV sexually with identified subtype, were synthesized for the evaluation of molecular epidemiology in the Asia-Pacific region. Two large-scale systematic reviews on the genotype distribution of HCV at a population level and among PWID were used as references for comparison. RESULTS AND DISCUSSION: Overall, 13 full-text articles with 549 subjects originating from nine countries/cities were reviewed. A total of five genotypes and 14 subtypes were identified, dominated by subtypes 1b (23.0%), 2a (19.1%) and 3a (29.5%). A majority of the infected cases occurred in HIV-positive MSM. In some places, notably Hong Kong, India and Indonesia, the predominant subtype in sexually acquired HCV infection in MSM was different from that circulating in the general population. Shared transmission networks between people who inject drugs (PWID) and MSM were shown in Australia and New Zealand, whereas overlapping risk elicited from a small number of subjects existed in Tokyo, Taipei and Guangxi. MSM-specific clusters were identified in Hong Kong, Taipei and Hubei. CONCLUSIONS: The distribution of sexually acquired HCV was sparsely scattered across countries/cities in the Asia-Pacific region. The threat of overlapping risk differed by locations, whereas transnational outbreaks remained uncommon. The paucity of information has hindered progress with comprehensive assessment in the Asia-Pacific region, where seroprevalence of HCV among HIV-positive MSM was relatively high.

Incorporation of information diffusion model for enhancing analyses in HIV molecular surveillance.

Molecular surveillance of infections is essential in monitoring their transmission in the population. In this study, newly diagnosed HIV patients' phylogenetic, clinical and behavioural data were integrated, and an information diffusion model was incorporated in analysing transmission dynamics. A genetic network was constructed from HIV sequences, from which transmission cascades were extracted. From the transmission cascades, CRF01_AE had higher values of information diffusion metrics, including scale, speed and range, than that of B, signifying the distinct transmission patterns of two circulating subtypes in Hong Kong. Patients connected in the network, were more likely male, younger, of main circulating subtypes, to have acquired HIV infection locally, and a higher CD4 level at diagnosis. Genetic connections varied among men who have sex with men (MSM) who used different channels of sex networking and varied in their engagement in risk behaviours. MSM using recreational drugs for sex held positions of greater importance within the network. Significant differences in network metrics were observed among MSM as differentiated by their mobile apps usage patterns, evidencing the impact of social network on transmission networks. The applied model in the presence of consistently collected longitudinal data could enhance HIV molecular epidemiologic surveillance for informing future intervention planning.