Krystal Chi Kei Lee

Background: Clozapine is widely regarded as a highly efficacious psychotropic drug that is largely underused worldwide. Recent disproportionality analyses and nationwide case-control studies suggested a potential association between clozapine use and hematological malignancy (HM). Nevertheless, the absolute rate difference is not well-established due to the absence of analytic cohort studies. The clinical significance of such a potential risk remains unclear. Methods and findings: We extracted data from a territory-wide public healthcare database from January 2001 to August 2022 in Hong Kong to conduct a retrospective cohort study of anonymized patients aged 18⁺ years with a diagnosis of schizophrenia who used clozapine or olanzapine (drug comparator with highly similar chemical structure and pharmacological mechanisms) for 90⁺ days, with at least 2 prior other antipsychotic use records within both groups. Weighted by inverse probability of treatment (IPTW) based on propensity scores, Poisson regression was used to estimate the incidence rate ratio (IRR) of HM between clozapine and olanzapine users. The absolute rate difference was also estimated. In total, 9,965 patients with a median follow-up period of 6.99 years (25th to 75th percentile: 4.45 to 10.32 years) were included, among which 834 were clozapine users. After IPTW, the demographic and clinical characteristics of clozapine users were comparable to those of olanzapine users. Clozapine users had a significant weighted IRR of 2.22 (95% confidence interval (CI) [1.52, 3.34]; p < 0.001) for HM compared to olanzapine users. The absolute rate difference was estimated at 57.40 (95% CI [33.24, 81.55]) per 100,000 person-years. Findings were consistent across subgroups by age and sex. Sensitivity analyses all supported the robustness of the results and showed good specificity to HM but no other cancers. The main limitation of this observational study is the potential residual confounding effects that could have arisen from the lack of randomization in clozapine or olanzapine use. Conclusions: Absolute rate difference in HM incidence associated with clozapine is small despite a 2-fold elevated rate. Given the rarity of HM and existing blood monitoring requirements, more restrictive indication for clozapine or special warnings may not be necessary.

Background: There is growing concern regarding teratogenic effect of antipsychotics. Previous research assessing association between antipsychotics and congenital malformations (CMs) yielded mixed results and were all derived from Western countries. We aimed to examine risk of major and organ/system-specific CMs associated with prenatal antipsychotic exposure in Hong Kong. Methods: This population-based study identified women aged 15–50 years who delivered their first/singleton child between 2003–2018 from public healthcare service database. Propensity score (PS)-weighted logistic-regression analyses were performed to examine risk of CMs following first-trimester exposure to antipsychotic classes (second- and first-generation antipsychotic; SGA and FGA) and six most frequently-prescribed individual antipsychotics. Results: Of 465,069 women, 419 and 420 redeemed ≥1 prescription of SGA and FGA during first-trimester, respectively. Prevalence of any CMs was 4.9% (95%CI:4.9–5.0%) in unexposed-infants, 9.1% (6.7–12.3%) in SGA-exposed infants, and 6.2% (4.3–9.0%) in FGA-exposed infants. SGA exposure (adjusted-odds-ratio: 2.11 [95%CI:1.19–3.86]) was associated with increased risk of CMs. This finding was consistent with sensitivity analyses addressing exposure misclassification and confounding by treatment indication, but not with PS-matched sensitivity analysis. Elevated risk of CMs was observed in infants exposed to high-dose olanzapine (7.50 [1.65–36.13]) and high-dose quetiapine (15.03 [4.86–56.72]), but with wide-CIs. Organ/system-specific malformations were not associated with SGA, FGA or individual antipsychotics. Conclusion: We observed a small increased risk of major malformations associated with SGA, but was not consistently affirmed in sensitivity analyses, precluding firm conclusions. Research with large sample size clarifying comparative safety of individual antipsychotics on specific malformations is warranted.

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.

Background: Psychotropic substance use, for chemsex in particular, is common in gay or bisexual men (GBM) with HIV infection. This case-control study examined the association between Axis I psychiatric disorders and active psychotropic substance use, and identified factors affecting the prevalence of psychiatric disorders in HIV-infected GBM. Methods: Participants were 62 HIV-infected self-identified GBM who reported psychotropic substance use in the past 1 year (cases), and 55 HIV-infected self-identified GBM without psychotropic substance use in the past 1 year and had negative toxicology tests at recruitment (controls). The Chinese-bilingual Structured Clinical Interview for DSM-IV (Axis I, Patient version) was followed to establish the psychiatric diagnoses. Socio-demographic data, level of social support, HIV-related data, and pattern of psychotropic substance use were collected. Results: Cases had lower level of social support, more depressive disorders (AOR 3.4, 95% CI 1.3-8.7, p=0.01) and psychotic disorders (AOR 7.2, 95% CI 1.2-41, p=0.03) but not anxiety disorders. Significant difference in the prevalence of psychiatric disorders was only evident for disorders with onset after HIV diagnosis. Methamphetamine dependence, weekly methamphetamine use for 2 years or more, using methamphetamine beyond chemsex, duration of HIV diagnosis were significant predictors for psychiatric disorders in the cases. Conclusion: Active psychotropic substance use in HIV-infected gay or bisexual men was associated with an overall 3-fold increase in Axis I psychiatric disorders. Coordinated efforts from HIV, psychiatric and substance use services are needed to prevent harms arising from chemsex and to identify those in need and facilitate treatment access.

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.

Background: Psychotropic substance use is common in HIV-infected gay or bisexual men (GBM). This study examined the association between Axis I psychiatric disorders and active psychotropic substance use, and identified factors affecting the prevalence of psychiatric disorders in HIV-infected GBM.Methods: This is a cross-sectional case-control study taken place in an HIV clinic and community organisations serving people living with HIV or GBM in Hong Kong. Participants were 62 HIV-infected self-identified GBM who reported psychotropic substance use in the past 1 year (cases), and 55 HIV-infected self-identified GBM without psychotropic substance use in the past 1 year and had negative toxicology tests at recruitment (controls).The Chinese-bilingual Structured Clinical Interview for DSM-IV (Axis I, Patient version) was followed to establish the psychiatric diagnoses. Socio-demographic data, level of social support, HIV-related data, and pattern of psychotropic substance use were collected. Results: Cases had lower level of social support (p=0.02), more depressive disorders (AOR 3.4, 95% CI 1.3-8.7, p=0.01) and psychotic disorders (AOR 7.2, 95% CI 1.2-41, p=0.03) but not anxiety disorders. Significant difference in the prevalence of psychiatric disorders was only evident for disorders with onset after HIV diagnosis. Methamphetamine dependence (AOR 6.63, 95% CI 1.53-228.72, pp=0.03), using methamphetamine beyond chemsex (AOR 4.76, 95% CI 1.17-19.41, p=0.03) were significant predictors for psychiatric disorders in the cases in separate logistic regression models. Duration of HIV diagnosis was a significant independent predictor in all three models. Conclusions: Active psychotropic substance use in HIV-infected gay or bisexual men was associated with a 3-fold increase in Axis I psychiatric disorders. This increase in psychiatric disorders was predicted by the severity, duration and context of methamphetamine use and the duration of HIV diagnosis.