History of Rectal Product Use and Country of Residence Influence Preference for Rectal Microbicide Dosage Forms Among Young Sexual and Gender Minorities: A Multi-country Trial Comparing Placebo Douche, Suppository, and Insert Products.

The DESIRE Study (MTN-035) explored product preference among three placebo rectal microbicide (RM) formulations, a rectal douche (RD), a suppository, and an insert, among 210 sexually active transgender people and men who have sex with men in five counties: the United States, Peru, Thailand, South Africa, and Malawi. Participants used each product prior to receptive anal sex (RAS) for 1 month, following a randomly assigned sequence, then selected their preferred product via computer assisted self-interview. In-depth interviews examined reasons for preference. We compared product preference and prior product use by country to explore whether geographic location and experience with the similar products impacted preference. A majority in the United States (56%) and Peru (58%) and nearly half in South Africa (48%) preferred the douche. Most in Malawi (59%) preferred the suppository, while half in Thailand (50%) and nearly half in South Africa (47%) preferred the insert. Participants who preferred the douche described it as quick and easy, already routinized, and serving a dual purpose of cleansing and protecting. Those who preferred the insert found it small, portable, discreet, with quick dissolution. Those who preferred the suppository found the size and shape acceptable and liked the added lubrication it provided. Experience with product use varied by country. Participants with RD experience were significantly more likely to prefer the douche (p = 0.03). Diversifying availability of multiple RM dosage forms can increase uptake and improve HIV prevention efforts globally.

RESUMEN: El estudio DESIRE (MTN-035) exploró la preferencia de producto entre tres formulaciones de microbicida rectal (MR) de placebo, una ducha rectal, un supositorio y un inserto, entre 210 personas transgénero y hombres que tienen sexo con hombres en cinco países: los Estados Unidos, Perú., Tailandia, Sudáfrica y Malawi. Los participantes utilizaron cada producto antes del sexo anal receptive (SAR) durante un mes, siguiendo una secuencia asignada al azar, luego seleccionaron su producto preferido mediante una autoentrevista asistida por computadora. Las entrevistas en profundidad examinaron los motivos de preferencia. Comparamos la preferencia de producto y el uso previo del producto por país para explorar si la ubicación geográfica y la experiencia con la forma farmacéutica impactaron la preferencia. Una mayoría en los Estados Unidos (56%) y Perú (58%) y casi la mitad en Sudáfrica (48%) prefirieron la ducha rectal. La mayoría en Malawi (59%) prefirió el supositorio, mientras que la mitad en Tailandia (50%) y casi la mitad en Sudáfrica (47%) prefirió el inserto. Los participantes que prefirieron la ducha rectal la describieron como rápida y fácil, ya parte de su rutina y que tenía el doble propósito de limpiar y proteger. Los que prefirieron el inserto lo consideraron pequeño, portátil, discreto y de rápida disolución. Los que prefirieron el supositorio encontraron que tenía un tamaño y forma aceptables y proveía lubricación adicional. La experiencia con el uso del producto varió según el país. Los participantes con experiencia con duchas rectales tenían significativamente más probabilidades de preferir la ducha rectal (p = 0,03). Diversificar la disponibilidad de múltiples formas farmacéuticas de MR puede aumentar la aceptación y mejorar los esfuerzos de prevención del VIH a nivel mundial.

A conjoint experiment of three placebo rectal products used with receptive anal sex: results from MTN-035.

INTRODUCTION: End-user perspectives are vital to the design of new biomedical HIV prevention products. Conjoint analysis can support the integration of end-user perspectives by examining their preferences of potential pre-exposure prophylaxis (PrEP) products. The Microbicides Trial Network (MTN) 035 protocol examined three placebo rectal dosage forms (insert, enema and suppository) that could deliver PrEP prior to receptive anal sex (RAS). METHODS: Between April 2019 and July 2020, we enrolled 217 HIV-negative, cisgender men who have sex with men (MSM; n = 172; 79.3%) and transgender people (n = 47; 20.7%) ages 18-35 into a randomized cross-over trial across Malawi, Peru, South Africa, Thailand and the United States. Participants used each product prior to RAS over 4-week periods. Participants completed a conjoint experiment where they selected between random profiles using seven features (dosage form, timing of use before sex, side effects, duration of protection, effectiveness, frequency of use and need for a prescription). RESULTS: Effectiveness was the strongest determinant of choice (30.4%), followed by modality (18.0%), potential side effects (17.2%), frequency of use (10.8%), duration of protection (10.4%), timing of use before sex (7.4%) and need for a prescription (5.9%). Relative utility scores indicated that the most desirable combination of attributes was a product with 95% efficacy, used 30 minutes before sex, offering a 3- to 5-day protection window, used weekly, having no side effects, in the form of an enema and available over-the-counter. CONCLUSIONS: Choice in next-generation PrEP products is highly desired by MSM and transgender people, as no one-size-fits-all approach satisfies all the preferences. MTN-035 participants weighed product features differently, recognizing the need for diverse, behaviourally congruent biomedical options that fit the needs of intended end-users.

Innate immune cell activation after HIV-1 vaccine administration is associated with increased antibody production.

The RV144 Thai phase III clinical trial's canarypox-protein HIV vaccine regimen showed modest efficacy in reducing infection. We therefore sought to determine the effects of vaccine administration on innate cell activation and subsequent associations with vaccine-induced immune responses. RV306 was a randomized, double-blind clinical trial in HIV-uninfected Thai adults that tested delayed boosting following the RV144 regimen. PBMC collected from RV306 participants prior to and 3 days after the last boost were used to investigate innate immune cell activation. Our analysis showed an increase in CD38+ mucosal associated invariant T (MAIT) cells, CD38+ invariant natural killer T (iNKT) cells, CD38+ γδ T cells, CD38+, CD69+ and HLA-DR+ NK cells 3 days after vaccine administration. An increase in CD14-CD16+ non-classical monocytes and CD14+CD16+ intermediate monocytes accompanied by a decrease in CD14+CD16- classical monocytes was also associated with vaccine administration. Inclusion of ALVAC-HIV in the boost did not further increase MAIT, iNKT, γδ T, and NK cell activation or increase the proportion of non-classical monocytes. Additionally, NK cell activation 3 days after vaccination was positively associated with antibody titers of HIV Env-specific total IgG and IgG1. Vδ1 T cell activation 3 days after vaccine administration was associated with HIV Env-specific IgG3 titers. Finally, we observed trending associations between MAIT cell activation and Env-specific IgG3 titers and between NK cell activation and TH023 pseudovirus neutralization titers. Our study identifies a potential role for innate cells, specifically NK, MAIT, and γδ T cells, in promoting antibody responses following HIV-1 vaccine administration.

A latent trajectory analysis of young sexual and gender minorities' adherence to three rectal microbicide placebo formulations (MTN-035; a randomized crossover trial).

BACKGROUND: Rectal microbicides (RM) are biomedical HIV prevention products that aim to prevent or reduce the transmission of HIV and other sexually transmitted infections (STIs). RM modalities may be beneficial for populations who have complex lifestyles, difficulties adhering to pre-exposure prophylaxis (PrEP) regimens, and/or have limited access to care. MTN-035 (DESIRE; Developing and Evaluating Short-Acting Innovations for Rectal Use), a randomized crossover trial, aimed to evaluate the safety and acceptability of, and adherence to, three placebo RM modalities (douche, insert, and suppository) prior to receptive anal intercourse. METHODS: We conducted latent trajectory analysis to identify clusters of individuals who shared similar trajectories in acceptability and adherence for each product (douche, insert, and suppository) over time. We analyzed weekly short messaging service (SMS) use reports for each modality as reported by enrolled sexual and gender minority (SGM) participants. RESULTS: Two trajectories for each product were identified: a "protocol compliant" trajectory (i.e., at least one product use occasion per week) and "high use" trajectory (i.e., more than three product use occasions per week). Participants with high use were more likely to lack access to PrEP and have higher intentions to utilize RM modalities compared to those who were protocol compliant. CONCLUSIONS: This study highlighted high adherence to RM modalities among SGM. As research into viable HIV prevention modalities continues to evolve, tailored intervention strategies are needed to support the uptake of and adherence to alternative prevention modalities that are behaviorally congruent with targeted users. TRIAL REGISTRATION: NCT03671239 (14/09/2018).

Role of booster vaccines and hybrid immunity against severe COVID-19 outcomes during BA.5 omicron predominance in Thailand.

Owing to both vaccine- and infection-induced immunity, the COVID-19 seroprevalence is ~90% in most countries. It is important to examine the protective role of booster vaccines and hybrid immunity in the COVID-endemic state. Utilizing a hospital information system for COVID-19, we conducted a cohort study by linking laboratory-confirmed COVID-19 case data to the national immunization records during the BA.5 omicron predominant period (1 August-31 December 2022) in Chiang Mai, Thailand. Out of 63,009 adults with COVID-19 included in the study, there were 125 (0.2%) severe COVID outcomes and 6.4% had a previous omicron infection. Protection against severe COVID-19 was highest among those with at least one booster vaccine (63%; aHR 0.37 [95%CI 0.19-0.73]) as compared to those without prior vaccination or natural infection. Hybrid immunity offered better protection (35%; aHR 0.65 [95%CI 0.09-4.73) than primary vaccine series alone or previous infection alone. Evaluating risk by age group, those aged 70 years or more had nearly 40 times (aHR 39.58 [95%CI 18.92-82.79]) the risk of severe-COVID-19 as compared to the 18-39-year age group. While booster vaccines remain the most effective way of protecting against severe COVID-19, particularly in the elderly, hybrid immunity may offer additional benefit.

Heterologous booster vaccines reduce severity and mortality in COVID-19 during BA.2 and BA.4/BA.5 omicron predominance in Thailand.

BACKGROUND: The COVID-19 pandemic has evolved quickly, with variants of concern resulting in the need to offer booster vaccinations. Unfortunately, the booster uptake has been slow and vaccine response has shown to wane over time. Therefore, it's critical to evaluate the role of vaccinations on outcomes with newer sub-lineages of omicron. METHODS: Utilising a Hospital Information System established in Chiang Mai, Thailand, we conducted a cohort study by linking patient-level data of laboratory-confirmed COVID-19 cases to the national immunization records, during BA.2 and BA.4/BA.5 predominance. RESULTS: In adjusted cox-proportional hazard models, BA.4/BA.5 was not associated with more severe COVID-19 outcomes or deaths as compared to BA.2. Risk of severe outcomes and deaths were significantly reduced with third (87% and 95%) and fourth (88% and 95%) dose vaccination, while events were not observed with a fifth dose. Across the regimens, vaccination within 14-90 days prior showed the highest level of protection. All the vaccine types used for boosting in Thailand offered similar protection against severe COVID-19. CONCLUSIONS: Boosters provide high level of protection against severe COVID-19 outcomes and deaths with newer omicron sub-lineages. Booster campaigns should focus on improving coverage utilising all available vaccines to ensure optimal protection.

Higher milk consumption is associated with a lower risk of diabetes mellitus: A case-control study.

BACKGROUND & AIMS: Studies have determined that people with genetically defined lactase non-persistence have lower dairy intake that may lead to an increase risk of various non-communicable diseases. Furthermore, lactase non-persistence itself has been associated with insulin resistance. However, data on lactase non-persistence status and dairy intake in developing countries are sparse. We therefore aimed to define 1) the prevalence of lactase non-persistence among individuals with diabetes and non-diabetes in Thai population and 2) the links between lactase non-persistence, milk consumption, and risk of diabetes mellitus. METHODS: We conducted a case-control study from participants of the National Health Examination Survey. DNA was isolated from the blood for LCT -13910C>T (rs4988235) polymorphism and processed using the Bio-rad c1000 touch thermal cycler and MALDI-TOF Mass Spectrometry MassARRAY Typer v4.0 (Agena Bioscience, San Diego, CA, USA) at the Center for Medical Genomics, Faculty of Medicine Ramathibodi Hospital. Cases were participants with previously diagnosed diabetes mellitus or fasting plasma glucose ≥126 mg/dL (n = 1,756) vs. the controls (n = 2,380). RESULTS: We included 4,136 participants, 62% female, and 98.8% were > 30 years old. Homozygous CC genotype (i.e., lactase non-persistence) was noted in 98.6% and only 1.4% carried heterozygous CT. Most (76%) consumed milk <1 portion/month. Participants with either CC or CT genotype had comparable milk consumption and the risk of diabetes mellitus. Males, older adults, and lower education had a lower chance of consuming milk at least one portion per month. Besides various baseline variables, we found that higher milk consumption was associated with a lower DM risk (P = .01). CONCLUSION: The prevalence of lactase non-persistence in Thai population is very high. A significant difference in milk consumption frequency in relation to the lactase non-persistence status was not found. However, higher milk consumption is associated with a lower risk of diabetes mellitus.

Additional boosting to the RV144 vaccine regimen increased Fc-mediated effector function magnitude but not durability.

OBJECTIVES: The RV144 vaccine trial resulted in a decreased risk of HIV acquisition that was associated with a nonneutralizing antibody response. The objective of this study was to determine the impact of an additional boost to the RV144 vaccine regimen on antibody effector function and durability. DESIGN: RV306 was a randomized, double-blind late boosting of the RV144 prime-boost regimen in HIV-uninfected Thai adults (NCT01931358). This analysis included study participants who received the RV144 vaccine regimen and received no additional boost (group 1) or were boosted with ALVAC-HIV and AIDSVAX (group 2) or only AIDSVAX alone (group 3) 24 weeks after completing the RV144 series. METHODS: Plasma samples from RV306 study participants were used to measure antibody-dependent cellular phagocytosis (ADCP), antibody-dependent neutrophil phagocytosis (ADNP), antibody-dependent complement deposition (ADCD), antibody-dependent cellular cytotoxicity (ADCC), trogocystosis, and gp120-specifc IgG subclasses. RESULTS: Additional boosting increased the magnitude of all Fc-mediated effector functions 2 weeks following the additional boost compared with 2 weeks after completing the RV144 regimen. However, only trogocytosis remained higher 24-26 weeks after the last vaccination for the study participants receiving an additional boost compared with those that did not receive an additional boost. The additional boost increased IgG1 and IgG4 but decreased IgG3 gp-120 specific antibodies compared with 2 weeks after completing the RV144 regimen. CONCLUSION: Additional boosting of RV144 improved the magnitude but not the durability of some Fc-mediated effector functions that were associated with vaccine efficacy, with trogocytosis being the most durable.

ALVAC-HIV and AIDSVAX B/E vaccination induce improved immune responses compared with AIDSVAX B/E vaccination alone.

The RV144 phase III vaccine trial demonstrated that ALVAC-HIV and AIDSVAX B/E administration over 6 months resulted in 31% efficacy in preventing HIV acquisition, while administration of AIDSVAX B/E alone in both VAX003 and VAX004 studies failed to show efficacy. In this study, we aimed to understand the impact of ALVAC-HIV on the development of cellular, humoral, and functional immune responses compared to the administration of AIDSVAX B/E alone. ALVAC-HIV in combination with 3 doses of AIDSVAX B/E significantly increased CD4+ HIV-specific T cell responses, polyfunctionality, and proliferation compared with 3 doses of AIDSVAX B/E alone. Additionally, Env-specific plasmablasts and A244-specific memory B cells were identified with a significantly higher magnitude in the group that received ALVAC-HIV. Subsequently, data revealed increased magnitude of plasma IgG binding to and avidity for HIV Env in participants who received ALVAC-HIV compared with 3 doses of AIDSVAX B/E alone. Lastly, levels of the Fc-mediated effector functions antibody-dependent cellular cytotoxicity, NK cell activation, and trogocytosis were significantly increased in participants who received ALVAC-HIV compared with those receiving AIDSVAX B/E alone. Taken together, these results suggest that ALVAC-HIV plays an essential role in developing cellular and humoral immune responses to protein-boosted regimens relative to protein alone.

Waning vaccine response to severe COVID-19 outcomes during omicron predominance in Thailand.

BACKGROUND: The COVID-19 pandemic has evolved quickly, with different variants of concern resulting in the need to offer continued protection through booster vaccinations. The duration of enhanced protection with booster doses against severe COVID-19 is still unclear. Understanding this is critical to recommendations on the frequency of future booster doses. METHODS: Utilising a Hospital Information System for COVID-19 established in Chiang Mai, Thailand, we conducted a cohort study by linking patient-level data of laboratory-confirmed COVID-19 cases to the national immunization records, during the omicron predominant period (1 February- 31 July 2022). RESULTS: Out of 261,103 adults with COVID-19 included in the study, there were 333 (0.13%) severe COVID-19 cases and 190 (0.07%) deaths. Protection against severe COVID-19 was highest with boosters received >14-60 days prior to positive test (93%) and persisted at >60-120 days (91%) but started to wane at >120-180 days (77%) and further at >180 days (68%). The rate of waning differed with age. Those ≥70 years showed faster waning of booster vaccine responses as compared to those aged 18-49 years, who retained good responses up to 180 days. Equivalent risk reduction against severe COVID-19 was seen with all the vaccine types used as boosters in Thailand. CONCLUSIONS: Booster doses provided high levels of protection against severe COVID-19 with omicron, up to 4 months. Repeat boosters will be required to continue protection beyond 4 months, particularly in the elderly. mRNA and viral vector vaccines can be used flexibly to improve booster coverage.

A randomized trial of safety, acceptability and adherence of three rectal microbicide placebo formulations among young sexual and gender minorities who engage in receptive anal intercourse (MTN-035).

Efforts to develop a range of HIV prevention products that can serve as behaviorally congruent viable alternatives to consistent condom use and oral pre-exposure prophylaxis (PrEP) remain crucial. MTN-035 was a randomized crossover trial seeking to evaluate the safety, acceptability, and adherence to three placebo modalities (insert, suppository, enema) prior to receptive anal intercourse (RAI). If participants had no RAI in a week, they were asked to use their assigned product without sex. We hypothesized that the modalities would be acceptable and safe for use prior to RAI, and that participants would report high adherence given their behavioral congruence with cleansing practices (e.g., douches and/or enemas) and their existing use to deliver medications (e.g., suppositories; fast-dissolving inserts) via the rectum. Participants (N = 217) were sexual and gender minorities enrolled in five different countries (Malawi, Peru, South Africa, Thailand, and the United States of America). Mean age was 24.9 years (range 18-35 years). 204 adverse events were reported by 98 participants (45.2%); 37 (18.1%) were deemed related to the study products. The proportion of participants reporting "high acceptability" was 72% (95%CI: 65% - 78%) for inserts, 66% (95%CI: 59% - 73%) for suppositories, and 73% (95%CI: 66% - 79%) for enemas. The proportion of participants reporting fully adherent per protocol (i.e., at least one use per week) was 75% (95%CI: 69% - 81%) for inserts, 74% (95%CI: 68% - 80%) for suppositories, and 83% (95%CI: 77% - 88%) for enemas. Participants fully adherent per RAI-act was similar among the three products: insert (n = 99; 58.9%), suppository (n = 101; 58.0%) and enema (n = 107; 58.8%). The efficacy and effectiveness of emerging HIV prevention drug depends on safe and acceptable delivery modalities that are easy to use consistently. Our findings demonstrate the safety and acceptability of, and adherence to, enemas, inserts, and suppositories as potential modalities through which to deliver a rectal microbicide.

Extended Analysis of HIV Infection in Cisgender Men and Transgender Women Who Have Sex with Men Receiving Injectable Cabotegravir for HIV Prevention: HPTN 083.

HPTN 083 demonstrated that injectable cabotegravir (CAB) was superior to oral tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) for HIV prevention in cisgender men and transgender women who have sex with men. We previously analyzed 58 infections in the blinded phase of HPTN 083 (16 in the CAB arm and 42 in the TDF-FTC arm). This report describes 52 additional infections that occurred up to 1 year after study unblinding (18 in the CAB arm and 34 in the TDF-FTC arm). Retrospective testing included HIV testing, viral load testing, quantification of study drug concentrations, and drug resistance testing. The new CAB arm infections included 7 with CAB administration within 6 months of the first HIV-positive visit (2 with on-time injections, 3 with ≥1 delayed injection, and 2 who restarted CAB) and 11 with no recent CAB administration. Three cases had integrase strand transfer inhibitor (INSTI) resistance (2 with on-time injections and 1 who restarted CAB). Among 34 CAB infections analyzed to date, diagnosis delays and INSTI resistance were significantly more common in infections with CAB administration within 6 months of the first HIV-positive visit. This report further characterizes HIV infections in persons receiving CAB preexposure prophylaxis and helps define the impact of CAB on the detection of infection and the emergence of INSTI resistance.

Ideal cardiovascular health and all-cause or cardiovascular mortality in a longitudinal study of the Thai National Health Examination Survey IV and V.

The relationship of ideal cardiovascular health (CVH) and health outcomes has been rarely assessed in middle-income countries. We determined the ideal CVH metrics and association with all-cause and cardiovascular (CVD) mortality in the Thai population. We used baseline data from two rounds of the National Health Examination survey (15,219 participants in 2009 and 14,499 in 2014), and assessed all-cause and CVD deaths until 2020. The prevalence of 5-7 ideal CVH metrics in 2009 was 10.4% versus 9.5% in 2014. During a median follow-up of 7.1 years, the all-cause and CVD mortality rates were 19.4 and 4.6 per 1000 person-years for 0-1 ideal CVH metrics, and 13.0 and 2.1, 9.6 and 1.5, 6.0 and 1.0, and 2.9 and 0.4 per 1000 person-years for 2, 3, 4, and 5-7 ideal CVH metrics, respectively. Participants with 2, 3, 4, or 5-7 ideal metrics had a significantly lower risk of mortality than those with 0-1 ideal CVH metrics (adjusted hazard ratios: 0.75, 0.70, 0.60, and 0.47 for all-cause, and 0.54, 0.52, 0.50, and 0.31 for CVD, respectively). Individuals with a higher number of the modified ideal CVH metrics have a lower risk of all-cause and CVD mortality.

Stigmatizing and discriminatory attitudes toward people living with HIV/AIDS (PLWHA) among general adult population: the results from the 6th Thai National Health Examination Survey (NHES VI).

Background: Thailand has an ongoing action plan to reduce human immunodeficiency virus (HIV) discrimination and stigma. We aimed to monitor the level of stigmatizing and discriminatory attitudes toward people living with HIV/AIDS (PLWHA) among the general adult population and to investigate its related factors. Methods: This study was based on data from the 6th Thai National Health Examination Survey, a large-scale country-wide survey in 2019-2020. We used a multistage sampling technique and included 11 843 adults aged 20 to 59. We collected data through face-to-face interviews which included six items related to HIV stigma domains. We weighted all analyses to account for the probability of sampling the Thai population aged 20 to 59 years. Results: We found that anticipated stigma had the highest percentage of negative stigmatizing attitude responses (78.5%), followed by perceived stigma (66.6%), fear of HIV infection (54.4%), and social judgment (28.2%). Regarding the UNAIDS global indicator for discriminatory attitude, 48.6% of respondents had negative perceptions to questions about experienced stigma or discrimination. Multiple logistic regression showed that factors associated with discriminatory attitudes toward PLWHA were being aged 20-39 (adjusted odds ratio (aOR) = 1.32, 95% confidence interval (CI) = 1.18-1.47) or 50-59 (aOR = 1.23, 95% CI = 1.09-1.40) compared to being aged 40-49, being Muslim compared to Buddhist (aOR = 1.73, 95% CI = 1.46-2.06), being married compared to being single (aOR = 1.15, 95% CI = 1.04-1.28), holding certificate degree or higher compared to not studying or studying at a primary level (aOR = 0.81, 95% CI = 0.68-0.97), living in the Northeast (aOR = 1.27, 95% CI = 1.12-1.45) and Bangkok (aOR = 1.30, 95% CI = 1.12-1.51) compared to living in the North, having no HIV/AIDS infected relative or acquaintance compared to having an HIV/AIDS infected relative or acquaintance (aOR = 1.56, 95% CI = 1.41-1.73), and not obtaining an HIV test compared to obtaining it (aOR = 1.10, 95% CI = 1.02-1.19). Conclusions: We found that HIV stigmatizing and discriminatory attitudes toward PLWHA decreased, but remained concerning among Thai adult people. A public education and awareness campaign, as well as an intervention to reduce HIV-related stigma and discrimination in the country's health care facilities, must still be maintained.

Expert review of global real-world data on COVID-19 vaccine booster effectiveness and safety during the omicron-dominant phase of the pandemic.

INTRODUCTION: COVID-19 vaccines have been highly effective in reducing morbidity and mortality during the pandemic. However, the emergence of the Omicron variant and subvariants as the globally dominant strains have raised doubts about the effectiveness of currently available vaccines and prompted debate about potential future vaccination strategies. AREAS COVERED: Using the publicly available IVAC VIEW-hub platform, we reviewed 52 studies on vaccine effectiveness (VE) after booster vaccinations. VE were reported for SARS-CoV-2 symptomatic infection, severe disease and death and stratified by vaccine schedule and age. In addition, a non-systematic literature review of safety was performed to identify single or multi-country studies investigating adverse event rates for at least two of the currently available COVID-19 vaccines. EXPERT OPINION: Booster shots of the current COVID-19 vaccines provide consistently high protection against Omicron-related severe disease and death. Additionally, this protection appears to be conserved for at least 3 months, with a small but significant waning after that. The positive risk-benefit ratio of these vaccines is well established, giving us confidence to administer additional doses as required. Future vaccination strategies will likely include a combination of schedules based on risk profile, as overly frequent boosting may be neither beneficial nor sustainable for the general population.

Reduction in severity and mortality in COVID-19 patients owing to heterologous third and fourth-dose vaccines during the periods of delta and omicron predominance in Thailand.

OBJECTIVES: The COVID-19 pandemic has evolved quickly, with different variants of concern resulting in the need for countries to offer booster vaccinations. Although studies have assessed homologous schedules in detail, the effectiveness of heterologous booster vaccine schedules against severity and mortality with newer variants remains to be explored fully. METHODS: Utilizing a Hospital Information System for COVID-19 established in Chiang Mai, Thailand, we conducted a cohort study by linking patient-level data on laboratory-confirmed COVID-19 cases to the national immunization records, during delta-predominant and omicron-predominant periods. RESULTS: Compared to omicron, COVID-19 cases during the delta period were 10 times more likely to have severe outcomes and in-hospital deaths. During omicron, a third vaccine dose had an 89% reduced risk of both severe COVID-19 and death. The third dose received 14-90 days before the date of the positive test showed the highest protection (93%). Severe outcomes were not observed with the third dose during delta, and the fourth dose during the omicron period. All the vaccine types used for boosting in Thailand offered similar protection against severe COVID-19. CONCLUSION: Booster doses provided a very high level of protection against severe COVID-19 outcomes and deaths. Booster campaigns should focus on improving coverage by utilizing all available vaccines to ensure optimal protection.

Effectiveness of heterologous third and fourth dose COVID-19 vaccine schedules for SARS-CoV-2 infection during delta and omicron predominance in Thailand: a test-negative, case-control study.

Background: The Coronavirus disease 2019 (COVID-19) pandemic has evolved quickly, with numerous waves of different variants of concern resulting in the need for countries to offer continued protection through booster vaccination. To ensure adequate vaccination coverage, Thailand has proactively adopted heterologous vaccination schedules. While randomised controlled trials have assessed homologous schedules in detail, limited data has been reported for heterologous vaccine effectiveness (VE). Methods: Utilising a unique active surveillance network established in Chiang Mai, Northern Thailand, we conducted a test-negative case control study to assess the VE of heterologous third and fourth dose schedules against SARS-CoV-2 infection among suspect-cases during Oct 1-Dec 31, 2021 (delta-predominant) and Feb 1-Apr 10, 2022 (omicron-predominant) periods. Findings: After a third dose, effectiveness against delta infection was high (adjusted VE 97%, 95% CI 94-99%) in comparison to moderate protection against omicron (adjusted VE 31%, 95% CI 26-36%). Good protection was observed after a fourth dose (adjusted VE 75%, 95% CI 71-80%). VE was consistent across age groups for both delta and omicron infection. The VE of third or fourth doses against omicron infection were equivalent for the three main vaccines used for boosting in Thailand, suggesting coverage, rather than vaccine type is a much stronger predictor of protection. Interpretation: Appropriately timed booster doses have a high probability of preventing COVID-19 infection with both delta and omicron variants. Our evidence supports the need for ongoing national efforts to increase population coverage of booster doses. Funding: This research was supported by the National Research Council of Thailand (NRCT) under The Smart Emergency Care Services Integration (SECSI) project to Faculty of Public Health Chiang Mai University.

PrEP stigma among current and non-current PrEP users in Thailand: A comparison between hospital and key population-led health service settings.

Background: Pre-exposure prophylaxis (PrEP) has demonstrated effectiveness in high-risk populations. PrEP service in Thailand became free of charge under the Universal Health Coverage (UHC) in 2021. The National Health Security Office launched a pilot project in 2020 to ensure sustainable service delivery, and the national monitoring and evaluation (M&E) framework was adopted to evaluate early phase implementation. We carried out a cross-sectional survey as part of the M&E process to investigate PrEP stigma among current and non-current PrEP users from both hospital and Key Population Led Health Services (KPLHS) settings in Thailand. Methods: Between August and October 2020, an online cross-sectional survey was conducted. A link for a self-administered questionnaire was distributed to all active PrEP centers and PrEP clients were then recruited by PrEP providers. Descriptive and univariate analysis using Chi-square were applied in the analyses. Attitudes toward PrEP were ranked from the most negative to the most positive. The negative attitude can be interpreted as PrEP stigma. Results: This study included 513 PrEP clients (355 from hospitals and 158 from KPLHS). In both settings, respondents' attitudes toward PrEP were generally positive, but some potential stigma was observed. 31.8% of hospital PrEP clients and 9.5% of KPLHS clients agreed that PrEP users should keep their pills hidden from others. Almost half (44.5%) of hospital clients and 18.4% of KPLHS clients agreed that PrEP users are often viewed negatively by society. More than 20% of hospital clients and 12% of KPLHS agreed that PrEP users frequently experience difficulties when their partner/lover/family find out that he or she is on PrEP. Respondents from the hospitals had slightly higher PrEP stigma than those from KPLHS. Conclusions: According to our findings, at the policy level, the campaign to provide PrEP education to all groups of people should be continued in order to promote a positive view of PrEP and reduce PrEP-related stigma among the general population, which is critical for successful PrEP implementation.

Association between electronic cigarette use and depression among Thai adolescents: The Thailand National Health Examination Survey 2019-2020.

INTRODUCTION: Depression and e-cigarette use among adolescents are two health burdens. However, the association between these dual problems have been less studied, especially in low- and middle-income countries. This study examined the association between depression and e-cigarette use among adolescents in Thailand. METHODS: This cross-sectional study used the sub-sample of the sixth Thai National Health Examination Survey conducted between 2019 and 2020. A total of 4237 adolescents aged 10-19 years were included. Self-reported depression was captured using the 20-item Centre for Epidemiologic Studies Depression Scale (CES-D). We applied a complex survey multiple logistic regression to assess whether e-cigarette use was associated with depression. RESULTS: The mean age of the participants was 14.6 years, 5.3% were ever e-cigarette users, and 2.9% were current e-cigarette users. 37.8% of the participants were categorized at risk for depression. Among e-cigarette users, 51.6% of ever e-cigarette users and 52.9% of current e-cigarette users were at risk for depression. Multiple logistic regression revealed that ever e-cigarette users were at higher risk for depression (AOR=1.66; 95% CI: 1.02-2.71; p=0.042) than never e-cigarette users. Current e-cigarette was not associated with a higher risk for depression (AOR=1.37; 95% CI: 0.77-2.45; p=0.263). CONCLUSIONS: E-cigarette use and depression among adolescents are global public health concerns. There is also a need for effective screening, prevention, and intervention to reduce adverse outcomes of e-cigarette use and depression. In addition, the government should strengthen current policies and close legal loopholes to prevent the tobacco industry tactics and keep e-cigarettes away from adolescents.

Sleep duration and risk of high blood pressure in Thai adolescents: the Thai National Health Examination Survey V, 2014 (NHES-V).

BACKGROUND: Sleep duration has been proposed to be associated with high blood pressure. However, nationwide studies regarding this association in adolescents remain limited. This study aimed to explore the national prevalence of high blood pressure among Thai adolescents and to determine the association between sleep duration and high blood pressure. METHODS: Data from adolescents aged 10-19 years from the Thai National Health and Examination Survey V were included. We collected demographic data (including age and gender), height, weight, waist circumference, blood pressure, fasting blood chemistries and sleep duration data. Sleep durations were categorized as short, normal or long for each age group based on the United States National Sleep Foundation's recommendations. High blood pressure was diagnosed using the 2017 guidelines of the American Academy of Pediatrics. Factors associated with high blood pressure were analyzed using multivariate logistic regression. RESULTS: A total of 3505 adolescents (1785 female) were included. The prevalence of high blood pressure was 9.4% (95% CI 8.5-10.4%). The high blood pressure group had higher BMI z-score, LDL-C, triglyceride and lower HDL-C than the normotensive group. In the multivariate analysis, BMI z-score, LDL-C and HDL-C were independently associated with high blood pressure. However, there was no association between sleep duration and high blood pressure. CONCLUSIONS: High blood pressure risk was increased in adolescents with high BMI z-score. Neither short nor long sleep duration was associated with an increased risk of high blood pressure.