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BACKGROUND: Globally, transgender women have been disproportionately affected by the HIV epidemic, including in Malaysia, where an estimated 11% of transgender women are living with HIV. Available interventions designed specifically to meet transgender women's needs for HIV prevention are limited. Mobile health, particularly smartphone mobile apps, is an innovative and cost-effective strategy for reaching transgender women and delivering interventions to reduce HIV vulnerability. OBJECTIVE: This study aims to adapt a theory-based mobile health HIV prevention smartphone app, HealthMindr, to meet the unique needs of transgender women in Malaysia. We conducted theater testing of the HealthMindr app with transgender women and key stakeholders and explored barriers to transgender women's uptake of HIV pre-exposure prophylaxis (PrEP). METHODS: From February to April 2022, a total of 6 focus group (FG) sessions were conducted with 29 participants: 4 FG sessions with transgender women (n=18, 62%) and 2 FG sessions with stakeholders (n=11, 38%) providing HIV prevention services to transgender women in Malaysia. Barriers to PrEP uptake and gender-affirming care services among transgender women in Malaysia were explored. Participants were then introduced to the HealthMindr app and provided a comprehensive tour of the app's features and functions. Participants provided feedback on the app and on how existing features should be adapted to meet the needs of transgender women, as well as any features that should be removed or added. Each FG was digitally recorded and transcribed. Transcripts were coded inductively using Dedoose software (version 9.0.54; SocioCultural Research Consultants, LLC) and analyzed to identify and interpret emerging themes. RESULTS: Six subthemes related to PrEP barriers were found: stigma and discrimination, limited PrEP knowledge, high PrEP cost, accessibility concerns, alternative prevention methods, and perceived adverse effects. Participants suggested several recommendations regarding the attributes and app features that would be the most useful for transgender women in Malaysia. Adaptation and refinement of the app were related to the attributes of the app (user interface, security, customizable colors, themes, and avatars), feedback, and requests for additional mobile app functional (appointment booking, e-consultation, e-pharmacy, medicine tracker, mood tracker, resources, and service site locator) and communication (peer support group, live chat, and discussion forum) features. CONCLUSIONS: The results reveal that multifaceted barriers hinder PrEP uptake and use among transgender women in Malaysia. The findings also provide detailed recommendations for successfully adapting the HealthMindr app to the context of Malaysian transgender women, with a potential solution for delivering tailored HIV prevention, including PrEP, and increasing accessibility to gender-affirming care services.
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This study investigates the enhancement of the home delivery distribution network for COVID-19 Home Isolation (HI) kits during the Delta variant outbreak of the SARS-CoV-2 virus in Bangkok Metropolitan Area, Thailand. It addresses challenges related to limited resources and delays in delivering HI kits, which can exacerbate symptoms and increase mortality rates. A k-means clustering approach is utilized to optimize the assignment of service areas within the COVID-19 HI program, while discrete event simulation (DES) evaluates potential changes in the home delivery logistics network. Real-world data from the peak outbreak is used to determine the optimal allocation of resources and propose a new logistics network based on proximity to patients' residences. Experimental results demonstrate a significant 44.29 % improvement in overall performance and a substantial 40.80 % decrease in maximum service time. The findings offer theoretical and managerial implications for effective HI management, supporting practitioners and policymakers in mitigating the impact of future outbreaks.
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Condoms continue to be used by many gay, bisexual, and other men who have sex with men (GBM) to reduce the risk of HIV transmission. However this is impacted by condom failure events, defined here as condom breakage and slippage. In a prospective, observational cohort study of 343 HIV serodiscordant male couples recruited through high HIV caseload clinics and hospitals between 2012 and 2016 in Australia, Brazil, and Thailand, condom failure rates and associated factors were analysed, including with the study partner versus other sexual partners. There were 717 reported instances of condom failure from an estimated total of 25,831 sex acts with condoms, from over 588.4 participant years of follow up. Of the HIV-negative partners (n = 343) in the study, more than a third (n = 117, 36.7%) reported at least one instance of condom failure with any partner type during study follow-up. Condom failure with their study partner was reported by 91/343 (26.5%) HIV-negative partners, compared with 43/343 (12.5%) who reported condom failure with other partners. In total, there were 86 events where the HIV-negative partner experienced ano-receptive condom failure with ejaculation, representing 12.0% of all failure events. In multivariable analysis, compared to Australia, HIV-negative men in Brazil reported a higher incidence risk rate of condom failure (IRR = 1.64, 95%CI 1.01-2.68, p = 0.046) and HIV-negative men who reported anal sex with other partners reported an increased risk of condom failure compared with men who only had sex with their study partner (IRR = 1.89, 95%CI 1.08-3.33, p = 0.025). Although at least one event of condom failure was reported by a significant proportion of participants, overall condom failure events represented a small proportion of the total condom protected sex acts.
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Long-acting injectable PrEP, particularly cabotegravir (CAB-LA), has the potential to enhance HIV prevention in Asia, and was the topic of a roundtable held in Singapore in June 2023. Despite proven efficacy, CAB-LA's impact in Asia is hindered by regulatory, manufacturing, and cost barriers. There is an urgent need to address these challenges to expedite CAB-LA's introduction and scale-up, including collaborative research, streamlined regulatory processes, and increased manufacturing capacity. We call for better preparedness in long-acting PrEP in research and implementation science, product licensing and accessibility, and capacity readiness for scale-up, to meet the significant demand among key populations in Asia.
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Fármacos Anti-VIH , Infecciones por VIH , Profilaxis Pre-Exposición , Humanos , Infecciones por VIH/prevención & control , Profilaxis Pre-Exposición/métodos , Asia , Fármacos Anti-VIH/administración & dosificación , Fármacos Anti-VIH/uso terapéutico , Piridonas/administración & dosificación , DicetopiperazinasRESUMEN
INTRODUCTION: Men who have sex with men (MSM), especially those living with HIV, are at an increased risk of anal cancer. The prevalence and incidence of its precursor, anal high-grade squamous intraepithelial lesions (HSILs), among MSM who started antiretroviral therapy during acute HIV acquisition are yet to be explored. METHODS: Participants in an acute HIV acquisition cohort in Bangkok, Thailand, who agreed to take part in this study, were enrolled. All participants were diagnosed and started antiretroviral therapy during acute HIV acquisition. Human papillomavirus (HPV) genotyping and high-resolution anoscopy, followed by anal biopsy as indicated, were done at baseline and 6-monthly visits. RESULTS: A total of 89 MSM and four transgender women were included in the analyses. Median age at enrolment was 26 years. Baseline prevalence of histologic anal HSIL was 11.8%. With a total of 147.0 person-years of follow-up, the incidence of initial histologic anal HSIL was 19.7 per 100 person-years. Factors associated with incident anal HSIL were anal HPV 16 (adjusted hazards ratio [aHR] 4.33, 95% CI 1.03-18.18), anal HPV 18/45 (aHR 6.82, 95% CI 1.57-29.51), other anal high-risk HPV (aHR 4.23, 95% CI 1.27-14.14), syphilis infection (aHR 4.67, 95% CI 1.10-19.90) and CD4 count <350 cells/mm3 (aHR 3.09, 95% CI 1.28-7.48). CONCLUSIONS: With antiretroviral therapy initiation during acute HIV acquisition, we found the prevalence of anal HSIL among cisgender men and transgender women who have sex with men to be similar to those without HIV. Subsequent anal HSIL incidence, although lower than that of those with chronic HIV acquisition, was still higher than that of those without HIV. Screening for and management of anal HSIL should be a crucial part of long-term HIV care for all MSM.
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Infecciones por VIH , Homosexualidad Masculina , Lesiones Intraepiteliales Escamosas , Personas Transgénero , Humanos , Tailandia/epidemiología , Masculino , Adulto , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Infecciones por VIH/complicaciones , Prevalencia , Personas Transgénero/estadística & datos numéricos , Incidencia , Femenino , Homosexualidad Masculina/estadística & datos numéricos , Lesiones Intraepiteliales Escamosas/epidemiología , Lesiones Intraepiteliales Escamosas/patología , Adulto Joven , Neoplasias del Ano/epidemiología , Papillomaviridae/aislamiento & purificación , Papillomaviridae/genética , Infecciones por Papillomavirus/epidemiología , Estudios de Cohortes , Biopsia , Genotipo , Canal Anal/patología , Canal Anal/virologíaRESUMEN
INTRODUCTION: HPTN 083 demonstrated the superiority of long-acting cabotegravir (CAB-LA) versus daily oral emtricitabine/tenofovir disoproxil fumarate (TDF/FTC) as pre-exposure prophylaxis (PrEP) among cisgender men and transgender women who have sex with men (MSM/TGW). HPTN 083 provided the first opportunity to understand experiences with injectable PrEP in a clinical trial. METHODS: Participants from two US sites (Chicago, IL and Atlanta, GA) and one international site (Rio de Janeiro, Brazil) were purposively sampled for individual qualitative interviews (N = 40), between November 2019 and March 2020, to explore trial experiences, barriers to adherence and other factors that may have impacted study implementation or outcomes. The blinded phase ended early due to efficacy; this analysis includes interviews conducted prior to unblinding with three groups defined by adherence (i.e. injection visit attendance): adherent (n = 27), non-adherent (n = 12) and early discontinuers (n = 1). Data were organized using NVivo software and analysed using content analysis. RESULTS: Participants (mean age: 27) were primarily cisgender MSM (90%) and Black/African American (60%). Reasons for trial enrolment and PrEP use included a preference for using HIV prevention medication versus treatment in the event of HIV acquisition; the ability to enhance health via study-related education and services; access to a novel, convenient HIV prevention product at no cost; and contributing to MSM/TGW communities through research. Participants contrasted positive experiences with study staff with their routine clinical care, and emphasized increased scheduling flexibility, thorough communication, non-judgemental counselling and open, affirming environments (e.g. compassion, less stigma) as adherence facilitators. Injection experiences were positive overall; some described early injection-related anxiety, which abated with time and when given some measure of control (e.g. pre-injection countdown), and minimal injection site discomfort. Some concerns and misperceptions about injectable PrEP were reported. Barriers to adherence, across all adherence categories, included structural factors (e.g. financial constraints, travel) and competing demands (e.g. work schedules). CONCLUSIONS: Respondents viewed injectable PrEP trial participation as a positive experience and a means of enhancing wellbeing. Study site flexibility and affirming clinic environments, inclusive of non-judgemental counselling, were key facilitators of adherence. To support injection persistence, interventions that address structural barriers and promote flexible means of injection delivery may be most effective.
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Fármacos Anti-VIH , Infecciones por VIH , Cumplimiento de la Medicación , Profilaxis Pre-Exposición , Humanos , Masculino , Profilaxis Pre-Exposición/métodos , Cumplimiento de la Medicación/estadística & datos numéricos , Infecciones por VIH/prevención & control , Infecciones por VIH/tratamiento farmacológico , Femenino , Fármacos Anti-VIH/administración & dosificación , Fármacos Anti-VIH/uso terapéutico , Adulto , Personas Transgénero/psicología , Homosexualidad Masculina , Adulto Joven , Piridonas/administración & dosificación , Piridonas/uso terapéutico , Brasil , Inyecciones , Piridinas/administración & dosificación , Piridinas/uso terapéutico , Entrevistas como Asunto , Tenofovir/administración & dosificación , Tenofovir/uso terapéutico , Combinación Emtricitabina y Fumarato de Tenofovir Disoproxil/administración & dosificación , Combinación Emtricitabina y Fumarato de Tenofovir Disoproxil/uso terapéutico , Persona de Mediana Edad , DicetopiperazinasRESUMEN
Background: Hepatitis C virus (HCV) coinfection may further compromise immunological and cognitive function in people with HIV (PWH). This study compared laboratory and neuropsychiatric measures across the periods of HCV seroconversion and direct-acting antiviral (DAA) therapy with sustained virologic response (SVR) among PWH who initiated antiretroviral therapy (ART) during acute HIV infection (AHI) and acquired HCV after 24 weeks of ART. Methods: Participants from the RV254 AHI cohort underwent paired laboratory and neuropsychiatric assessments during regular follow-up. The former included measurements of CD4 + and CD8 + T-cell counts, HIV RNA, liver enzymes, and lipid profiles. The latter included the Patient Health Questionnaire-9 (PHQ-9), Distress Thermometer (DT), and a 4-test cognitive battery that evaluated psychomotor speed, executive function, fine motor speed and dexterity. The raw scores in the battery were standardized and averaged to create an overall performance (NPZ-4) score. Parameters of HCV-coinfected participants were compared across HCV seroconversion and DAA treatment groups. Results: Between 2009 and 2022, 79 of 703 RV254 participants acquired HCV after ≥ 24 weeks of ART; 53 received DAA, and 50 (94%) achieved SVR. All participants were Thai males (median age: 30 years); 34 (68%) denied past intravenous drug use, and 41 (82%) had a history of other sexually transmitted infections during follow-up. Following SVR, aspartate transferase (AST) and alanine transaminase (ALT) decreased (p < 0.001), while total cholesterol, low-density lipoprotein, and triglycerides increased (p < 0.01). The median CD4+/CD8 + ratio increased from 0.91 to 0.97 (p = 0.012). NPZ-4 improved from 0.75 to 0.91 (p = 0.004). The median DT score increased from 1.7 to 2.7 (p = 0.045), but the PHQ-9 score remained unchanged. Conclusion: HCV coinfection is common in this group of high-risk PWH, highlighting the need for regular screening, early diagnosis, and treatment. There was a modest improvement in the CD4+/CD8 + T-cell ratio and cognitive performance after DAA therapy in patients who achieved SVR. Future studies should examine potential neuropsychiatric impacts during early HCV infection as well as the longer-term neuropsychiatric outcomes after DAA treatment with SVR.
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HIV is associated with NK cell dysfunction and expansion of adaptive-like NK cells that persist despite antiretroviral therapy (ART). We investigated the timing of NK cell perturbations during acute HIV infection and the impact of early ART initiation. PBMCs and plasma were obtained from people with HIV (PWH; all men who have sex with men; median age, 26.0 y) diagnosed during Fiebig stages I, II, III, or IV/V. Participants initiated ART a median of 3 d after diagnosis, and immunophenotyping was performed at diagnosis and longitudinally after ART. Anti-CMV Abs were assessed by ELISA. Samples from matched HIV-uninfected males were also analyzed. Proportions of adaptive NK cells (A-NKs; defined as Fcε-Receptor-1γ-) were expanded at HIV diagnosis at all Fiebig stages (pooled median 66% versus 25% for controls; p < 0.001) and were not altered by early ART initiation. Abs to CMV immediate early protein were elevated in PWH diagnosed in Fiebig stages III and IV/V (p < 0.03 for both). Proportions of A-NKs defined as either Fcε-Receptor-1γ- or NKG2C+/CD57+ were significantly associated with HIV DNA levels at diagnosis (p = 0.046 and 0.029, respectively) and trended toward an association after 48 wk of ART. Proportions of activated HLA-DR+/CD38+ NK cells remained elevated in PWH despite early ART initiation. NK cell activation and A-NK expansion occur very early after HIV transmission, before T cell activation, and are not altered by ART initiation during acute infection. A-NKs may contribute to HIV control and thus be useful for HIV cure.
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Infecciones por VIH , Células Asesinas Naturales , Humanos , Infecciones por VIH/inmunología , Infecciones por VIH/tratamiento farmacológico , Células Asesinas Naturales/inmunología , Masculino , Adulto , VIH-1/inmunología , Antirretrovirales/uso terapéutico , Inmunidad Adaptativa , Enfermedad Aguda , Adulto JovenRESUMEN
Young MSM (YMSM), aged 15-24, account for nearly half of new HIV infections in Thailand. Pre-exposure prophylaxis (PrEP) is an effective prevention medicine for populations at substantial HIV risk, yet YMSM frequently have suboptimal uptake of and adherence to PrEP. We conducted 35 in-depth interviews with YMSM to explore barriers and facilitators of both PrEP initiation and adherence. Interviews also elicited the perceptions and experiences of healthcare providers (HCPs) working with YMSM at three clinics in Bangkok. Primary barriers to PrEP initiation were limited accessibility, insufficient knowledge, and efficacy concerns; HCPs identified no-to-low self-perception of HIV risk, pre-existing health problems, fears of side effects, and living in distant provinces as barriers to PrEP initiation. YMSM primarily reported PrEP information and self-perceptions of elevated HIV risk as facilitators to PrEP initiation. Additionally, forgetfulness and low HIV risk awareness were common barriers to PrEP adherence. Reminders were a prominent facilitator of PrEP adherence alongside disclosure to close relationships, the routinization of regimens, and convenient facilities. HCPs regarded counseling as the leading facilitator of PrEP adherence. By understanding the barriers/facilitators of PrEP use, the current study seeks to help develop evidence-informed PrEP intervention programs among YMSM while considering cultural sensitivity.
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Fármacos Anti-VIH , Infecciones por VIH , Conocimientos, Actitudes y Práctica en Salud , Homosexualidad Masculina , Cumplimiento de la Medicación , Profilaxis Pre-Exposición , Investigación Cualitativa , Humanos , Masculino , Tailandia , Infecciones por VIH/prevención & control , Homosexualidad Masculina/psicología , Adulto Joven , Cumplimiento de la Medicación/psicología , Adolescente , Fármacos Anti-VIH/uso terapéutico , Entrevistas como Asunto , Adulto , Aceptación de la Atención de Salud/psicología , Aceptación de la Atención de Salud/estadística & datos numéricos , Personal de Salud/psicologíaRESUMEN
BACKGROUND: Transgender women (TGW) are disproportionately affected by HIV, and HIV prevalence among TGW in Thailand has been increasing. Although oral daily pre-exposure prophylaxis (PrEP) is effective for HIV prevention, PrEP uptake and persistence among TGW have been low. This study aimed to provide a deeper understanding of TGW's experiences with PrEP uptake and adherence, and to identify major barriers to PrEP use to inform intervention adaptation. METHODS: We interviewed 20 young TGW (six non-PrEP users, eight adherent, six non-adherent) and 10 health care providers from two HIV clinics in Bangkok, Thailand, in 2022. We focused on understanding challenges to PrEP use in this population using an interview guide based on a theoretical model of behaviour change and thematic content analysis. RESULTS: Thematic analysis identified major barriers to and facilitators of PrEP uptake and adherence. Barriers to PrEP initiation included low self-perceived HIV risk, concern about potential side-effects, patient burdens such as frequent HIV testing for prescription refills and social stigma against PrEP. Barriers to adherence included side-effects, inconvenient access to health services (especially during COVID-19 lockdowns), forgetfulness resulting from busy schedules and low self-perceived HIV risk. TGW also reported health care providers' stigma against PrEP users deterred them from seeking further PrEP services. TGW identified major facilitators of PrEP initiation, including awareness about the benefits of PrEP, concern about risks of HIV and supportive social networks of PrEP users. As to PrEP regimens, most TGW participants reported a clear preference for long-lasting, injectable PrEP over daily oral PrEP. TGW and health care providers largely agreed on barriers and facilitators of PrEP use, but they differed in perceptions of HIV risk. CONCLUSIONS: The results highlighted challenges and opportunities to improve the delivery of PrEP, as well as other sexually transmissable infection and mental health services, especially among TGW. Thus, there is an urgent need for developing effective intervention programs that could raise PrEP awareness and knowledge, reduce PrEP stigma, and improve PrEP delivery systems among TGW in Thailand.
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Fármacos Anti-VIH , Infecciones por VIH , Profilaxis Pre-Exposición , Personas Transgénero , Masculino , Humanos , Femenino , Homosexualidad Masculina/psicología , Infecciones por VIH/tratamiento farmacológico , Profilaxis Pre-Exposición/métodos , Personas Transgénero/psicología , Tailandia , Fármacos Anti-VIH/uso terapéuticoRESUMEN
BACKGROUND AND AIMS: Health inequities related to alcohol use exist for transgender individuals. While the Thailand Ministry of Public Health recently published a clinical guideline to implement a Screening, Brief Intervention and Referral to Treatment (SBIRT) in primary care, there has been no study regarding transgender women's (TGW) alcohol use and the acceptability of implementing SBIRT in a Thai context, a gap this study aimed to fill. DESIGN: A mixed-method approach was used. In the first phase, TGW service users and health-care providers (HCPs) completed a survey on the acceptability of prospective implementation of SBIRT. TGW service users completed the Alcohol Use Disorder Identification Test-Consumption (AUDIT-C). In the second phase, TGW service users, HCPs, clinic administrators and national-level alcohol, HIV and transgender health policymakers participated in in-depth qualitative interviews. SETTING: The Tangerine Clinic, a transgender-led sexual health clinic in Bangkok, Thailand. PARTICIPANTS: In the first phase, TGW service users (n = 100) and HCP (n = 8) were surveyed. In the second phase, 22 stakeholders (n = 10 TGW service users; n = 8 HCP; n = 1 clinic administrator; n = 3 policymakers) were interviewed. MEASUREMENTS: Simple proportions were calculated for each survey item. Differences in acceptability by various demographic factors were calculated using univariate analysis. The qualitative data were coded using thematic analysis and a deductive approach. The results were mapped to the Consolidated Framework for Implementation Research domains and constructs. The quantitative and qualitative results were triangulated to expand understanding. FINDINGS: Fifty per cent of the TGW participants exhibited problematic drinking levels (AUDIT-C ≥ 4). Implementing SBIRT was highly acceptable, as more than 95% of participants reported agreeing or completely agreeing to receive SBIRT for alcohol use. Barriers, such as complexity, time constraint and lack of knowledge and skills, were anticipated. Adaptability, such as tailoring the content of brief intervention to suit TGW health needs and SBIRT to fit with existing clinic procedures, might facilitate successful implementation. CONCLUSION: Screening, Brief Intervention and Referral to Treatment (SBIRT) for alcohol use has the potential to be successfully implemented in transgender-led sexual health clinic settings, with some adaptations to overcome anticipated barriers.
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Trastornos Relacionados con Sustancias , Personas Transgénero , Humanos , Femenino , Intervención en la Crisis (Psiquiatría) , Trastornos Relacionados con Sustancias/terapia , Tailandia , Estudios Prospectivos , Etanol , Derivación y Consulta , Tamizaje Masivo/métodosRESUMEN
BACKGROUND: Men who have sex with men (MSM) in the Asia-Pacific region have a disproportionately high burden of HIV infection compared with the general population. Although pre-exposure prophylaxis (PrEP) for HIV is highly effective at preventing new HIV infections, the cost-effectiveness of PrEP for MSM in different countries in the Asia-Pacific region with varying PrEP coverage and HIV testing frequencies remains unstudied. We aimed to analyse the economic and health benefits of long-acting injectable cabotegravir (CAB-LA) compared with oral PrEP in high-income countries and low-income and middle-income countries within the Asia-Pacific region. METHODS: We developed a decision-analytic Markov model to evaluate the population impact and cost-effectiveness of PrEP scale-up among MSM in Australia, Thailand, and China. We assumed a static cohort of 100â000 MSM aged 18 years or older who were at risk of HIV infection, with a monthly cycle length over a 40-year time period. We evaluated hypothetical scenarios with universal PrEP coverage of 80% among 100â000 suitable MSM in each country. We modelled oral PrEP and CAB-LA for MSM with diverse HIV testing frequency strategies. We adopted the health-care system's perspective with a 3% annual discount rate. We calculated the incremental cost-effectiveness ratio (ICER), measured as additional cost per quality-adjusted life-year (QALY) gained, to compare different strategies with the status quo in each country. All costs were reported in 2021 US$. We also performed one-way, two-way, and probabilistic sensitivity analyses to assess the robustness of our findings. FINDINGS: Compared with the status quo in each country, expanding oral PrEP to 80% of suitable MSM would avert 8·1% of new HIV infections in Australia, 14·5% in Thailand, and 26·4% in China in a 40-year period. Expanding oral PrEP use with 6-monthly HIV testing for both PrEP and non-PrEP users was cost-saving for Australia. Similarly, expanding oral PrEP use remained the most cost-effective strategy in both Thailand and China, but optimal testing frequency varied, with annual testing in Thailand (ICER $4707 per QALY gained) and 3-monthly testing in China (ICER $16â926 per QALY gained) for both PrEP and non-PrEP users. We also found that replacing oral PrEP with CAB-LA for MSM could avert more new HIV infections (12·8% in Australia, 27·6% in Thailand, and 32·8% in China), but implementing CAB-LA was not cost-effective due to its high cost. The cost of CAB-LA would need to be reduced by 50-90% and be used as a complementary strategy to oral PrEP to be cost-effective in these countries. INTERPRETATION: Expanding oral PrEP use for MSM, with country-specific testing frequency, is cost-effective in Australia, Thailand, and China. Due to the high cost, CAB-LA is currently not affordable as a single-use strategy but might be offered as an additional option to oral PrEP. FUNDING: Ministry of Science and Technology of the People's Republic of China, the Australian National Health and Medical Research Council, National Key Research and Development Program of China, and National Natural Science Foundation of China.
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Fármacos Anti-VIH , Infecciones por VIH , Profilaxis Pre-Exposición , Minorías Sexuales y de Género , Masculino , Humanos , Infecciones por VIH/diagnóstico , Infecciones por VIH/prevención & control , Infecciones por VIH/tratamiento farmacológico , Homosexualidad Masculina , Fármacos Anti-VIH/uso terapéutico , Análisis de Costo-Efectividad , Tailandia , Análisis Costo-Beneficio , Australia/epidemiología , China/epidemiologíaRESUMEN
OBJECTIVE: HIV-associated neuroinflammation persists in the brain despite suppressive combination antiretroviral therapy (cART). We evaluated associations between a subset of CD8 + T cells, termed CD4 dim CD8 bright T cells, and soluble markers of immune activation and/or neuroinflammation in the cerebrospinal fluid (CSF) and plasma of people with HIV (PWH). DESIGN: Fifteen cART-naive PWH were enrolled and underwent blood draw, lumbar puncture for CSF collection, and neuropsychological tests at week 0 (pre-cART) and 24âweeks after cART initiation. METHODS: CSF and peripheral blood T cells were evaluated with flow cytometry and soluble markers of immune activation were measured by multiplex and singleplex assays. Spearman bootstrap correlation coefficients with 10â000 resamples were computed and reported with corresponding 95% confidence intervals (CIs) for each marker of interest and T-cell type. RESULTS: The frequency of CSF CD4 dim CD8 bright T cells at week 0 was inversely related with CSF neopterin. In contrast, at week 24, CSF CD4 - CD8 + T cells were positively correlated with CSF s100ß, a marker of brain injury. In the blood, at week 0, CD4 dim CD8 bright T cells were inversely correlated with MCP-1, IP-10, IL-8, IL-6, G-CSF, and APRIL and positively correlated with plasma RANTES and MMP1. At week 0, the frequency of blood CD4 - CD8 + were positively correlated with CRP and BAFF. CONCLUSION: CD4 dim CD8 bright T cells are associated with some anti-inflammatory properties, whereas CD4 - CD8 + T cells may contribute to inflammation and injury. Assessing the contrast between these two cell populations in neuroHIV may inform targeted therapeutic intervention to reduce neuroinflammation and associated neurocognitive impairment.