Drug-drug Interactions Among Thai Transgender Women Living with Human Immunodeficiency Undergoing Feminizing Hormone Therapy and Antiretroviral Therapy: The iFACT Study.

BACKGROUND: Drug-drug interactions between feminizing hormone therapy (FHT) and antiretroviral therapy (ART) are a major concern among transgender women (TGW), which may lead to suboptimal ART adherence and inappropriate FHT dosage. To evaluate potential drug-drug interactions between FHT and ART, we performed intensive measurements of the pharmacokinetic (PK) parameters of blood tenofovir (TFV), efavirenz (EFV), and estradiol (E2). METHODS: Twenty TGW with newly diagnosed human immunodeficiency virus (HIV) infection were enrolled. FHT (E2 valerate 2 mg/d and cyproterone acetate 25 mg/d) was prescribed at baseline until week 5 and restarted at week 8. ART (TFV disoproxil fumarate/emtricitabine/EFV at 300/200/600 mg) was initiated at week 3. The E2 PK parameters were measured intensively at weeks 3 (without ART) and 5 (with ART), and TFV and EFV PK parameters were measured intensively at weeks 5 (with FHT) and 8 (without FHT). RESULTS: The median (interquartile range) age and body mass index were 25.5 (22.5-31.0) years and 20.6 (19.3-23.1) kg/m2, respectively. The differences in geometric mean ratios between weeks 3 and 5 were as follows for E2 area under the curve, maximum concentration, and concentration at 24 hours (C24), respectively: 0.72 (90% confidence interval, .64-.81; P < .001), 0.81 (.72-.92; P = .006), and 0.64 (.50-.83; P = .004). The differences in geometric mean ratios between weeks 5 and 8 were as follows for TFV AUC, TFV C24, and EFV C24: 0.86 (90% confidence interval, .80-.93; P = .002), 0.83 (.75-.93; P = .006), and 0.91 (.85-.97; P = .02). CONCLUSIONS: Among HIV-positive TGW, E2 PK parameters were significantly lower in the presence of TFV disoproxil fumarate/emtricitabine/EFV, and some TFV and EFV PK parameters were lower in the presence of FHT. Further studies should determine whether these reductions are clinically significant and whether they occur with other FHT or ART regimens.

What will it take to end AIDS in Asia and the Pacific region by 2030?

The 2016 global commitments towards ending the AIDS epidemic by 2030 require the Asia-Pacific region to reach the Fast-Track targets by 2020. Despite early successes, the region is well short of meeting these targets. The overall stalled progress in the HIV response has been further undermined by rising new infections among young key populations and the unprecedented COVID-19 pandemic. This paper examines the HIV situation, assesses the gaps, and analyses what it would take the region to end AIDS by 2030. Political will and commitments for ending AIDS must be reaffirmed and reinforced. Focused regional strategic direction that answers the specific regional context and guides countries to respond to their specific needs must be put in place. The region must harness the power of innovative tools and technology in both prevention and treatment. Community activism and meaningful community engagement across the spectrum of HIV response must be ensured. Punitive laws, stigma, and discrimination that deter key populations and people living with HIV from accessing health services must be effectively tackled. The people-centred public health approach must be fully integrated into national universal health coverage while ensuring domestic resources are available for community-led service delivery. The region must utilise its full potential and draw upon lessons that have been learnt to address common challenges of the HIV and COVID-19 pandemics and achieve the goal of ending AIDS by 2030, in fulfillment of the United Nations' Sustainable Development Goals.

Demedicalisation of HIV interventions to end HIV in the Asia-Pacific.

Despite the challenges to the HIV response in the Asia-Pacific, a demedicalisation of HIV intervention has been demonstrated to be an important strategy to maximise the uptake of HIV prevention tools among key populations in this region. Demedicalisation of HIV interventions translates medical discourse and shifts the paradigm from a disease-focused to a people-centred approach. It also recognises real-life experiences of key populations in the HIV response by empowering them to voice their needs and be at the forefront of the epidemic control. We further categorise a demedicalisation approach into three frameworks: (1) the demystification of clinical or medical concerns; (2) the destigmatisation of people living with HIV; and (3) the decentralisation of healthcare services. This article reviewed the demedicalisation framework by looking at the HIV intervention examples from countries in the Asia-Pacific, which included: (1) a study on drug-drug interaction between pre-exposure prophylaxis and feminising hormone treatment for transgender women; (2) the roles of key population-led health services; and (3) certification of key population lay providers.

High burden of chlamydia and gonorrhoea in pharyngeal, rectal and urethral sites among Thai transgender women: implications for anatomical site selection for the screening of STI.

OBJECTIVE: Comprehensive data on Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections to guide screening services among transgender women (TGW) are limited. We studied the burden of CT/NG infections in pharyngeal, rectal and urethral sites of Thai TGW and determined missed CT/NG diagnoses if selected site screening was performed. METHODS: Thai TGW were enrolled to the community-led test and treat cohort. CT/NG screening was performed from pharyngeal swab, rectal swab and urine using nucleic acid amplification test. CT/NG prevalence in each anatomical site was analysed, along with the relationships of CT/NG among the three anatomical sites. RESULTS: Of 764 TGW included in the analysis, 232 (30.4%) had CT/NG infections at any anatomical site, with an overall incidence of 23.7 per 100 person-years. The most common CT/NG infections by anatomical site were rectal CT (19.5%), rectal NG (9.6%) and pharyngeal NG (8.1%). Among 232 TGW with CT/NG infections at any anatomical site, 22%-94.4% of infections would have been missed if single anatomical site testing was conducted, depending on the selected site. Among 668 TGW who tested negative at pharyngeal site, 20.4% had either rectal or urethral infections. Among 583 TGW who tested negative at the rectal site, 8.7% had either pharyngeal or urethral infections. Among 751 TGW who tested negative at the urethral site, 19.2% had either pharyngeal or rectal infections. CONCLUSION: Almost one-third of Thai TGW had CT/NG infections. All-site screening is highly recommended to identify these infections, but if not feasible rectal screening provides the highest yield of CT/NG diagnoses. Affordable molecular technologies and/or CT/NG screening in pooled samples from different anatomical sites are urgently needed. TRIAL REGISTRATION NUMBER: NCT03580512.

Correlates of nonadherence to key population-led HIV pre-exposure prophylaxis services among Thai men who have sex with men and transgender women.

BACKGROUND: Based on government estimates from the Asian Epidemic Model, new infections among men who have sex with men (MSM) and transgender women (TGW) in Thailand are forecast to proportionally increase over time. Daily oral Pre-exposure prophylaxis (PrEP) protects against HIV acquisition when used as prescribed. The "Princess PrEP" program is the first key population-led (PrEP) initiative under Thai royal patronage with an aim to scale up countrywide implementation of PrEP. METHODS: Retention in and adherence to key population-led HIV PrEP services among HIV-uninfected Thai MSM and TGW was examined in four provinces: Bangkok, Chonburi, Chiang Mai, and Songkhla. HIV, HBsAg, creatinine tests, and self-administered questionnaires were performed during baseline measures. Participants were followed up after month 1, at month 3, then every 3 months. Correlates of nonadherence and loss to follow up at 1 month were assessed using linear regression models. RESULTS: 37.4% of the participants reported low adherence to services (≤ 3 pills/week or missed clinic schedule at month 1). Factors associated with low adherence included younger age (25 years and under) (adjusted odds ratio (aOR): 1.49, 95% confidence interval (95% CI: 1.01-2.21, p = 0.044), being a TGW (aOR: 2.2, 95% CI: 1.27-3.83, p = 0.005), and whether the participant had not previously accessed services at the clinic (aOR = 1.68, 95% CI: 1.03-2.76, p = 0.04). Additionally, participants in Chonburi (the only TGW site) showed significantly lower adherence than those in the other three provinces (aOR: 2.91, 95% CI: 1.55-5.45, p = 0.001). CONCLUSION: Urgent, innovative interventions for early PrEP adherence support among vulnerable sub-populations such as younger users, TGW, and new clients are needed to maximize prevention strategy in Thailand.

HIV prevalence and incidence among men who have sex with men and transgender women in Bangkok, 2014-2018: Outcomes of a consensus development initiative.

To reach its goal of ending AIDS by 2030, Thailand has adopted antiretroviral treatment as prevention and HIV pre-exposure prophylaxis for men who have sex with men (MSM) and transgender women (TGW) as its core HIV control strategy. However, in the absence of reliable epidemiologic indicators, the impact of these policies on the course of the HIV epidemic in these groups remains unknown. To help answer this question, we formulated an HIV epidemic consensus initiative for Bangkok, Thailand, to analyze epidemiologic and program data and reach agreement between experts and stakeholders on the evolving state of the HIV epidemic among MSM and TGW. A customized Delphi process was used to consult and consolidate viewpoints of experts and stakeholders. Experts presented and discussed HIV prevalence and incidence data from recent and ongoing studies among MSM and TGW in Bangkok (2014 to 2018) during a meeting with stakeholders representing government, donors, and civil society. Agreement about the course of the HIV epidemic among MSM and TGW was attained by voting consensus. Based on presented data, meeting participants agreed that HIV prevalence and incidence had decreased among Bangkok MSM from 2014 to 2018. Despite these declines, HIV prevalence and incidence were found to remain high. This was particularly the case among younger MSM. Participants agreed that there was no evidence for a decrease in HIV prevalence and incidence among Bangkok TGW. Introduction of antiretroviral treatment as prevention and HIV pre-exposure prophylaxis may have contributed to these declines. However, HIV prevalence and incidence remained high, and no signs of a decrease were reported among Bangkok TGW. At the current rate of new HIV infections in MSM and TGW, Thailand will not reach its goal of ending AIDS by 2030. This HIV consensus initiative may serve as a model for building agreement and advocacy on epidemiologic and program data and their implications for a large metropolitan city.

Uptake of oral fluid-based HIV self-testing among men who have sex with men and transgender women in Thailand.

BACKGROUND: Suboptimal uptake of HIV testing remains a primary bottleneck to HIV prevention and treatment for men who have sex with men (MSM) and transgender women (TGW) in Thailand. The World Health Organization has recommended HIV self-testing (HIVST) as an additional strategic HIV service. However, HIVST has not been fully endorsed and implemented in many countries in Southeast Asia. The aim of this study was to assess the uptake of oral fluid-based HIVST in MSM and TGW populations in Thailand. METHODS: During 2017 and 2018, we conducted a cross-sectional study using convenience sampling to enroll 2,524 participants from three major urban areas. Participants were recruited during outreach and online activities and were offered unassisted or assisted HIVST, or referral to HIV testing services. A descriptive analysis was performed for summarizing data. RESULTS: A total of 2,502 participants (1,422 MSM and 1,082 TGW) were included in the analysis with about one-third (36.1%) of them being first-time testers. Among all participants enrolled in the study, a total of 2,486 participants (99.3%) selected HIVST versus referral to HIV testing services. Of those who selected HIVST, 2,095 (84.3%) opted for assisted HIVST while the rest opted for unassisted HIVST: 1,148 of 1,411 MSM (81.4%) and 947 of 1,075 TGW (88.1%) selected assisted HIVST. While no serious adverse events were reported during the study, we found that among 179 participants who needed a confirmatory test and were referred to HIV testing services, 108 (60.3.4%) accessed these later services. CONCLUSIONS: This study demonstrated a high uptake of oral fluid-based HIVST among MSM and TGW populations in Thailand and that HIVST could be scaled up through the national epidemic control program. However, a better understanding of HIV testing-seeking behavior and innovative follow-up solutions are needed to improve and monitor linkages to services for people who undertake HIVST.

Fast-tracking the end of HIV in the Asia Pacific region: domestic funding of key population-led and civil society organisations.

Ending AIDS in Asia Pacific by 2030 requires countries to give higher priority to financing community-based and key population-led service delivery. Mechanisms must be developed for civil society organisations to deliver health and HIV/AIDS services for key populations, especially men who have sex with men, and transgender people, within national health policy frameworks. Current investments in the HIV response in the Asia Pacific region reflect inadequate HIV financing for key populations, particularly for civil society and key population-led organisations that are optimally positioned to advance HIV epidemic control. These organisations are typically supported by international agencies whose investments are starting to decline. Domestic investments in key population-led organisations are often hampered by punitive laws against their communities, pervasive stigma and discrimination by policy makers, an insufficient understanding of the most effective HIV epidemic control strategies, and financing systems that limit access to funding for these organisations from the national budget. Countries in the Asia Pacific region are evolving their community-based and key population policies and programmes. We need accessible, disaggregated financial data and in-depth case studies that showcase effective key population-led programmes, to enable countries to learn from each other.

Evaluation of a pre-exposure prophylaxis programme for men who have sex with men and transgender women in Thailand: learning through the HIV prevention cascade lens.

INTRODUCTION: Men who have sex with men (MSM) and transgender women (TGW) are two key populations (KPs) in Thailand at high risk for HIV. Uptake and scale-up of pre-exposure prophylaxis (PrEP) among them has been slow. We used data from Princess PrEP, Thailand's largest KP-led PrEP programme, to operationalize PrEP service cascades. We identified gaps and pointed out where additional data are needed to inform a larger HIV prevention cascade. METHODS: Numbers of people tested for HIV, tested HIV negative, eligible for PrEP (defined as any of the following in the past three months: condomless sex with partners of unknown/uncertain HIV status or antiretroviral treatment or viral load status, multiple partners, engaging in sex work, sexually transmitted infections, injecting drugs, using amphetamine-type stimulants, or repeated use of post-exposure prophylaxis), offered PrEP and accepted PrEP during January to November 2019 were retrieved from Princess PrEP database to inform PrEP service cascades for MSM and TGW. Reasons for not accepting PrEP were documented. RESULTS: Of 6287 MSM who received HIV testing in Princess PrEP, 92.3% were HIV negative and 70.2% of them were eligible for PrEP. PrEP was offered to 94.7% of those eligible and 48.0% of those offered accepted it. Among 900 TGW who had HIV testing, 95.3% tested HIV negative and 64.8% of them met PrEP eligibility criteria. Of these, 95.0% were offered PrEP and 43.9% of them accepted it. Among MSM and TGW who met PrEP eligibility criteria, no or low-HIV-risk perception was the most common reason provided (46.7% of 2007 MSM and 41.9% of 296 TGW) for not accepting PrEP. CONCLUSIONS: PrEP service cascades from the Princess PrEP programme identified no or low-risk perception as key barrier to PrEP acceptance among MSM and TGW who met PrEP eligibility criteria. More implementation research studies are needed to explore PrEP motivation and access in larger communities outside of clinical services. This is to identify gaps and strategies to address them within motivation, access and effective use domains of the HIV prevention cascade.

Correlations of chlamydia and gonorrhoea among pharyngeal, rectal and urethral sites among Thai men who have sex with men: multicentre community-led test and treat cohort in Thailand.

OBJECTIVE: Routine screening for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections in sexually exposed anatomical sites may be challenging in resource-limited settings. The objective of this study was to determine the proportion of missed CT/NG diagnoses if a single anatomical site screening was performed among men who have sex with men (MSM) by examining the pattern of anatomical sites of CT/NG infections. METHODS: Thai MSM were enrolled to the community-led test and treat cohort. Screening for CT/NG infections was performed from pharyngeal swab, rectal swab and urine using nucleic acid amplification testing. The correlations of CT/NG among the three anatomical sites were analysed. RESULTS: Among 1610 MSM included in the analysis, 21.7% had CT and 15.5% had NG infection at any anatomical site. Among those tested negative for CT or NG infection at either pharyngeal, rectal or urethral site, 8%-19% had CT infection and 7%-12% had NG infection at the remaining two sites. Of the total 349 CT infections, 85.9%, 30.6% and 67.8% would have been missed if only pharyngeal, rectal or urethral screening was performed, respectively. Of the total 249 NG infection, 55.7%, 39.6% and 77.4% would have been missed if only pharyngeal, rectal or urethral screening was performed, respectively. The majority of each anatomical site of CT/NG infection was isolated to their respective site, with rectal site having the highest proportion of isolation: 78.9% of rectal CT and 62.7% of rectal NG infection. CONCLUSIONS: A high proportion of CT/NG infections would be missed if single anatomical site screening was performed among MSM. All-site screening is highly recommended, but if not feasible, rectal screening provides the highest yield of CT/NG diagnoses. Effort in lowering the cost of the CT/NG screening test or developing affordable molecular technologies for CT/NG detection is needed for MSM in resource-limited settings. TRIAL REGISTRATION NUMBER: NCT03580512; Results.

Drug-drug interactions between feminizing hormone therapy and pre-exposure prophylaxis among transgender women: the iFACT study.

INTRODUCTION: Concerns over potential drug-drug interactions (DDI) between feminizing hormone therapy (FHT) and pre-exposure prophylaxis (PrEP) have hampered uptake and adherence of PrEP among transgender women (TGW). To determine DDI between FHT and PrEP, we measured the pharmacokinetic (PK) parameters of blood plasma estradiol (E2) and tenofovir (TFV) in Thai TGW. METHODS: Twenty TGW who never underwent orchiectomy and had not received injectable FHT within six months were enrolled between January and March 2018. FHT (E2 valerate and cyproterone acetate) were prescribed to participants at baseline until week 5, and then from week 8 until the end of study. Daily PrEP (tenofovir disoproxil fumarate/emtricitabine) was initiated at week 3 and continued without interruption. Intensive E2 PK parameters and testosterone concentration at 24 hours (C24 ) were measured at weeks 3 (without PrEP) and 5 (with PrEP), and intensive TFV PK parameters were measured at weeks 5 (with FHT) and 8 (without FHT). RESULTS: Median (interquartile range) age, body mass index, and creatinine clearance were 21.5 (21-26) years, 20.6 (19.0-22.4) kg/m2 , and 116 (101-126.5) mL/min, respectively. The geometric mean (%CV) of area under curve from time zero to 24 hours (AUC0-24 ), maximum concentration (Cmax ), and C24 of E2 at weeks 3 and 5 were 775.13 (26.2) pg h/mL, 51.47 (26.9) pg/mL, and 15.15 (42.0) pg/mL; and 782.84 (39.6), 55.76 (32.9), and 14.32 (67.4), respectively. The geometric mean (%CV) of TFV AUC0-24 , Cmax , and C24 at weeks 5 and 8 were 2242.1 (26.5) ng h/mL, 353.9 (34.0) ng/mL, and 40.9 (31.4) ng/mL; and 2530.2 (31.3), 311.4 (30.0), and 49.8 (29.6), respectively. The geometric mean of TFV AUC0-24 and C24 at week 5 were significantly less than that at week 8 by 12% (p = 0.03) and 18% (p < 0.001), respectively. There were no significant changes in E2 PK parameters and median C24 of bioavailable testosterone between week 3 and week 5. CONCLUSIONS: Our study demonstrated lower blood plasma TFV exposure in the presence of FHT, suggesting that FHT may potentially affect PrEP efficacy among TGW; but E2 exposure was not affected by PrEP. Further studies are warranted to determine whether these reductions in TFV are clinically significant. Clinical Trial Number: NCT03620734.

Characteristics and HIV epidemiologic profiles of men who have sex with men and transgender women in key population-led test and treat cohorts in Thailand.

Men who have sex with men (MSM) and Transgender Women (TGW) in Thailand contribute to more than half of all new HIV infections annually. This cross-sectional study describes epidemiologic profiles of these key populations (KP) in Key Population-led Test and Treat study. Baseline data were collected using self-administered questionnaires and HIV/STI testing from MSM and TGW aged ≥18 years enrolled in a cohort study in six community sites in Thailand between October 2015 and February 2016. Factors associated with HIV prevalence were determined by logistic regression. TGW in the cohorts had lower education and income levels than MSM. TGW also engaged in sex work more, though similar proportions between MSM and TGW reported to have multiple sexual partners and STI diagnosis at baseline. HIV prevalence was 15.0% for MSM and 8.8% for TGW in the cohorts. HIV prevalence among TGW was more associated with sociodemographic characteristics, whereas factors related to behavioral risks were determined to be associated with HIV prevalence among MSM. TGW and MSM in the cohorts also had high prevalence of STI. Key Population-driven HIV services are able to capture harder-to-reach key populations who are at heightened risk for HIV.

Princess PrEP program: the first key population-led model to deliver pre-exposure prophylaxis to key populations by key populations in Thailand.

Background No data are available on the feasibility of pre-exposure prophylaxis (PrEP) delivered by trained key population (KP) community health workers. Herein we report data from the KP-led Princess PrEP program serving men who have sex with men (MSM) and transgender women (TGW) in Thailand. METHODS: From January 2016 to December 2017, trained MSM and TGW community health workers delivered same-day PrEP service in community health centres, allowing clients to receive one PrEP bottle to start on the day of HIV-negative testing. Visits were scheduled at Months 1 and 3, and every 3 months thereafter. Uptake, retention and adherence to PrEP services and changes in risk behaviours over time are reported. RESULTS: Of 1467 MSM and 230 TGW who started PrEP, 44.1% had had condomless sex in the past 3 months. At Months 1, 3, 6, 9 and 12, retention was 74.2%, 64.0%, 56.2%, 46.7% and 43.9% respectively (lower in TGW than MSM at all visits; P<0.001), with adherence to at least four PrEP pills per week self-reported by 97.4%, 96.8%, 96.5%, 97.5% and 99.5% of respondents respectively (no difference between MSM and TGW). Logistic regression analysis identified age >25 years, being MSM and having at least a Bachelors degree significantly increased retention. Condomless sex did not change over the 12-month period (from 47.2% to 45.2%; P=0.20). New syphilis was diagnosed in 4.9% and 3.0% of PrEP clients at Months 6 and 12 (cf. 7.0% at baseline; P=0.007). Among PrEP adherers and non-adherers, there were one and six HIV cases of seroconversion respectively, which resulted in corresponding HIV incidence rates (95% confidence interval) of 0.27 (0.04-1.90) and 1.36 (0.61-3.02) per 100 person-years. CONCLUSION: Our KP-led PrEP program successfully delivered PrEP to MSM and TGW. Innovative retention supports are needed, especially for TGW and those who are young or with lower education levels. To scale-up and sustain KP-led PrEP programs, strong endorsement from international and national guidelines is necessary.

Importance of Risk Perception: Predictors of PrEP Acceptance Among Thai MSM and TG Women at a Community-Based Health Service.

BACKGROUND: HIV prevalence among Thai men who have sex with men (MSM) and transgender women (TG) are 9.15% and 11.8%, respectively, compared with 1.1% in the general population. To better understand early adopters of pre-exposure prophylaxis (PrEP) in Thailand, we analyzed biobehavioral and sociodemographic characteristics of PrEP-eligible MSM and TG. SETTING: Four Thai urban community clinics between October 2015 and February 2016. METHODS: Sociodemographics, HIV risk characteristics, and PrEP knowledge and attitudes were analyzed in association with PrEP initiation among eligible Thai MSM and TG. Adjusted analysis explored factors associated with PrEP acceptance. We then analyzed HIV risk perception, which was strongly associated with PrEP initiation. RESULTS: Of 297 participants, 55% accepted PrEP (48% of MSM, 54% of TG). Perceived HIV risk levels were associated with PrEP acceptance [odds ratio (OR): 4.3; 95% confidence interval (95% CI): 1.5 to 12.2. OR: 6.3; 95% CI: 2.1 to 19.0. OR: 14.7; 95% CI: 3.9 to 55.1; for minimal, moderate, and high perceived risks, respectively]. HIV risk perception was associated with previous HIV testing (OR: 2.2; 95% CI: 1.4 to 3.5); inconsistent condom use (OR: 1.8; 95% CI: 1.1 to 2.9); amphetamine use in the past 6 months (OR: 3.1; 95% CI: 1.1 to 8.6); and uncertainty in the sexually transmitted infection history (OR: 2.3; 95% CI: 1.4 to 3.7). Approximately half of those who reported either inconsistent condom use (46%), multiple partners (50%), group sex (48%), or had baseline bacterial sexually transmitted infection (48%) perceived themselves as having no or mild HIV risk. CONCLUSIONS: HIV risk perception plays an important role in PrEP acceptance. Perception does not consistently reflect actual risk. It is therefore critical to assess a client's risk perception and provide education about HIV risk factors that will improve the accuracy of perceived HIV risk.