Radiation therapy for ventricular arrhythmias.

Ventricular arrhythmias (VA) can be life-threatening arrhythmias that result in significant morbidity and mortality. Catheter ablation (CA) is an invasive treatment modality that can be effective in the treatment of VA where medications fail. Recurrence occurs commonly following CA due to an inability to deliver lesions of adequate depth to cauterise the electrical circuits that drive VA or reach areas of scar responsible for VA. Stereotactic body radiotherapy is a non-invasive treatment modality that allows volumetric delivery of energy to treat circuits that cannot be reached by CA. It overcomes the weaknesses of CA and has been successfully utilised in small clinical trials to treat refractory VA. This article summarises the current evidence for this novel treatment modality and the steps that will be required to bring it to the forefront of VA treatment.

High PrEP uptake, adherence, persistence and effectiveness outcomes among young Thai men and transgender women who sell sex in Bangkok and Pattaya, Thailand: findings from the open-label combination HIV prevention effectiveness (COPE) study.

Background: Daily oral pre-exposure prophylaxis (PrEP) is effective in preventing HIV infection, but no study has evaluated combination prevention interventions with PrEP for transgender women (TGW) and men who have sex with men (MSM) who sell sex. Methods: The Combination Prevention Effectiveness (COPE) study was a community-based, non-randomized implementation study in Bangkok and Pattaya, Thailand. Participants were HIV-negative MSM and TGW aged 18-26 years who reported exchanging sex with men in the prior 12 months and who met 2014 U.S. Public Health Service PrEP eligibility criteria. The intervention included quarterly HIV testing, semiannual testing for sexually transmitted infections, provision of condoms with lubricant, and the opportunity to initiate or end daily oral PrEP use at any time during study participation. Participants taking PrEP received monthly adherence counseling and short message service reminders. The primary outcome was HIV incidence rate ratio (IRR) on PrEP vs. not on PrEP. Secondary outcomes were PrEP initiation, PrEP use at 12 months, and PrEP adherence. Findings: From October 2017 to August 2019, 846 participants were enrolled: 531 (62.8%) immediately initiated PrEP; 104 (12.3%) subsequently initiated PrEP, and 211 (24.9%) never initiated PrEP. Among those initiating PrEP within 30 days of enrollment; 85.9% were on PrEP at the 12-months. When taking PrEP, participants reported adherent PrEP use at 94.2% of quarterly assessments. Ten HIV seroconversions occurred without PrEP use (incidence rate [IR] = 3.42 per 100 person-years [PY]; 95% CI = 1.64-6.30), while zero cases occurred with PrEP use (IR = 0.0 per 100PY; 95% CI = 0.0-0.62), with IRR = 0.0 (95% CI = 0.0-0.22; p < 0.001). Interpretation: Young Thai MSM and TGW who exchange sex can have high PrEP uptake, persistence and adherence, and low HIV incidence when offered in supportive community-based settings. Funding: U.S. National Institute of Allergy and Infectious Diseases; Centers for Disease Control and Prevention.

Approach to the Physiologically Challenging Endotracheal Intubation in the Intensive Care Unit.

Endotracheal intubation for airway management is a common procedure in the ICU. Intubation may be difficult due to anatomic airway abnormalities but also due to physiologic derangements that predispose patients to cardiovascular collapse during the procedure. Results of studies demonstrate a high incidence of morbidity and mortality associated with airway management in the ICU. To reduce the likelihood of complications, medical teams must be well versed in the general principles of intubation and be prepared to manage physiologic derangements while securing the airway. In this review, we present relevant literature on the approach to endotracheal intubation in the ICU and provide pragmatic recommendations relevant to medical teams performing intubations in patients who are physiologically unstable.

A Critical Discourse Analysis of an Australian Incarcerated Trans Woman's Letters of Complaint and Self-Advocacy.

This case study provides a critical discourse analysis of 121 letters of complaint and self-advocacy authored by Natasha Keating, a trans woman incarcerated in two Australian male correctional facilities from 2000 to 2007. During her incarceration, Natasha experienced victimization, misgendering, microaggression, and institutional discrimination. Despite this, Natasha embodied and "fought" against the injustices she experienced, whilst seeking to speak for other trans incarcerated persons also silenced and treated with indifference, contributing to changes in the carceral system. This original case study analyzes the discursive strategies Natasha employed to construct and reclaim an affirming self-identity through a deliberate campaign to effect social change and policy concessions within a system designed to curtail self-determination. Through her empathic and impassioned letter-writing approach, leveraging a military metaphor, this novel analysis showcases the significant implications her activism/agentism and determination had in naming and seeking to dismantle the systems of oppression trans incarcerated women experience.

HLA-B∗46 associates with rapid HIV disease progression in Asian cohorts and prominent differences in NK cell phenotype.

Human leukocyte antigen (HLA) alleles have been linked to HIV disease progression and attributed to differences in cytotoxic T lymphocyte (CTL) epitope representation. These findings are largely based on treatment-naive individuals of European and African ancestry. We assessed HLA associations with HIV-1 outcomes in 1,318 individuals from Thailand and found HLA-B∗46:01 (B∗46) associated with accelerated disease in three independent cohorts. B∗46 had no detectable effect on HIV-specific T cell responses, but this allele is unusual in containing an HLA-C epitope that binds inhibitory receptors on natural killer (NK) cells. Unbiased transcriptomic screens showed increased NK cell activation in people with HIV, without B∗46, and simultaneous single-cell profiling of surface proteins and transcriptomes revealed a NK cell subset primed for increased responses in the absence of B∗46. These findings support a role for NK cells in HIV pathogenesis, revealed by the unique properties of the B∗46 allele common only in Asia.

Potent monoclonal antibody-mediated neutralization of a divergent Hendra virus variant.

Hendra virus (HeV) and Nipah virus (NiV) are deadly zoonotic Henipaviruses (HNVs) responsible for recurrent outbreaks in humans and domestic species of highly fatal (50 to 95%) disease. A HeV variant (HeV-g2) of unprecedented genetic divergence has been identified in two fatally diseased horses, and in two flying fox species in regions of Australia not previously considered at risk for HeV spillover. Given the HeV-g2 divergence from HeV while retaining equivalent pathogenicity and spillover potential, understanding receptor usage and antigenic properties is urgently required to guide One Health biosecurity. Here, we show that the HeV-g2 G glycoprotein shares a conserved receptor tropism with prototypic HeV and that a panel of monoclonal antibodies recognizing the G and F glycoproteins potently neutralizes HeV-g2­ and HeV G/F­mediated entry into cells. We determined a crystal structure of the Fab fragment of the hAH1.3 antibody bound to the HeV G head domain, revealing an antigenic site associated with potent cross-neutralization of both HeV-g2 and HeV. Structure-guided formulation of a tetravalent monoclonal antibody (mAb) mixture, targeting four distinct G head antigenic sites, results in potent neutralization of HeV and HeV-g2 and delineates a path forward for implementing multivalent mAb combinations for postexposure treatment of HNV infections.

Transactional sex, HIV and health among young cisgender men and transgender women who have sex with men in Thailand.

PURPOSE: To examine how recent sex work is identified and the HIV risk factors and service needs among Thai cisgender men who have sex with men (MSM) and transgender women (TGW) who exchange sex. METHODS: MSM and TGW in Bangkok and Pattaya who exchanged sex in the last year (n = 890) were recruited through social media, outreach, and word-of-mouth. Recent sex exchange was based on the primary question, "In the last 30 days, have you sold or traded sex"; secondary questions (regarding income source and client encounters) were also investigated. RESULTS: Overall, 436 (48%) participants engaged in sex work in the last 30 days; among those, 270 (62%) reported exchanging sex by the primary question, and 160 (37%) based on secondary questions only. Recent sex exchange was associated with gonorrhea, syphilis, discussing PrEP with others, and using condoms, alcohol, methamphetamine, amyl nitrate, and Viagra. Exchanging sex based on secondary questions only was associated with being in a relationship, social media recruitment, less recent anal intercourse, and not discussing PrEP. CONCLUSIONS: Thai MSM and TGW who exchange sex need regular access to HIV/STI prevention, testing, and treatment services, and multiple approaches to assessing sex work will help identify and serve this diverse and dynamic population.

Diverse contexts and social factors among young cisgender men and transgender women who sell or trade sex in Bangkok and Pattaya, Thailand: formative research for a PrEP program implementation study.

HIV incidence is high and persistent among cisgender men who have sex with men (MSM) and transgender women (TGW) who have sex with men, particularly among those who sell or trade sex. In preparation for an open-label combination HIV pre-exposure prophylaxis (PrEP) program for these groups, we conducted formative research to explore the context of sex work/trade and factors that affect implementation of PrEP interventions. This study analyzed interviews with 20 young (aged 18-26 years) MSM and TGW who sell/trade sex and three sex work venue managers in Bangkok and Pattaya, Thailand. Participants described diverse contexts of sex work/trade, including in multiple informal and formal sex venues. Several participants reported mobility across provinces and out of the country, which led to intermittent sex work/trade. TGW sex workers reported challenges with access and cost of femininizing hormones and limited employment opportunities. Factors that could facilitate or challenge PrEP program implementation included HIV stigma, the role of venue management in sexual health practice, lack of PrEP knowledge, lower perceived HIV risk, and interest in personal health and wellbeing. Program implementers must consider myriad factors to successfully implement PrEP among young MSM and TGW engaged in sex work or trade in Thailand.

Architecture and antigenicity of the Nipah virus attachment glycoprotein.

Nipah virus (NiV) and Hendra virus (HeV) are zoonotic henipaviruses (HNVs) responsible for outbreaks of encephalitis and respiratory illness. The entry of HNVs into host cells requires the attachment (G) and fusion (F) glycoproteins, which are the main targets of antibody responses. To understand viral infection and host immunity, we determined a cryo-electron microscopy structure of the NiV G homotetrameric ectodomain in complex with the nAH1.3 broadly neutralizing antibody Fab fragment. We show that a cocktail of two nonoverlapping G-specific antibodies neutralizes NiV and HeV synergistically and limits the emergence of escape mutants. Analysis of polyclonal serum antibody responses elicited by vaccination of macaques with NiV G indicates that the receptor binding head domain is immunodominant. These results pave the way for implementing multipronged therapeutic strategies against these deadly pathogens.

Evaluation of screening strategies for pulmonary tuberculosis among hospitalized patients in a low-burden setting: cost-effectiveness of GeneXpert MTB/RIF compared to smear microscopy.

OBJECTIVE: Hospitalized patients undergoing evaluation for pulmonary tuberculosis (TB) require airborne isolation while testing for Mycobacterium tuberculosis (MTB) to reduce risk of nosocomial transmission. GeneXpert MTB/RIF (Xpert) is more rapid and accurate than sputum smear microscopy, but it is not routinely used to 'rule out' infectious pulmonary TB among hospitalized patients in the United States. We sought to evaluate the diagnostic performance and cost-effectiveness of Xpert-based TB evaluation. METHODS: We conducted a retrospective cohort study of hospitalized adults evaluated for pulmonary TB at a large academic medical center in New York from 2010 to 2017. Using propensity score matching, we compared hospital length-of-stay among patients undergoing conventional smear-based TB evaluation to a control group with non-TB pneumonia. We performed a probabilistic cost-effectiveness analysis to compare Xpert-based versus conventional TB evaluation. RESULTS: In total 1,421 patients were evaluated for TB with airborne isolation and sputum testing; mycobacterial culture was positive for MTB in 49 (3.4%). Conventional TB evaluation was associated with an increase of 4.4 hospital days compared to propensity-matched controls. Xpert-based testing strategies dominated conventional TB evaluation with a cost savings of $5,947 (95% CI, $1,156-$12,540) and $4,445 (95% CI, $696-$9,526) per patient depending on the number of Xpert tests performed (1 vs 2, respectively) and assumptions about the reduction of length of stay achieved. CONCLUSIONS: In the evaluation of hospitalized patients for pulmonary TB, Xpert-based testing has superior diagnostic performance and is likely cost-effective compared to smear microscopy due to reduced hospital length-of-stay associated with more rapid test results.

HIV and syphilis prevalence among transgender women and men who have sex with men, Silom Community Clinic, Bangkok, Thailand, 2017-2019.

We assessed HIV and syphilis infection among MSM and TGW attending Silom Community Clinic from 2017 to 2019. Walk-in and referral clients completed a registration application including a question on gender identity. We compared the prevalence of HIV, syphilis, and HIV and syphilis coinfection among TGW and MSM. In a total of 1050 clients, 276 (26.3%) were TGW and 774 (74.7%) were MSM. Among TGW clients, HIV prevalence was 29.8%, syphilis prevalence was 38.4%, and coinfection prevalence was 18.5%. Comparing prevalence among TGW to MSM, the adjusted prevalence ratio (aPR) for HIV was 1.8 (95% CI:1.4-2.3), for syphilis was 1.2 (95% CI:1.0-1.4), and for HIV and syphilis coinfection was 2.1 (95% CI:1.4-2.9). The prevalence of syphilis was higher than HIV among TGW, with a PR of 1.3 (95% CI:1.1-1.6), and among MSM, with a PR of 1.4 (95% CI:1.2-1.7). TGW age 15-21 years had an HIV prevalence of 16.9% and syphilis prevalence of 30.8%. After adjusting for age, referral, and sexual behaviors, TGW remain significantly associated with HIV and syphilis prevalence. There is a substantial burden of HIV and HIV/syphilis co-infection among TGW. HIV/STI prevention are needed for TGW, including linkage to HIV care.

Epidemiology of anal human papillomavirus infection and high-grade squamous intraepithelial lesions in 29 900 men according to HIV status, sexuality, and age: a collaborative pooled analysis of 64 studies.

BACKGROUND: Robust age-specific estimates of anal human papillomavirus (HPV) and high-grade squamous intraepithelial lesions (HSIL) in men can inform anal cancer prevention efforts. We aimed to evaluate the age-specific prevalence of anal HPV, HSIL, and their combination, in men, stratified by HIV status and sexuality. METHODS: We did a systematic review for studies on anal HPV infection in men and a pooled analysis of individual-level data from eligible studies across four groups: HIV-positive men who have sex with men (MSM), HIV-negative MSM, HIV-positive men who have sex with women (MSW), and HIV-negative MSW. Studies were required to inform on type-specific HPV infection (at least HPV16), detected by use of a PCR-based test from anal swabs, HIV status, sexuality (MSM, including those who have sex with men only or also with women, or MSW), and age. Authors of eligible studies with a sample size of 200 participants or more were invited to share deidentified individual-level data on the above four variables. Authors of studies including 40 or more HIV-positive MSW or 40 or more men from Africa (irrespective of HIV status and sexuality) were also invited to share these data. Pooled estimates of anal high-risk HPV (HR-HPV, including HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68), and HSIL or worse (HSIL+), were compared by use of adjusted prevalence ratios (aPRs) from generalised linear models. FINDINGS: The systematic review identified 93 eligible studies, of which 64 contributed data on 29 900 men to the pooled analysis. Among HIV-negative MSW anal HPV16 prevalence was 1·8% (91 of 5190) and HR-HPV prevalence was 6·9% (345 of 5003); among HIV-positive MSW the prevalences were 8·7% (59 of 682) and 26·9% (179 of 666); among HIV-negative MSM they were 13·7% (1455 of 10 617) and 41·2% (3798 of 9215), and among HIV-positive MSM 28·5% (3819 of 13 411) and 74·3% (8765 of 11 803). In HIV-positive MSM, HPV16 prevalence was 5·6% (two of 36) among those age 15-18 years and 28·8% (141 of 490) among those age 23-24 years (ptrend=0·0091); prevalence was 31·7% (1057 of 3337) among those age 25-34 years and 22·8% (451 of 1979) among those age 55 and older (ptrend<0·0001). HPV16 prevalence in HIV-negative MSM was 6·7% (15 of 223) among those age 15-18 and 13·9% (166 of 1192) among those age 23-24 years (ptrend=0·0076); the prevalence plateaued thereafter (ptrend=0·72). Similar age-specific patterns were observed for HR-HPV. No significant differences for HPV16 or HR-HPV were found by age for either HIV-positive or HIV-negative MSW. HSIL+ detection ranged from 7·5% (12 of 160) to 54·5% (61 of 112) in HIV-positive MSM; after adjustment for heterogeneity, HIV was a significant predictor of HSIL+ (aPR 1·54, 95% CI 1·36-1·73), HPV16-positive HSIL+ (1·66, 1·36-2·03), and HSIL+ in HPV16-positive MSM (1·19, 1·04-1·37). Among HPV16-positive MSM, HSIL+ prevalence increased with age. INTERPRETATION: High anal HPV prevalence among young HIV-positive and HIV-negative MSM highlights the benefits of gender-neutral HPV vaccination before sexual activity over catch-up vaccination. HIV-positive MSM are a priority for anal cancer screening research and initiatives targeting HPV16-positive HSIL+. FUNDING: International Agency for Research on Cancer.

Study protocol of the LARK (TROG 17.03) clinical trial: a phase II trial investigating the dosimetric impact of Liver Ablative Radiotherapy using Kilovoltage intrafraction monitoring.

BACKGROUND: Stereotactic Ablative Body Radiotherapy (SABR) is a non-invasive treatment which allows delivery of an ablative radiation dose with high accuracy and precision. SABR is an established treatment for both primary and secondary liver malignancies, and technological advances have improved its efficacy and safety. Respiratory motion management to reduce tumour motion and image guidance to achieve targeting accuracy are crucial elements of liver SABR. This phase II multi-institutional TROG 17.03 study, Liver Ablative Radiotherapy using Kilovoltage intrafraction monitoring (LARK), aims to investigate and assess the dosimetric impact of the KIM real-time image guidance technology. KIM utilises standard linear accelerator equipment and therefore has the potential to be a widely available real-time image guidance technology for liver SABR. METHODS: Forty-six patients with either hepatocellular carcinoma or oligometastatic disease to the liver suitable for and treated with SABR using Kilovoltage Intrafraction Monitoring (KIM) guidance will be included in the study. The dosimetric impact will be assessed by quantifying accumulated patient dose distribution with or without the KIM intervention. The patient treatment outcomes of local control, toxicity and quality of life will be measured. DISCUSSION: Liver SABR is a highly effective treatment, but precise dose delivery is challenging due to organ motion. Currently, there is a lack of widely available options for performing real-time tumour localisation to assist with accurate delivery of liver SABR. This study will provide an assessment of the impact of KIM as a potential solution for real-time image guidance in liver SABR. TRIAL REGISTRATION: This trial was registered on December 7th 2016 on ClinicalTrials.gov under the trial-ID NCT02984566 .

Neisseria Meningitidis Urethritis in a Thai Male.

Although Neisseria meningitidis (N. meningitidis) urogenital infections have been reported widely, meningococcal urethritis has not been reported previously in Thailand. A 42-year-old Thai male presented at a sexual health clinic with dysuria and urethral discharge following oral and insertive anal intercourse. N. meningitidis, serogroup C was cultured from a urethral discharge specimen and the patient was treated successfully with standard treatment for gonococcal urethritis. This case reflects a growing trend of reports describing meningococcal urethritis, likely resulting from sexual contact.

Antiretroviral treatment initiation among HIV-positive participants in the Bangkok men who have sex with men cohort study, 2006-2016.

INTRODUCTION: Data on HIV antiretroviral therapy (ART) initiation among key-affected populations will support reaching the UNAIDS goal to end AIDS by 2030. METHODS: We assessed ART initiation among HIV-positive participants of the Bangkok Men Who Have Sex with Men (MSM) Cohort Study, which enrolled sexually experienced MSM aged ≥ 18 years and included visits every four months for a period of 3-5 years, from 2006-2016. At each visit, participants had HIV testing and completed computer-assisted self-interviewing on demographics and HIV risk behaviors. If they acquired HIV infection during the study, they received active referral for HIV treatment, continued in the cohort, and were asked about ART initiation. We used logistic regression to determine factors associated with ART initiation. RESULTS: Overall, 632 (36.2%) participants were diagnosed with HIV infection; 463 (73%) had a follow-up visit reporting information about ART, of those 346 (74%) reported ART initiation, with 323 (93%) on ART initiating ART through their registered national health benefit program. Only 70 (11%) were eligible for ART at time of diagnosis, and 52 (74%) initiated ART, on average, within six months of diagnosis. Multivariable analysis evaluating factors associated with ART initiation demonstrated that low CD4 cell count at time of diagnosis was the only independent factor associated with ART initiation. CONCLUSIONS: Most HIV-positive participants in the cohort reported ART initiation through the national health benefit program but limited data suggests there could be improvements in length of time to initiation of ART. Efforts should focus on ART start in MSM and transgender women soon after HIV diagnosis.

Altered Antibody Responses in Persons Infected with HIV-1 While Using Preexposure Prophylaxis.

Preexposure prophylaxis (PrEP) is an effective HIV prevention tool, although effectiveness is dependent upon adherence. It is important to characterize the impact of PrEP on HIV antibody responses in people who experience breakthrough infections to understand the potential impact on timely diagnosis and treatment. Longitudinal HIV-1-specific antibody responses were evaluated in 42 people who inject drugs (PWID) from the Bangkok Tenofovir Study (BTS) (placebo = 28; PrEP = 14) who acquired HIV while receiving PrEP. HIV-1 antibody levels and avidity to three envelope proteins (gp41, gp160, and gp120) were measured in the plasma using a customized Bio-Plex (Bio-Rad Laboratories, Hercules, CA) assay. A time-to-event analysis was performed for each biomarker to compare the distribution of times at which study subjects exceeded the recent/long-term assay threshold, comparing PrEP and placebo treatment groups. We fit mixed-effects models to identify longitudinal differences in antibody levels and avidity between groups. Overall, longitudinal antibody levels and avidity were notably lower in the PrEP breakthrough group compared to the placebo group. Time-to-event analyses demonstrated a difference in time to antibody reactivity between treatment groups for all Bio-Plex biomarkers. Longitudinal gp120 antibody levels within the PrEP breakthrough group were decreased compared to the placebo group. When accounting for PrEP adherence, both gp120 and gp160 antibody levels were lower in the PrEP breakthrough group compared to the placebo group. We demonstrate hindered envelope antibody maturation in PWID who became infected while receiving PrEP in the BTS, which has significant implications for HIV diagnosis. Delayed maturation of the antibody response to HIV may increase the time to detection for antibody-based tests. Clinical Trial Registration Number, NCT00119106.

Recent declines in HIV infections at Silom Community Clinic Bangkok, Thailand corresponding to HIV prevention scale up: An open cohort assessment 2005-2018.

OBJECTIVES: We assessed HIV-1 infection among men who have sex with men (MSM) attending Silom Community Clinic (SCC) in Bangkok, Thailand from 2005 to 2018. Since 2014, Thailand increased implementation of HIV prevention strategies including pre-exposure prophylaxis and Treatment as Prevention. METHODS: MSM attending SCC were tested for HIV using rapid tests. We assessed trends in HIV prevalence, incidence and compared incidence before and after 2014. RESULTS: From 2005 to 2018, 14,034 clients attended SCC for HIV testing. The HIV prevalence increased from 19.2% in 2005-2006 to 34-0% in 2010, remained stable until 2016 and decreased to 17.2% in 2018 (p<0.0001). The HIV incidence was 4.1 per 100 person-years (PY), with an inverted U-shape trend and a peak in 2009 (p<0.0001). Incidence among young MSM aged 13-21 years remained high at 10.0 per 100 PY. Among those aged 22-29 years, lower incidence was found from Q 3 2016, with a relative risk reduction of 46.2% (p<0.001); and a similar reduction among those aged ≥30 years from Q4 2014, corresponding to scale up of HIV prevention strategies. CONCLUSION: We found a decline in HIV infection among Thai MSM. However, incidence remained high among young MSM.

Complete Genome Sequences of Three Neisseria gonorrhoeae Isolates from Thailand with Multidrug Resistance and Multilocus Sequence Type 1903.

Multilocus sequence typing (MLST) sequence type 1903 (ST1903) is the most common ST of ceftriaxone-resistant Neisseria gonorrhoeae Here, we report three completed genome sequences of MLST ST1903 N. gonorrhoeae isolates collected from patients at Faculty of Medicine Siriraj Hospital, a university hospital in Bangkok, Thailand, in 2009 to 2011.

Testing the Effectiveness and Cost-Effectiveness of a Combination HIV Prevention Intervention Among Young Cisgender Men Who Have Sex With Men and Transgender Women Who Sell or Exchange Sex in Thailand: Protocol for the Combination Prevention Effectiveness Study.

BACKGROUND: Pre-exposure prophylaxis (PrEP) is highly effective in the prevention of HIV acquisition, particularly for men who have sex with men (MSM). Questions remain on the benefits of PrEP and implementation strategies for those at occupational risk of HIV acquisition in sex work, as well as on methods to support adherence among young people who initiate PrEP. OBJECTIVE: The Combination Prevention Effectiveness study for young cisgender MSM and transgender women (TGW) aims to assess the effectiveness and cost-effectiveness of a combination intervention among HIV-uninfected young MSM and TGW engaged in sex work in Thailand. METHODS: This open-label, nonrandomized assessment compares the relative effectiveness of a combination prevention intervention with and without daily oral emtricitabine and tenofovir disoproxil fumarate (Truvada) PrEP with SMS-based adherence support. HIV-uninfected young MSM and TGW aged 18 to 26 years in Bangkok and Pattaya who self-report selling/exchanging sex at least once in the previous 12 months are recruited by convenience sampling and peer referral and are eligible regardless of their intent to initiate PrEP. At baseline, participants complete a standard assessment for PrEP eligibility and may initiate PrEP then or at any time during study participation. All participants complete a survey and HIV testing at baseline and every 3 months. Participants who initiate PrEP complete monthly pill pickups and may opt-in to SMS reminders. All participants are sent brief weekly SMS surveys to assess behavior with additional adherence questions for those who initiated PrEP. Adherence is defined as use of 4 or more pills within the last 7 days. The analytic plan uses a person-time approach to assess HIV incidence, comparing participant time on oral PrEP to participant time off oral PrEP for 12 to 24 months of follow-up, using a propensity score to control for confounders. Enrollment is based on the goal of observing 620 person-years (PY) on PrEP and 620 PY off PrEP. RESULTS: As of February 2019, 445 participants (417 MSM and 28 TGW) have contributed approximately 168 PY with 95% (73/77) retention at 12 months. 74.2% (330/445) of enrolled participants initiated PrEP at baseline, contributing to 134 PY of PrEP adherence, 1 PY nonadherence, and 33 PY PrEP nonuse/noninitiation. Some social harms, predominantly related to unintentional participant disclosure of PrEP use and peer stigmatization of PrEP and HIV, have been identified. CONCLUSIONS: The majority of cisgender MSM and TGW who exchange sex and participate in this study are interested in PrEP, report taking sufficient PrEP, and stay on PrEP, though additional efforts are needed to address community misinformation and stigma. This novel multilevel, open-label study design and person-time approach will allow evaluation of the effectiveness and cost-effectiveness of combination prevention intervention in the contexts of both organized sex work and exchanged sex. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/15354.

Persistence of Ebola virus after the end of widespread transmission in Liberia: an outbreak report.

BACKGROUND: Outbreak response efforts for the 2014-15 Ebola virus disease epidemic in west Africa brought widespread transmission to an end. However, subsequent clusters of infection have occurred in the region. An Ebola virus disease cluster in Liberia in November, 2015, that was identified after a 15-year-old boy tested positive for Ebola virus infection in Monrovia, raised the possibility of transmission from a persistently infected individual. METHODS: Case investigations were done to ascertain previous contact with cases of Ebola virus disease or infection with Ebola virus. Molecular investigations on blood samples explored a potential linkage between Ebola virus isolated from cases in this November, 2015, cluster and epidemiologically linked cases from the 2014-15 west African outbreak, according to the national case database. FINDINGS: The cluster investigated was the family of the index case (mother, father, three siblings). Ebola virus genomes assembled from two cases in the November, 2015, cluster, and an epidemiologically linked Ebola virus disease case in July, 2014, were phylogenetically related within the LB5 sublineage that circulated in Liberia starting around August, 2014. Partial genomes from two additional individuals, one from each cluster, were also consistent with placement in the LB5 sublineage. Sequencing data indicate infection with a lineage of the virus from a former transmission chain in the country. Based on serology and epidemiological and genomic data, the most plausible scenario is that a female case in the November, 2015, cluster survived Ebola virus disease in 2014, had viral persistence or recurrent disease, and transmitted the virus to three family members a year later. INTERPRETATION: Investigation of the source of infection for the November, 2015, cluster provides evidence of Ebola virus persistence and highlights the risk for outbreaks after interruption of active transmission. These findings underscore the need for focused prevention efforts among survivors and sustained capacity to rapidly detect and respond to new Ebola virus disease cases to prevent recurrence of a widespread outbreak. FUNDING: US Centers for Disease Control and Prevention, Defense Threat Reduction Agency, and WHO.