Tracking coreceptor switch of the transmitted/founder HIV-1 identifies co-evolution of HIV-1 antigenicity, coreceptor usage and CD4 subset targeting: the RV217 acute infection cohort study.

BACKGROUND: The CCR5 (R5) to CXCR4 (X4) coreceptor switch in natural HIV-1 infection is associated with faster progression to AIDS, but the mechanisms remain unclear. The difficulty in elucidating the evolutionary origin of the earliest X4 viruses limits our understanding of this phenomenon. METHODS: We tracked the evolution of the transmitted/founder (T/F) HIV-1 in RV217 participants identified in acute infection. The origin of the X4 viruses was elucidated by single genome amplification, deep sequencing and coreceptor assay. Mutations responsible for coreceptor switch were confirmed by mutagenesis. Viral susceptibility to neutralization was determined by neutralization assay. Virus CD4 subset preference was demonstrated by sequencing HIV-1 RNA in sorted CD4 subsets. FINDINGS: We demonstrated that the earliest X4 viruses evolved de novo from the T/F strains. Strong X4 usage can be conferred by a single mutation. The mutations responsible for coreceptor switch can confer escape to neutralization and drive the X4 variants to replicate mainly in the central memory (CM) and naïve CD4 subsets. Likely due to the smaller viral burst size of the CM and naïve subsets, the X4 variants existed at low frequency in plasma. The origin of the X4 viruses preceded accelerated CD4 decline. All except one X4 virus identified in the current study lost the conserved V3 N301 glycan site. INTERPRETATIONS: The findings demonstrate co-evolution of HIV-1 antigenicity, coreceptor usage and CD4 subset targeting which have implications for HIV-1 therapeutics and functional cure. The observations provide evidence that coreceptor switch can function as an evolutionary mechanism of immune evasion. FUNDING: Institute of Human Virology, National Institutes of Health, Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc, Thai Red Cross AIDS Research Centre, Gilead Sciences, Merck, and ViiV Healthcare.

Transmission of highly virulent CXCR4 tropic HIV-1 through the mucosal route in an individual with a wild-type CCR5 genotype.

Nearly all transmitted/founder (T/F) HIV-1 are CCR5 (R5)-tropic. While previous evidence suggested that CXCR4 (X4)-tropic HIV-1 are transmissible, detection was not at the earliest stages of acute infection. Here, we identified an X4-tropic T/F HIV-1 in a participant in acute infection cohort. Coreceptor assays demonstrated that this T/F virus is strictly CXCR4 tropic. The participant experienced significantly faster CD4 depletion compared with R5 virus infected participants in the same cohort. Naïve and central memory CD4 subsets declined faster than effector and transitional memory subsets. All CD4 subsets, including naïve, were productively infected. Increased CD4+ T cell activation was observed over time. This X4-tropic T/F virus is resistant to broadly neutralizing antibodies (bNAbs) targeting V1/V2 and V3 regions. These findings demonstrate that X4-tropic HIV-1 is transmissible through the mucosal route in people with the wild-type CCR5 genotype and have implications for understanding the transmissibility and immunopathogenesis of X4-tropic HIV-1.

Transmission of highly virulent CXCR4 tropic HIV-1 through the mucosal route in an individual with a wild-type CCR5 genotype.

Nearly all transmitted/founder (T/F) HIV-1 are CCR5 (R5)-tropic. While previous evidence suggested that CXCR4 (X4)-tropic HIV-1 are transmissible, detection was not at the earliest stages of acute infection. Here, we identified an X4-tropic T/F HIV-1 in a participant in acute infection cohort. Coreceptor assays demonstrated that this T/F virus is strictly CXCR4 tropic. The participant experienced significantly faster CD4 depletion compared with R5 virus infected participants in the same cohort. Naïve and central memory CD4 subsets declined faster than effector and transitional memory subsets. All CD4 subsets, including naïve, were productively infected. Increased CD4 + T cell activation was observed over time. This X4-tropic T/F virus is resistant to broadly neutralizing antibodies (bNAbs) targeting V1/V2 and V3 regions. These findings demonstrate that X4-tropic HIV-1 is transmissible through the mucosal route in people with the wild-type CCR5 genotype and have implications for understanding the transmissibility and immunopathogenesis of X4-tropic HIV-1.

Unique HIV Risk Factors and Prevention Needs for Transgender Women and Cisgender Men Who Have Sex with Men in Bangkok, Thailand.

Background: Transgender women (TGW) and cisgender men who have sex with men (cis-MSM) are often grouped together as key populations. We evaluated behavioral and other characteristics that may distinguish TGW from cis-MSM in Bangkok, Thailand. Methods: We enrolled into an 18-month cohort cis-MSM and TGW 18-35 years of age without HIV, who reported anal intercourse plus condomless anal intercourse, multiple partners, transactional sex, and/or sexually transmitted infection. Robust multivariable Poisson regression was used to estimate adjusted prevalence ratios (aPRs) and confidence intervals (95% CIs) for associations with being a TGW. Among TGW, logistic regression with generalized estimating equations was used to estimate adjusted odds ratios (aORs) and 95% CIs for associations with taking hormones and having undergone gender affirmation surgery (GAS). Results: From 2017 to 2019, 660 cis-MSM and 348 TGW were enrolled. Compared to cis-MSM, TGW were more likely to be attracted to mostly/only men (aPR: 3.79, 95% CI: 1.57-9.13), have a higher monthly income (aPR: 1.25, 95% CI: 1.04-1.50), have lived in their current residence for <1 year (aPR: 1.21, 95% CI: 1.01-1.46), have engaged in sex work (aPR: 1.48, 95% CI: 1.23-1.77), and be less likely to have ever undergone HIV testing (aPR: 0.83, 95% CI: 0.70-0.98). Among TGW, 149 (42.8%) were taking hormones and 33 (9.5%) had undergone GAS. GAS was more common among TGW who ever used methamphetamines (aOR: 1.55, 95% CI: 1.00-2.41) and those >23 years (18-20-year olds aOR: 0.17, 95% CI: 0.05-0.55; 21-23-year olds aOR: 0.36, 95% CI: 0.20-0.65). Conclusions: TGW and cis-MSM are unique populations; tailored, gender-affirming, differentiated models of HIV prevention and care are necessary to address vulnerabilities specific to each key population.

Achieving the third 95 in sub-Saharan Africa: application of machine learning approaches to predict viral failure.

OBJECTIVE: Viral failure in people with HIV (PWH) may be influenced by multiple sociobehavioral, clinical, and context-specific factors, and supervised learning approaches may identify novel predictors. We compared the performance of two supervised learning algorithms to predict viral failure in four African countries. DESIGN: Cohort study. METHODS: The African Cohort Study is an ongoing, longitudinal cohort enrolling PWH at 12 sites in Uganda, Kenya, Tanzania, and Nigeria. Participants underwent physical examination, medical history-taking, medical record extraction, sociobehavioral interviews, and laboratory testing. In cross-sectional analyses of enrollment data, viral failure was defined as a viral load at least 1000 copies/ml among participants on antiretroviral therapy (ART) for at least 6 months. We compared the performance of lasso-type regularized regression and random forests by calculating area under the curve (AUC) and used each to identify factors associated with viral failure; 94 explanatory variables were considered. RESULTS: Between January 2013 and December 2020, 2941 PWH were enrolled, 1602 had been on antiretroviral therapy (ART) for at least 6 months, and 1571 participants with complete case data were included. At enrollment, 190 (12.0%) had viral failure. The lasso regression model was slightly superior to the random forest in its ability to identify PWH with viral failure (AUC: 0.82 vs. 0.75). Both models identified CD4 + count, ART regimen, age, self-reported ART adherence and duration on ART as important factors associated with viral failure. CONCLUSION: These findings corroborate existing literature primarily based on hypothesis-testing statistical approaches and help to generate questions for future investigations that may impact viral failure.

Human interactions with bats and bat coronaviruses in rural Côte d'Ivoire.

Bats are presumed reservoirs of diverse α- and ß- coronaviruses (CoVs) and understanding the diversity of bat-CoVs and the role bats play in CoV transmission is highly relevant in the context of the current COVID pandemic. We sampled bats in Côte d'Ivoire (2016-2018) living at ecotones between anthropogenic and wild habitats in the Marahoué National Park, a recently encroached protected area, to detect and characterize the CoVs circulating in bats and humans. A total of 314 bats were captured, mostly during the rainy season (78%), and CoV RNA was detected in three of the bats (0.96%). A CoV RNA sequence similar to Chaerephon bat coronavirus/Kenya/KY22/2006 (BtKY22) was found in a Chaerephon cf. pumilus and a Mops sp. fecal swab, while a CoV RNA sequence similar to the two almost identical Kenya bat coronaviruses BtKY55 and BtKY56 (BtKY55/56) was detected in an Epomops buettikoferi oral swab. Phylogenetic analyses indicated differences in the degree of evolutionary host-virus co-speciation for BtKY22 and BtKY55/56. To assess potential for human exposure to these viruses, we conducted human syndromic and community-based surveillance in clinics and high-risk communities. We collected data on participant characteristics, livelihoods, animal contact, and high-risk behaviors that may be associated with exposure to zoonotic diseases. We then collected biological samples for viral testing from 401 people. PCR testing of these biological samples revealed no evidence of CoV infection among the enrolled individuals. We identified higher levels of exposure to bats in people working in crop production and in hunting, trapping and fishing. Finally, we used the 'Spillover' risk-ranking tool to assess the potential for viral spillover and concluded that, while there is no evidence to suggest imminent risk of spillover for these CoVs, their host range and other traits suggest caution and vigilance are warranted in people with high exposure risk.

Assessing Behavioral Risk Factors Driving Zoonotic Spillover Among High-risk Populations in Myanmar.

The increasing global emergence of zoonoses warrants improved awareness of activities that predispose vulnerable communities to greater risk of disease. Zoonotic disease outbreaks regularly occur within Myanmar and at its borders partly due to insufficient knowledge of behavioral risks, hindering participatory surveillance and reporting. This study employed a behavioral surveillance strategy among high-risk populations to understand the behavioral risks for zoonotic disease transmission in an effort to identify risk factors for pathogen spillover. To explore behavioral mechanisms of spillover in Myanmar, we aimed to: (1) evaluate the details around animal contact and types of interaction, (2) assess the association between self-reported unusual symptoms (i.e., any illness or sickness that is not known or recognized in the community or diagnosed by medical providers) and animal contact activities and (3) identify the potential risk factors including behavioral practices of self-reported illness. Participants were enrolled at two community sites: Hpa-An and Hmawbi in Southern Myanmar. A behavioral questionnaire was administered to understand participants' animal exposures, behaviors and self-reported illnesses. From these responses, associations between (1) animal contact activities and self-reported unusual illnesses, and (2) potential risk factors and self-reported unusual illness were tested. Contact with poultry seemed to be very frequent (91.1%) and many participants reported raising, handling and having poultry in their houses as well as slaughtering or being scratched/bitten by them, followed by contact with rodents (57.8%) and swine (17.9%). Compared to participants who did not have any unusual symptoms, participants who had unusual symptoms in the past year were more likely to have sold dead animals (OR = 13.6, 95% CI 6.8-27.2), slaughtered (OR = 2.4, 95% CI 1.7-3.3), raised (OR = 3.4, 95% CI 2.3-5.0) or handled animals (OR = 2.1, 95% CI 1.2-3.6), and had eaten sick (OR = 4.4, 95% CI 3.0-6.4) and/or dead animals (OR = 6.0, 95% CI 4.1-8.8) in the same year. Odds of having reported unusual symptoms was higher among those involved in animal production business (OR = 3.4, 95% CI 1.9-6.2) and animal-involved livelihoods (OR = 3.3, 95% CI 1.5-7.2) compared to other livelihoods. The results suggest that there is a high level of interaction between humans, livestock and wild animals in communities we investigated in Myanmar. The study highlights the specific high-risk behaviors as they relate to animal contact and demographic risk factors for zoonotic spillover. Our findings contribute to human behavioral data needed to develop targeted interventions to prevent zoonotic disease transmission at human-animal interfaces.

Tracking coreceptor switch of the transmitted/founder HIV-1 identifies co-evolution of HIV-1 antigenicity, coreceptor usage and CD4 subset targeting.

The CCR5 (R5) to CXCR4 (X4) coreceptor switch in natural HIV-1 infection is associated with faster progression to AIDS, but the underlying mechanisms remain unclear. The difficulty in capturing the earliest moment of coreceptor switch in vivo limits our understanding of this phenomenon. Here, by tracking the evolution of the transmitted/founder (T/F) HIV-1 in a prospective cohort of individuals at risk for HIV-1 infection identified very early in acute infection, we investigated this process with high resolution. The earliest X4 variants evolved from the R5 tropic T/F strains. Strong X4 usage can be conferred by a single mutation. The mutations responsible for coreceptor switch can confer escape to neutralization and drive X4 variants to replicate mainly in the central memory and naïve CD4+ T cells. We propose a novel concept to explain the co-evolution of virus antigenicity and entry tropism termed "escape by shifting". This concept posits that for viruses with receptor or coreceptor flexibility, entry tropism alteration represents a mechanism of immune evasion in vivo .

Coronavirus Antibody Responses before COVID-19 Pandemic, Africa and Thailand.

Prior immune responses to coronaviruses might affect human SARS-CoV-2 response. We screened 2,565 serum and plasma samples collected from 2013 through early 2020, before the COVID-19 pandemic began, from 2,250 persons in 4 countries in Africa (Kenya, Nigeria, Tanzania, and Uganda) and in Thailand, including persons living with HIV-1. We detected IgG responses to SARS-CoV-2 spike (S) subunit 2 protein in 1.8% of participants. Profiling against 23 coronavirus antigens revealed that responses to S, subunit 2, or subunit 1 proteins were significantly more frequent than responses to the receptor-binding domain, S-Trimer, or nucleocapsid proteins (p<0.0001). We observed similar responses in persons with or without HIV-1. Among all coronavirus antigens tested, SARS-CoV-2, SARS-CoV-1, and Middle East respiratory syndrome coronavirus antibody responses were much higher in participants from Africa than in participants from Thailand (p<0.01). We noted less pronounced differences for endemic coronaviruses. Serosurveys could affect vaccine and monoclonal antibody distribution across global populations.

Acute HIV-1 infection viremia associate with rebound upon treatment interruption.

BACKGROUND: Analytic treatment interruption (ATI) studies evaluate strategies to potentially induce remission in people living with HIV-1 but are often limited in sample size. We combined data from four studies that tested three interventions (vorinostat/hydroxychloroquine/maraviroc before ATI, Ad26/MVA vaccination before ATI, and VRC01 antibody infusion during ATI). METHODS: The statistical validity of combining data from these participants was evaluated. Eleven variables, including HIV-1 viral load at diagnosis, Fiebig stage, and CD4+ T cell count were evaluated using pairwise correlations, statistical tests, and Cox survival models. FINDINGS: Participants had homogeneous demographic and clinical characteristics. Because an antiviral effect was seen in participants who received VRC01 infusion post-ATI, these participants were excluded from the analysis, permitting a pooled analysis of 53 participants. Time to viral rebound was significantly associated with variables measured at the beginning of infection: pre-antiretroviral therapy (ART) viral load (HR = 1.34, p = 0.022), time to viral suppression post-ART initiation (HR = 1.07, p < 0.001), and area under the viral load curve (HR = 1.34, p = 0.026). CONCLUSIONS: We show that higher viral loads in acute HIV-1 infection were associated with faster viral rebound, demonstrating that the initial stage of HIV-1 infection before ART initiation has a strong impact on viral rebound post-ATI years later. FUNDING: This work was supported by a cooperative agreement between the Henry M. Jackson Foundation for the Advancement of Military Medicine and the US Department of the Army (W81XWH-18-2-0040). This research was funded, in part, by the US National Institute of Allergy and Infectious Diseases (AAI20052001) and the I4C Martin Delaney Collaboratory (5UM1AI126603-05).

Factors associated with testing for HIV and other sexually transmitted infections in men who have sex with men and transgender women in Bangkok, Thailand.

BACKGROUND: Routine screening for HIV and other sexually transmitted infections (STIs) facilitates early diagnosis and treatment, thereby preventing morbidity and onward transmission. We estimated the prevalence of prior HIV/STI testing among men who have sex with men (MSM) and transgender women (TGW) in Bangkok, Thailand, and identified factors associated with prior testing. METHODS: Cross-sectional analyses were performed using data collected at enrollment into an HIV incidence cohort. From April to October 2017, MSM and TGW were enrolled if they were aged 18-35 years, reported anal intercourse with a male or TGW partner, and reported behavioral vulnerability to HIV. Participants answered questions about demographics, sexual behaviors, and lifetime HIV/STI testing history. Multivariable robust Poisson regression was used to estimate risk ratios (RRs) and 95% confidence intervals (CIs) for factors potentially associated with prior testing. RESULTS: Among 1,014 participants, 348 (34.3%) were TGW and the median age was 21.6 (interquartile range 20.0-24.8) years. Prior testing for HIV was reported by 421 (41.5%) and for other STIs by 268 (26.4%). HIV testing was more common among participants aged ≥ 22 years (RR 1.37 [95% CI 1.13-1.67]), with college education as compared to secondary or less (RR 1.37 [95% CI 1.08-1.72]), and who met male sexual partners online (RR 1.52 [95% CI 1.24-1.85]), but lower among participants attracted to both men and women as compared to men only (RR 0.64 [95% CI 0.51-0.81]) and who met male sexual partners in bars (RR 0.83 [95% CI 0.72-0.97]). Similar associations were observed with prior testing for other STIs, including increased testing among participants with college education (RR 1.52 [95% CI 1.11-2.09]) and who met male sexual partners online (RR 1.73 [95% CI 1.30-2.31]), but lower among participants attracted to both men and women (RR 0.70 [95% CI 0.51-0.96]) and who met male sexual partners in bars (RR 0.67 [95% CI 0.54-0.83]). CONCLUSIONS: Despite behavioral vulnerability, prior testing for HIV and other STIs was uncommon. Online engagement strategies may be effectively reaching Thai MSM and TGW who meet sexual partners online, but new interventions are needed to encourage testing among younger, less educated, and bisexual MSM and TGW.

Knowledge, attitudes, and practices associated with zoonotic disease transmission risk in North Sulawesi, Indonesia.

BACKGROUND: Hunters, vendors, and consumers are key actors in the wildlife trade value chain in North Sulawesi, Indonesia, and potentially face an elevated risk of exposure to zoonotic diseases. Understanding the knowledge, attitudes, and practices (KAP) associated with the risk of zoonotic disease transmission in these communities is therefore critical for developing recommendations to prevent or mitigate zoonotic outbreaks in the future. METHODS: Qualitative and quantitative methods were combined to understand KAP associated zoonotic diseases transmission risk in communities involved in the wildlife trade in North Sulawesi. Qualitative data were collected through semi-structured ethnographic interviews and focus group discussions (FGDs) while quantitative data were collected using questionnaires. We conducted 46 ethnographic interviews and 2 FGDs in 2016, and 477 questionnaire administrations in 2017-2018 in communities from five districts in North Sulawesi. We also collected biological specimens, including nasal swab, oropharyngeal swab, and blood, from 254 participants. The study sites were targeted based on known wildlife consumption and trade activities. The participants for qualitative data collection were purposively selected while participants for quantitative data collection were randomly selected. Biological samples were tested for five viral families including Coronaviridae, Filoviridae, Flaviviridae, Orthomyxoviridae and Paramyxoviridae. RESULTS: Knowledge regarding disease transmission from animals to humans was similar across the participants in qualitative focus groups, including knowledge of rabies and bird flu as zoonotic diseases. However, only a small fraction of the participants from the quantitative group (1%) considered that contact with wild animals could cause sickness. Our biological specimen testing identified a single individual (1/254, 0.004%) who was sampled in 2018 with serological evidence of sarbecovirus exposure. Overall, participants were aware of some level of risk in working with open wounds while slaughtering or butchering an animal (71%) but most did not know what the specific risks were. However, significant differences in the attitudes or beliefs around zoonotic disease risk and health seeking behaviors were observed across our study sites in North Sulawesi. CONCLUSIONS: Our study showed variable levels of knowledge, attitudes, and practices associated with the risk of zoonotic disease transmission among study participants. These findings can be used to develop locally responsive recommendations to mitigate zoonotic disease transmission.

Behavioral-biological surveillance of emerging infectious diseases among a dynamic cohort in Thailand.

BACKGROUND: Interactions between humans and animals are the key elements of zoonotic spillover leading to zoonotic disease emergence. Research to understand the high-risk behaviors associated with disease transmission at the human-animal interface is limited, and few consider regional and local contexts. OBJECTIVE: This study employed an integrated behavioral-biological surveillance approach for the early detection of novel and known zoonotic viruses in potentially high-risk populations, in an effort to identify risk factors for spillover and to determine potential foci for risk-mitigation measures. METHOD: Participants were enrolled at two community-based sites (n = 472) in eastern and western Thailand and two hospital (clinical) sites (n = 206) in northeastern and central Thailand. A behavioral questionnaire was administered to understand participants' demographics, living conditions, health history, and animal-contact behaviors and attitudes. Biological specimens were tested for coronaviruses, filoviruses, flaviviruses, influenza viruses, and paramyxoviruses using pan (consensus) RNA Virus assays. RESULTS: Overall 61/678 (9%) of participants tested positive for the viral families screened which included influenza viruses (75%), paramyxoviruses (15%), human coronaviruses (3%), flaviviruses (3%), and enteroviruses (3%). The most salient predictors of reporting unusual symptoms (i.e., any illness or sickness that is not known or recognized in the community or diagnosed by medical providers) in the past year were having other household members who had unusual symptoms and being scratched or bitten by animals in the same year. Many participants reported raising and handling poultry (10.3% and 24.2%), swine (2%, 14.6%), and cattle (4.9%, 7.8%) and several participants also reported eating raw or undercooked meat of these animals (2.2%, 5.5%, 10.3% respectively). Twenty four participants (3.5%) reported handling bats or having bats in the house roof. Gender, age, and livelihood activities were shown to be significantly associated with participants' interactions with animals. Participants' knowledge of risks influenced their health-seeking behavior. CONCLUSION: The results suggest that there is a high level of interaction between humans, livestock, and wild animals in communities at sites we investigated in Thailand. This study highlights important differences among demographic and occupational risk factors as they relate to animal contact and zoonotic disease risk, which can be used by policymakers and local public health programs to build more effective surveillance strategies and behavior-focused interventions.

Living Safely With Bats: Lessons in Developing and Sharing a Global One Health Educational Resource.

As part of a public health behavior change and communication strategy related to the identification of a novel ebolavirus in bats in Sierra Leone in 2016, a consortium of experts launched an effort to create a widely accessible resource for community awareness and education on reducing disease risk. The resulting picture book, Living Safely With Bats, includes technical content developed by a consortium of experts in public health, animal health, conservation, bats, and disease ecology from 30 countries. The book has now been adapted, translated, and used in more than 20 countries in Africa and Asia. We review the processes used to integrate feedback from local stakeholders and multidisciplinary experts. We also provide recommendations for One Health and other practitioners who choose to pursue the development and evaluation of this or similar zoonotic disease risk mitigation tools.

Environmental Change and Zoonotic Disease Risk at Human-Macaque Interfaces in Bangladesh.

Anthropogenic land-use changes increase the frequency of interactions and habitat overlap between humans and macaques which play an important role in zoonotic disease transmission. This exploratory qualitative study aimed to examine connections between land-use change and macaque-human interactions and assess the chance of zoonotic disease transmission. We conducted ethnographic interviews and focus group discussions in Old Dhaka, Madaripur, and Chandpur, Bangladesh. Participants reported significant anthropogenic landscape transformations leading to increased human-macaque contact in the study areas. Participants also reported that all three sites underwent substantial landscape alteration from natural or agricultural land to a human-altered environment with roads, commercial, and residential buildings. Participants noted that the disappearance of forestland appeared to increase the macaque dependence on backyard fruit trees. Where rivers and ponds were filled to support local construction, macaques were also observed as becoming more dependent upon human water sources. These changed may help expanding the macaques' foraging areas, and they appear to be invading new areas where people are not culturally habituated to living with them. In response, many residents reported reacting aggressively toward the macaques, which they believed led to more bites and scratches. However, other respondents accepted the presence of macaques around their homes. Few participants considered macaques to be a source of disease transmission. This study revealed that local environmental changes, deforestation, urban expansion, construction, and water bodies' disappearance are linked to increasing human-macaque interactions. Understanding these interactions is critical to develop successful mitigation interventions at interfaces with a high risk for viral disease spillover.

Risk Factors for HIV sero-conversion in a high incidence cohort of men who have sex with men and transgender women in Bangkok, Thailand.

BACKGROUND: We measured Human Immunodeficiency (HIV) incidence, retention, and assessed risk factors for seroconversion among two previously unreported cohorts of men who have sex with men (MSM) and Transgender Women (TGW) in Bangkok, Thailand between 2017 and 2019. METHODS: We conducted an 18-month prospective cohort study of HIV-uninfected Thai cisgender men and TGW aged between 18 and 35 years who reported sex with men in the past six months and at least one additional risk factor for HIV infection. HIV and syphilis testing and computer-based behavioral questionnaires were administered at each visit. We utilized Poisson regression to calculate HIV incidence rates. A survival random forest model identified the most predictive risk factors for HIV sero-conversion and then used in a survival regression tree model to elucidate hazard ratios for individuals with groups of selected risk factors. Cox proportional hazards (pH) regression evaluated the strength of association between individual covariates and risk of sero-conversion. FINDINGS: From April 2017-October 2019, 1,184 participants were screened, 167 were found ineligible, and 1,017 enrolled. Over the 18-month study, visit retention was 93·4% (95% CI 91·6%-94·8%) and HIV incidence was 3·73 per 100 person-years (95% CI 2·79-5·87). Utilizing survival regression tree modeling, those who were 18-20 years of age, reported sexual attraction to mostly or only men, and had five or more lifetime sexual partners were 4·9 times more likely to seroconvert compared to other cohort participants. Factors associated with HIV incidence utilizing Cox pH regression included sexual attraction to mostly or only men (adjusted hazard ratio (aHR) 14·9 (95% CI 20·1-107·9), younger age (18-19 years, aHR 10·88 (95% CI 4·12-28·7), five or greater lifetime sexual partners (aHR 2·0, 95%CI 1·1-3·6), inconsistent condom use with casual partners (aHR 2·43, 95% CI 1·3-4·5), and prior HIV testing (adjusted HR 2·0, 95% CI 1·1-3·5). INTERPRETATION: Interpretation HIV incidence remains high among Bangkok-based MSM and TGW. These key populations expressed high interest in participating in efficacy evaluation of future prevention strategies and had high retention in this 18 month study. FUNDING: Funding US National Institute of Allergy and Infectious Diseases (NIAID), Division of AIDS Interagency Agreements (DAIDS) and U.S. Department of the Army.

Socializing One Health: an innovative strategy to investigate social and behavioral risks of emerging viral threats.

In an effort to strengthen global capacity to prevent, detect, and control infectious diseases in animals and people, the United States Agency for International Development's (USAID) Emerging Pandemic Threats (EPT) PREDICT project funded development of regional, national, and local One Health capacities for early disease detection, rapid response, disease control, and risk reduction. From the outset, the EPT approach was inclusive of social science research methods designed to understand the contexts and behaviors of communities living and working at human-animal-environment interfaces considered high-risk for virus emergence. Using qualitative and quantitative approaches, PREDICT behavioral research aimed to identify and assess a range of socio-cultural behaviors that could be influential in zoonotic disease emergence, amplification, and transmission. This broad approach to behavioral risk characterization enabled us to identify and characterize human activities that could be linked to the transmission dynamics of new and emerging viruses. This paper provides a discussion of implementation of a social science approach within a zoonotic surveillance framework. We conducted in-depth ethnographic interviews and focus groups to better understand the individual- and community-level knowledge, attitudes, and practices that potentially put participants at risk for zoonotic disease transmission from the animals they live and work with, across 6 interface domains. When we asked highly-exposed individuals (ie. bushmeat hunters, wildlife or guano farmers) about the risk they perceived in their occupational activities, most did not perceive it to be risky, whether because it was normalized by years (or generations) of doing such an activity, or due to lack of information about potential risks. Integrating the social sciences allows investigations of the specific human activities that are hypothesized to drive disease emergence, amplification, and transmission, in order to better substantiate behavioral disease drivers, along with the social dimensions of infection and transmission dynamics. Understanding these dynamics is critical to achieving health security--the protection from threats to health-- which requires investments in both collective and individual health security. Involving behavioral sciences into zoonotic disease surveillance allowed us to push toward fuller community integration and engagement and toward dialogue and implementation of recommendations for disease prevention and improved health security.

A qualitative study of zoonotic risk factors among rural communities in southern China.

BACKGROUND: Strategies are urgently needed to mitigate the risk of zoonotic disease emergence in southern China, where pathogens with zoonotic potential are known to circulate in wild animal populations. However, the risk factors leading to emergence are poorly understood, which presents a challenge in developing appropriate mitigation strategies for local communities. METHODS: Residents in rural communities of Yunnan, Guangxi and Guangdong provinces were recruited and enrolled in this study. Data were collected through ethnographic interviews and field observations, and thematically coded and analysed to identify both risk and protective factors for zoonotic disease emergence at the individual, community and policy levels. RESULTS: Eighty-eight ethnographic interviews and 55 field observations were conducted at nine selected sites. Frequent human-animal interactions and low levels of environmental biosecurity in local communities were identified as risks for zoonotic disease emergence. Policies and programmes existing in the communities provide opportunities for zoonotic risk mitigation. CONCLUSIONS: This study explored the relationship among zoonotic risk and human behaviour, environment and policies in rural communities in southern China. It identifies key behavioural risk factors that can be targeted for development of tailored risk-mitigation strategies to reduce the threat of novel zoonoses.

Findings from the SASA! Study: a cluster randomized controlled trial to assess the impact of a community mobilization intervention to prevent violence against women and reduce HIV risk in Kampala, Uganda.

BACKGROUND: Intimate partner violence (IPV) and HIV are important and interconnected public health concerns. While it is recognized that they share common social drivers, there is limited evidence surrounding the potential of community interventions to reduce violence and HIV risk at the community level. The SASA! study assessed the community-level impact of SASA!, a community mobilization intervention to prevent violence and reduce HIV-risk behaviors. METHODS: From 2007 to 2012 a pair-matched cluster randomized controlled trial (CRT) was conducted in eight communities (four intervention and four control) in Kampala, Uganda. Cross-sectional surveys of a random sample of community members, 18- to 49-years old, were undertaken at baseline (n = 1,583) and four years post intervention implementation (n = 2,532). Six violence and HIV-related primary outcomes were defined a priori. An adjusted cluster-level intention-to-treat analysis compared outcomes in intervention and control communities at follow-up. RESULTS: The intervention was associated with significantly lower social acceptance of IPV among women (adjusted risk ratio 0.54, 95% confidence interval (CI) 0.38 to 0.79) and lower acceptance among men (0.13, 95% CI 0.01 to 1.15); significantly greater acceptance that a woman can refuse sex among women (1.28, 95% CI 1.07 to 1.52) and men (1.31, 95% CI 1.00 to 1.70); 52% lower past year experience of physical IPV among women (0.48, 95% CI 0.16 to 1.39); and lower levels of past year experience of sexual IPV (0.76, 95% CI 0.33 to 1.72). Women experiencing violence in intervention communities were more likely to receive supportive community responses. Reported past year sexual concurrency by men was significantly lower in intervention compared to control communities (0.57, 95% CI 0.36 to 0.91). CONCLUSIONS: This is the first CRT in sub-Saharan Africa to assess the community impact of a mobilization program on the social acceptability of IPV, the past year prevalence of IPV and levels of sexual concurrency. SASA! achieved important community impacts, and is now being delivered in control communities and replicated in 15 countries. TRIAL REGISTRATION: ClinicalTrials.gov #NCT00790959.

The changing cultural and economic dynamics of polygyny and concurrent sexual partnerships in Iringa, Tanzania.

Polygyny has been identified both as a 'benign' form of concurrency and as the cultural basis of concurrent partnerships that are considered important drivers of the HIV epidemic in sub-Saharan Africa. This paper investigates the changing cultural and economic dynamics of polygyny in concurrency in Iringa, Tanzania, a region with traditions of polygyny and high prevalence of HIV. Our analysis of focus group discussions, in-depth interviews and key informant interviews indicate that contemporary concurrent partnerships differ from regional traditions of polygyny. Whereas in the past, polygyny reflected men's and their kin group's wealth and garnered additional prestige, polygyny today is increasingly seen as a threat to health, and as leading to poverty. Nevertheless, participants evoked the social prestige of polygyny to explain men's present-day concurrency, even outside the bounds of marriage, and despite continued social prohibitions against extramarital affairs. Difficult economic conditions, combined with this prestige, made it easier for men to engage in concurrency without the considerable obligations to wives and children in polygyny. Local economic conditions also compelled women to seek concurrent partners to meet basic needs and to access consumer goods, but risked greater moral judgement than men, especially if deemed to have excessive 'desire' for money.