A new piece of the microbiota pie: Mining 'omics for DNA inversion states.

In this issue of Cell Host & Microbe, Carasso et al. survey invertible DNA sites in Bacteroidales from patients with inflammatory bowel disease (IBD) and healthy control individuals. They identify complex functional interactions between Bacteroides fragilis, an invertible promoter, a capsular polysaccharide, a bacteriophage, and the human host. The establishment of 'omics approaches to characterizing genomic targets and functional roles is still required.

Safety and Immune Responses Following Anti-PD-1 Monoclonal Antibody Infusions in Healthy Persons With Human Immunodeficiency Virus on Antiretroviral Therapy.

Background: T cells in people with human immunodeficiency virus (HIV) demonstrate an exhausted phenotype, and HIV-specific CD4+ T cells expressing programmed cell death 1 (PD-1) are enriched for latent HIV, making antibody to PD-1 a potential strategy to target the latent reservoir. Methods: This was a phase 1/2, randomized (4:1), double-blind, placebo-controlled study in adults with suppressed HIV on antiretroviral therapy with CD4+ counts ≥350 cells/µL who received 2 infusions of cemiplimab versus placebo. The primary outcome was safety, defined as any grade 3 or higher adverse event (AE) or any immune-related AE (irAE). Changes in HIV-1-specific polyfunctional CD4+ and CD8+ T-cell responses were evaluated. Results: Five men were enrolled (median CD4+ count, 911 cells/µL; median age, 51 years); 2 received 1 dose of cemiplimab, 2 received 2 doses, and 1 received placebo. One participant had a probable irAE (thyroiditis, grade 2); another had a possible irAE (hepatitis, grade 3), both after a single low-dose (0.3 mg/kg) infusion. The Safety Monitoring Committee recommended no further enrollment or infusions. All 4 cemiplimab recipients were followed for 48 weeks. No other cemiplimab-related serious AEs, irAEs, or grade 3 or higher AEs occurred. One 2-dose recipient of cemiplimab had a 6.2-fold increase in polyfunctional, Gag-specific CD8+ T-cell frequency with supportive increases in plasma HIV RNA and decreases in total HIV DNA. Conclusions: One of 4 participants exhibited increased HIV-1-specific T-cell responses and transiently increased HIV-1 expression following 2 cemiplimab infusions. The occurrence of irAEs after a single, low dose may limit translating the promising therapeutic results of cemiplimab for cancer to immunotherapeutic and latency reversal strategies for HIV. Clinical Trials Registration. NCT03787095.

Horizontal Gene Transfer and CRISPR Targeting Drive Phage-Bacterial Host Interactions and Coevolution in "Pink Berry" Marine Microbial Aggregates.

Bacteriophages (phages), which are viruses that infect bacteria, are the most abundant components of microbial communities and play roles in community dynamics and host evolution. However, the study of phage-host interactions is hindered by a paucity of model systems from natural environments. Here, we investigate phage-host interactions in the "pink berry" consortia, which are naturally occurring, low-diversity, macroscopic bacterial aggregates that are found in the Sippewissett Salt Marsh (Falmouth, MA, USA). We leverage metagenomic sequence data and a comparative genomics approach to identify eight compete phage genomes, infer their bacterial hosts from host-encoded clustered regularly interspaced short palindromic repeats (CRISPRs), and observe the potential evolutionary consequences of these interactions. Seven of the eight phages identified infect known pink berry symbionts, namely, Desulfofustis sp. PB-SRB1, Thiohalocapsa sp. PB-PSB1, and Rhodobacteraceae sp. A2, and they are largely divergent from known viruses. In contrast to the conserved bacterial community structure of pink berries, the distribution of these phages across aggregates is highly variable. Two phages persisted over a period of seven years with high sequence conservation, allowing us to identify gene gain and loss. Increased nucleotide variation in a conserved phage capsid gene that is commonly targeted by host CRISPR systems suggests that CRISPRs may drive phage evolution in pink berries. Finally, we identified a predicted phage lysin gene that was horizontally transferred to its bacterial host, potentially via a transposon intermediary. Taken together, our results demonstrate that pink berry consortia contain diverse and variable phages as well as provide evidence for phage-host coevolution via multiple mechanisms in a natural microbial system. IMPORTANCE Phages, which are viruses that infect bacteria, are important components of all microbial systems, in which they drive the turnover of organic matter by lysing host cells, facilitate horizontal gene transfer (HGT), and coevolve with their bacterial hosts. Bacteria resist phage infection, which is often costly or lethal, through a diversity of mechanisms. One of these mechanisms is CRISPR systems, which encode arrays of phage-derived sequences from past infections to block subsequent infection with related phages. Here, we investigate the bacteria and phage populations from a simple marine microbial community, known as "pink berries", found in salt marshes of Falmouth, Massachusetts, as a model of phage-host coevolution. We identify eight novel phages and characterize a case of putative CRISPR-driven phage evolution as well as an instance of HGT between a phage and its host, together suggesting that phages have large evolutionary impacts in a naturally occurring microbial community.

A Trauma-Informed HIV Intervention (LinkPositively) to Improve HIV Care Among Black Women Affected by Interpersonal Violence: Protocol for a Pilot Randomized Controlled Trial.

BACKGROUND: Black women bear a disproportionate burden of HIV, accounting for nearly 60% of new diagnoses among US women. Black women living with HIV often experience mutually reinforcing epidemics, known as syndemics, including interpersonal violence and substance use. Syndemics are associated with decreased HIV care engagement and treatment adherence and worsening HIV outcomes. Few HIV services and resources are tailored to be culturally and gender-responsive and trauma informed for Black women living with HIV. Technology-based, psychoeducational, and peer navigation programs offer promising pathways to tailored HIV support and improved HIV care outcomes. Therefore, the web-based, trauma-informed intervention LinkPositively was developed in collaboration with Black women living with HIV to promote uptake of HIV care and ancillary support services. OBJECTIVE: This study primarily determines the feasibility and acceptability of the LinkPositively intervention among Black women living with HIV affected by interpersonal violence. The secondary aim is to examine the preliminary impact of the LinkPositively intervention on retention in HIV care, antiretroviral therapy adherence, and viral suppression while evaluating the role of mechanism of change variables (eg, social support) in the associations. METHODS: The LinkPositively trial is a pilot randomized controlled trial conducted in California, United States, among 80 adult Black women living with HIV who have experienced interpersonal violence. Core components of LinkPositively include one-on-one peer navigation with phone and SMS text message check-ins; 5 weekly one-on-one video sessions to build coping and care navigation skills; and a mobile app that contains a peer support social networking platform, an educational database with healthy living and self-care tips, a GPS-enabled HIV and ancillary care resource locator, and a medication self-monitoring and reminder system. Participants are randomly assigned to the intervention (n=40) or control (Ryan White standard of care; n=40) arm, with follow-up at 3 and 6 months. At each assessment, participants complete an interviewer-administered survey and submit hair samples for the assessment of HIV medication adherence. All research staff and investigators adhere to ethical principles and guidelines for conducting research activities. Data will be analyzed using generalized estimating equations. RESULTS: Final development and testing of the LinkPositively app were completed in July 2021. As of May 2023, we have screened 97 women for eligibility. Of the 97 women screened, 27 (28%) were eligible and have been enrolled in the study. The dissemination of preliminary results will occur in 2024. CONCLUSIONS: This trial will advance HIV prevention science by harnessing technology to promote engagement in HIV care while improving social support through peers and social networking-all while being trauma informed for Black women living with HIV with experiences of interpersonal violence. If shown to be feasible and acceptable, LinkPositively has the potential to improve HIV care outcomes among Black women, a marginalized key population. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/46325.

An examination of the association between forced sex history and reproductive coercion experiences among Black women attending STD clinics in Baltimore, MD, USA.

BACKGROUND: Reproductive coercion victimization (RCV) is a significant public health issue that negatively affects women's sexual and reproductive health outcomes. Less is known about reproductive coercion perpetration (RCP). Few studies have examined these phenomena among representative samples of Black women. METHODS: Retrospective data of women (n = 298) attending STD clinics in Baltimore, MD were analyzed. We calculated lifetime and 12-month prevalence reports of reproductive coercion, and reported values stratified by forced sex history. Binomial logistic regression models were used to examine the association between forced sex history and RCV, accounting for other types of violence typologies. RESULTS: Lifetime and past 12-month RCV and RCP prevalence were higher among women with forced sex experiences than their counterparts (Lifetime RCV: 46.9% versus 17.5%; past 12-month RCV: 19.4% versus 8.5%. Lifetime RCP: 24.5% versus 17%; past 12-month RCP: 13.3% versus 10.5%). Adjusted models, lifetime reproductive coercion: Women reporting forced sex had a 3.58 times higher odds of having had experienced RCV compared to women not reporting forced sex (AOR 3.58; 95% CI 2.00, 6.46). Women reporting forced sex had a 3.66 times higher odds of having ever experienced pregnancy coercion compared to their counterparts (AOR 3.66; 95% CI 1.93, 7.03) and 4.30 times higher odds of having ever experienced condom manipulation (AOR 4.30; 95% CI 2.15, 8.86). Adjusted models, past 12-month reproductive coercion: Women reporting forced sex had a 2.72 times higher odds of having had experienced past 12-month RCV compared to women not reporting forced sex (AOR 2.72; 95% CI 1.27, 5.91). Women reporting forced sex had a 3.25 times higher odds of having experienced past 12-month pregnancy coercion compared to their counterparts (AOR 3.25; 95% CI 1.38, 7.83) and 3.41 times higher odds of having experienced past 12-month condom manipulation (AOR 3.41; 95% CI 1.14, 10.98). CONCLUSIONS: Participants in our study reported high rates of RCV. Our novel exploration revealed significantly high rates of co-occurring forced sex experiences and RCV and initial prevalence report of RCP. Agencies have a unique opportunity to intervene by implementing screening protocols and referrals for supportive services. These findings may inform future intervention research efforts aimed at improving reproductive health outcomes among Black women.

Impact of the Microbiota on Viral Infections.

The mammalian gastrointestinal tract (GIT) hosts a diverse and highly active microbiota composed of bacteria, eukaryotes, archaea, and viruses. Studies of the GIT microbiota date back more than a century, although modern techniques, including mouse models, sequencing technology, and novel therapeutics in humans, have been foundational to our understanding of the roles of commensal microbes in health and disease. Here, we review the impacts of the GIT microbiota on viral infection, both within the GIT and systemically. GIT-associated microbes and their metabolites alter the course of viral infection through a variety of mechanisms, including direct interactions with virions, alteration of the GIT landscape, and extensive regulation of innate and adaptive immunity. Mechanistic understanding of the full breadth of interactions between the GIT microbiota and the host is still lacking in many ways but will be vital for the development of novel therapeutics for viral and nonviral diseases alike.

Evaluating the feasibility of implementing a prescription drug misuse prevention intervention in the community: a mixed methods study.

BACKGROUND: This study is part of a state-wide effort to promote the safe disposal of prescription medications and mitigate prescription drug misuse. The objective of this study was to evaluate the implementation of a two-component prevention intervention through Community Prevention Organizations (CPOs) in Texas. The first component involved the distribution of in-home disposal products (IHDP) and the second focused on providing education of the risks of prescription drug misuse. METHODS: This study followed a mixed methods sequential explanatory study design. In the quantitative phase, the extent to which CPOs carried out the intervention was determined by the distribution rate - a proportion representing the number of IHDP distributed to end users from the amount of IHDP the CPO was shipped. This measure was used to organize the CPOs in to one of three performance categories. In the qualitative arm of the study, stratified random sampling was used to select five CPOs from each performance strata to participate in an in-depth, semi-structured interview about their distribution activity. The interview guide and the data analysis were guided by Bowen's Feasibility Framework. The interviews were transcribed and analyzed using a content analysis approach by two research team members. All qualitative analyses were conducted in ATLAS.ti© V7. RESULTS: There was a total of 47 CPOs contacted and asked to be part of this study. Of them, 44 CPOs participated in the quantitative phase of the study. This phase revealed that all CPOs had existing relationships with organizations throughout the community such as pharmacies and schools that could act as points of distribution. Following the quantitative phase, 15 CPOs were selected for more in-depth interviews about their distribution practices. In the qualitative phase, this finding was reinforced through the theme "partnerships with local institutions and ability to implement the intervention at community events". Similarly, education promotion efforts were unanimously emphasized as a strategy to increase utilization of IHDP among end users. All CPOs indicated that the intervention was supplemental to their overall goals. CONCLUSION: CPOs have unparalleled access to community events, local institutions, and the general population they serve, thus, they have the potential to be active facilitators in implementing prevention interventions.

Horizontal gene transfer and CRISPR targeting drive phage-bacterial host interactions and coevolution in pink berry marine microbial aggregates.

Bacteriophages (phages), viruses that infect bacteria, are the most abundant components of microbial communities and play roles in community dynamics and host evolution. The study of phage-host interactions, however, is made difficult by a paucity of model systems from natural environments and known and cultivable phage-host pairs. Here, we investigate phage-host interactions in the "pink berry" consortia, naturally-occurring, low-diversity, macroscopic aggregates of bacteria found in the Sippewissett Salt Marsh (Falmouth, MA, USA). We leverage metagenomic sequence data and a comparative genomics approach to identify eight compete phage genomes, infer their bacterial hosts from host-encoded clustered regularly interspaced short palindromic repeats (CRISPR), and observe the potential evolutionary consequences of these interactions. Seven of the eight phages identified infect the known pink berry symbionts Desulfofustis sp. PB-SRB1, Thiohalocapsa sp. PB-PSB1, and Rhodobacteraceae sp. A2, and belong to entirely novel viral taxa, except for one genome which represents the second member of the Knuthellervirus genus. We further observed increased nucleotide variation over a region of a conserved phage capsid gene that is commonly targeted by host CRISPR systems, suggesting that CRISPRs may drive phage evolution in pink berries. Finally, we identified a predicted phage lysin gene that was horizontally transferred to its bacterial host, potentially via a transposon intermediary, emphasizing the role of phages in bacterial evolution in pink berries. Taken together, our results demonstrate that pink berry consortia contain diverse and variable phages, and provide evidence for phage-host co-evolution via multiple mechanisms in a natural microbial system. IMPORTANCE: Phages (viruses that infect bacteria) are important components of all microbial systems, where they drive the turnover of organic matter by lysing host cells, facilitate horizontal gene transfer (HGT), and co-evolve with their bacterial hosts. Bacteria resist phage infection, which is often costly or lethal, through a diversity of mechanisms. One of these mechanisms are CRISPR systems, which encode arrays of phage-derived sequences from past infections to block subsequent infection with related phages. Here, we investigate bacteria and phage populations from a simple marine microbial community known as "pink berries" found in salt marshes of Falmouth, Massachusetts, as a model of phage-host co-evolution. We identify eight novel phages, and characterize a case of putative CRISPR-driven phage evolution and an instance of HGT between phage and host, together suggesting that phages have large evolutionary impacts in a naturally-occuring microbial community.

"It comes altogether as one:" perceptions of analytical treatment interruptions and partner protections among racial, ethnic, sex and gender diverse HIV serodifferent couples in the United States.

BACKGROUND: Most HIV cure-related studies involve interrupting antiretroviral treatment to assess the efficacy of pharmacologic interventions - also known as analytical treatment interruptions (ATIs). ATIs imply the risk of passing HIV to sexual partners due to the loss of undetectable HIV status. There has been a notable lack of attention paid to perceptions of ATIs among racial, ethnic, sex and gender minorities, and HIV serodifferent couples. These populations are among those most impacted by HIV in the United States. Future HIV cure research paradigms should equitably include considerations from these groups. METHODS: From August - October 2020, we conducted in-depth interviews with 10 racial, ethnic, sex, and gender minority HIV serodifferent couples in geographically diverse regions of the United States to understand their perspectives about ATIs and partner protection measures to prevent secondary HIV transmissions because of participation in ATI studies. We used framework analysis to analyze the qualitative data. RESULTS: Of the 10 couples recruited, four identified as a gay couple, two as a gay and bisexual couple, two as a heterosexual couple, one as a gay and queer couple, and one as a queer couple. We found that HIV serodifferent couples in our study viewed ATIs as contradicting HIV treatment adherence messages. Couples expressed discomfort around ATIs in HIV cure research. They were concerned with the return of HIV detectability and worried ATIs might result in secondary HIV transmission. Participants were strongly in favor of using a range of partner protection measures during ATIs that included PrEP, HIV risk reduction counseling, and alternatives for penetrative sex practices. Couples also recommended that sex partners be consulted or involved as part of ATI trials. CONCLUSIONS: Our findings highlight new potential opportunities and strategies to mitigate risk of HIV transmission during ATIs among key groups historically under-represented in HIV cure research. Findings also underscore the relational aspects of ATI trials. We provide preliminary considerations for planning ATI trials with diverse HIV serodifferent partners. Future studies should continue to explore these issues among other types of partnerships, cultures, and socio-cultural settings.

Colchicine for the Treatment of Cardiac Injury in Hospitalized Patients With Coronavirus Disease-19.

Introduction: The impact of colchicine on hospitalized patients with Coronavirus disease-19 (COVID-19) related cardiac injury is unknown. Materials and Methods: In this multicenter randomized controlled open-label clinical trial, we randomized hospitalized adult patients with documented COVID-19 and evidence of cardiac injury in a 1:1 ratio to either colchicine 0.6 mg po twice daily for 30 days plus standard of care or standard of care alone. Cardiac injury was defined as elevated cardiac biomarkers, new arrhythmia, new/worsened left ventricular dysfunction, or new pericardial effusion. The primary endpoint was the composite of all-cause mortality, need for mechanical ventilation, or need for mechanical circulatory support (MCS) at 90 days. Key secondary endpoints included the individual components of the primary endpoint and change in and at least 2-grade reduction in the World Health Organization (WHO) Ordinal Scale at 30 days. The trial is registered with clinicaltrials.gov (NCT04355143). Results: We enrolled 93 patients, 48 patients in the colchicine arm and 45 in the control arm. There was no significant difference in the primary outcome between the colchicine and control arms (19 vs. 15%, p = 0.78), nor in the individual components of all-cause mortality (17 vs. 15%, p = 1.0) and need for mechanical ventilation (8 vs. 5%, p = 0.68); no patients in either group required MCS. The change in (-1.8 ± 2.4 vs. -1.2 ± 2.0, p = 0.12) and at least 2-grade reduction (75 vs. 75%, p = 1.0) in the WHO ordinal scale was also similar between groups. Conclusion: Patients hospitalized with COVID-19 and evidence of cardiac injury did not benefit from colchicine therapy.

A Path FORWARD: Development of a Comprehensive Multidisciplinary Clinic to Create Health and Wellness for the Child and Adolescent with a Fontan Circulation.

Today, it is anticipated most individuals diagnosed with single-ventricle malformation will survive surgical reconstruction through a successful Fontan operation. As greater numbers of patients survive, so has the recognition that individuals with Fontan circulation face a variety of challenges. The goal of a normal quality and duration of life will not be reached by all. The hurdles fall into a variety of domains. From a cardiovascular perspective, the Fontan circulation is fundamentally flawed by its inherent nature of creating a state of chronically elevated venous pressure and congestion, accompanied by a relatively low cardiac output. Ventricular dysfunction, atrioventricular valve regurgitation, and arrhythmia may directly impact cardiac performance and can progress with time. Problems are not limited to the cardiovascular system. Fontan circulatory physiology impacts a multitude of biological processes and health parameters outside the heart. The lymphatic circulation is under strain manifesting as variable degrees of protein-rich lymph loss and immune system dysregulation. Organ system dysfunction develops through altered perfusion profiles. Liver fibrosis is ubiquitous, and a process of systemic fibrogenesis in response to circulatory stressors may affect other organs as well. Somatic growth and development can be delayed. Behavioral and mental health problems are common, presenting as clinically important levels of anxiety and depression. Most striking is the high variability in prevalence and magnitude of these complications within the population, indicating the likelihood of additional factors enhancing or mitigating their emergence. We propose that optimal care for the individual with single ventricle and a Fontan circulation is ideally offered in a comprehensive multidisciplinary manner, with attention to elements that are beyond cardiac management alone. In this report, we share the concepts, our experiences, and perspectives on development of a clinic model-the "Fontan rehabilitation, wellness and resilience development" or FORWARD program. We provide insights into the mechanics of our multidisciplinary model of care and the benefits offered serving our growing population of individuals with a Fontan circulation and their families.

Preliminary Acceptability of a Home-Based Peripheral Blood Collection Device for Viral Load Testing in the Context of Analytical Treatment Interruptions in HIV Cure Trials: Results from a Nationwide Survey in the United States.

Frequent viral load testing is necessary during analytical treatment interruptions (ATIs) in HIV cure-directed clinical trials, though such may be burdensome and inconvenient to trial participants. We implemented a national, cross-sectional survey in the United States to examine the acceptability of a novel home-based peripheral blood collection device for HIV viral load testing. Between June and August 2021, we distributed an online survey to people with HIV (PWH) and community members, biomedical HIV cure researchers and HIV care providers. We performed descriptive analyses to summarize the results. We received 73 survey responses, with 51 from community members, 12 from biomedical HIV cure researchers and 10 from HIV care providers. Of those, 51 (70%) were cisgender men and 50 (68%) reported living with HIV. Most (>80% overall) indicated that the device would be helpful during ATI trials and they would feel comfortable using it themselves or recommending it to their patients/participants. Of the 50 PWH, 42 (84%) indicated they would use the device if they were participating in an ATI trial and 27 (54%) also expressed a willingness to use the device outside of HIV cure studies. Increasing sensitivity of viral load tests and pluri-potency of the device (CD4 count, chemistries) would augment acceptability. Survey findings provide evidence that viral load home testing would be an important adjunct to ongoing HIV cure-directed trials involving ATIs. Survey findings may help inform successful implementation and uptake of the device in the context of personalized HIV care.

Single-cell genomics for resolution of conserved bacterial genes and mobile genetic elements of the human intestinal microbiota using flow cytometry.

As our understanding of the importance of the human microbiota in health and disease grows, so does our need to carefully resolve and delineate its genomic content. 16S rRNA gene-based analyses yield important insights into taxonomic composition, and metagenomics-based approaches reveal the functional potential of microbial communities. However, these methods generally fail to directly link genetic features, including bacterial genes and mobile genetic elements, to each other and to their source bacterial genomes. Further, they are inadequate to capture the microdiversity present within a genus, species, or strain of bacteria within these complex communities. Here, we present a method utilizing fluorescence-activated cell sorting for isolation of single bacterial cells, amplifying their genomes, screening them by 16S rRNA gene analysis, and selecting cells for genomic sequencing. We apply this method to both a cultured laboratory strain of Escherichia coli and human stool samples. Our analyses reveal the capacity of this method to provide nearly complete coverage of bacterial genomes when applied to isolates and partial genomes of bacterial species recovered from complex communities. Additionally, this method permits exploration and comparison of conserved and variable genomic features between individual cells. We generate assemblies of novel genomes within the Ruminococcaceae family and the Holdemanella genus by combining several 16S rRNA gene-matched single cells, and report novel prophages and conjugative transposons for both Bifidobacterium and Ruminococcaceae. Thus, we demonstrate an approach for flow cytometric separation and sequencing of single bacterial cells from the human microbiota, which yields a variety of critical insights into both the functional potential of individual microbes and the variation among those microbes. This method definitively links a variety of conserved and mobile genomic features, and can be extended to further resolve diverse elements present in the human microbiota.

Considerations for Increasing Racial, Ethnic, Gender, and Sexual Diversity in HIV Cure-Related Research with Analytical Treatment Interruptions: A Qualitative Inquiry.

Despite disproportionate incidence and prevalence of HIV among transgender individuals, cisgender women, and racial and ethnic minority groups, all remain underrepresented in HIV cure research. As HIV cure trials are scaled up, there is emerging research on ways to mitigate risks of HIV acquisition for sexual partners of analytical treatment interruption (ATI) trial participants. As such, it is imperative that HIV cure researchers consider the implications of implementing ATIs in populations that are disproportionately affected by HIV, but largely underrepresented in trials to date. In this qualitative study, we sought to derive triangulated perspectives on the social and ethical implications regarding ATIs and partner protection strategies during ATIs among under-represented populations. We conducted 21 in-depth interviews with 5 types of informants: bioethicists, community members [people living with HIV (PLWH) and their advocates], biomedical HIV cure researchers, sociobehavioral scientists, and HIV care providers. We analyzed the data using conventional content analysis and reduced the data to important considerations for implementing ATI trials in diverse communities and settings. Our study revealed the following key themes: (1) attention must be paid to gender and power dynamics in ATI trials; (2) ATI trials should be designed and implemented through the lenses of intersectionality and equity frameworks; (3) ATI trials may have both positive and negative effects on stigma for PLWH and their partners; and (4) partnership dynamics should be considered when designing ATI protocols. Our study generated actionable considerations that could be implemented in ATI trials to promote their acceptability to communities that have been underrepresented in HIV cure research to date. Research teams must invest in robust community and stakeholder engagement to define best practices. Paying attention to representation and equity will also promote better and more equitable implementation of HIV cure strategies once these become ready for rollout.

Draft Genome Sequence of Scheffersomyces spartinae ARV011, a Marine Yeast Isolate.

We report the draft genome sequence of Scheffersomyces spartinae ARV011, which was isolated from the Great Sippewissett Marsh in Falmouth, Massachusetts. Sequencing was performed using the Illumina NovaSeq 6000 platform, yielding 7,598,030 read pairs 250 bp in length. This resulted in a total draft genome size of 12,132,557 bp.

NSW Health COVID-19 Emergency Response Priority Research program: a case study of rapid translation of research into health decision making.

OBJECTIVES: The NSW Health COVID-19 Research Program was established in April 2020 to contribute to minimising the health, social and economic impacts of the coronavirus disease 2019 (COVID-19) pandemic in New South Wales (NSW). This paper describes the establishment and implemention of one element of the Program, the Emergency Response Priority Research (Emergency Response) workstream, which is focused on the rapid creation of evidence to support urgent operational work for the public health management of COVID-19 in NSW. METHODS: Narrative description. RESULTS: As at June 2021, nine Emergency Response projects had been funded. Mechanisms used to expedite projects included: embedding academic researchers in NSW Health to work directly with routinely collected NSW Health data; adapting existing research projects to include a COVID-19 component; leveraging established research partnerships to conduct rapid pilots; and directly commissioning urgent projects with experienced and trusted local researchers. LESSONS LEARNT: Evidence from Emergency Response projects has contributed directly to informing the NSW public health response. For example, findings from a study of COVID-19 transmission in schools and childcare settings in the early stages of the pandemic informed decisions around the resumption of on-campus education in 2020 and helped shape policy around higher risk activities to help reduce transmission in education settings. Similarly, findings from a project to validate methods for identifying SARS-CoV-2 virus fragments in wastewater were subsequently incorporated into the NSW Sewage Surveillance Program, which continues to provide NSW Health with information to support targeted messaging and testing. The approach to establishing and implementing the Emergency Response workstream highlights the importance of continuing to ensure a well-trained public health research community and actively supporting a collaborative research sector.

Ethics of HIV cure research: an unfinished agenda.

BACKGROUND: The pursuit of a cure for HIV is a high priority for researchers, funding agencies, governments and people living with HIV (PLWH). To date, over 250 biomedical studies worldwide are or have been related to discovering a safe, effective, and scalable HIV cure, most of which are early translational research and experimental medicine. As HIV cure research increases, it is critical to identify and address the ethical challenges posed by this research. METHODS: We conducted a scoping review of the growing HIV cure research ethics literature, focusing on articles published in English peer-reviewed journals from 2013 to 2021. We extracted and summarized key developments in the ethics of HIV cure research. Twelve community advocates actively engaged in HIV cure research provided input on this summary and suggested areas warranting further ethical inquiry and foresight via email exchange and video conferencing. DISCUSSION: Despite substantial scholarship related to the ethics of HIV cure research, additional attention should focus on emerging issues in six categories of ethical issues: (1) social value (ongoing and emerging biomedical research and scalability considerations); (2) scientific validity (study design issues, such as the use of analytical treatment interruptions and placebos); (3) fair selection of participants (equity and justice considerations); (4) favorable benefit/risk balance (early phase research, benefit-risk balance, risk perception, psychological risks, and pediatric research); (5) informed consent (attention to language, decision-making, informed consent processes and scientific uncertainty); and (6) respect for enrolled participants and community (perspectives of people living with HIV and affected communities and representation). CONCLUSION: HIV cure research ethics has an unfinished agenda. Scientific research and bioethics should work in tandem to advance ethical HIV cure research. Because the science of HIV cure research will continue to rapidly advance, ethical considerations of the major themes we identified will need to be revisited and refined over time.