New Pathways in Syphilis Vaccine Development.

ABSTRACT: The New Pathways in Syphilis Vaccine Development meeting was held prior to the start of the STI & HIV 2023 World Congress as a pre-meeting symposium to highlight recent advances in the development of an effective syphilis vaccine and discuss the challenges still faced by investigators. Internationally renowned public health officials, clinical investigators, and basic researchers from academia, government, and community-based organizations met on the 24th of July 2023 in Chicago, Illinois. Four speakers discussed key research findings in syphilis vaccine development, which included antigen selection, identification of epitopes associated with protective immunity, and delivery platforms, with great emphasis on development of chimeric antigens. Significant progress was also shown on the elucidation of Treponema pallidum genomes from virtually all continents to assess the diversity in vaccine candidates of the syphilis spirochete.

Treponema pallidum genetic diversity and its implications for targeted vaccine development: A cross-sectional study of early syphilis cases in Southwestern Colombia.

BACKGROUND: Venereal syphilis, caused by the spirochete Treponema pallidum subsp. pallidum (TPA), is surging worldwide, underscoring the need for a vaccine with global efficacy. Vaccine development requires an understanding of syphilis epidemiology and clinical presentation as well as genomic characterization of TPA strains circulating within at-risk populations. The aim of this study was to describe the clinical, demographic, and molecular features of early syphilis cases in Cali, Colombia. METHODS AND FINDINGS: We conducted a cross-sectional study to identify individuals with early syphilis (ES) in Cali, Colombia through a city-wide network of public health centers, private sector HIV clinics and laboratory databases from public health institutions. Whole blood (WB), skin biopsies (SB), and genital and oral lesion swabs were obtained for measurement of treponemal burdens by polA quantitative polymerase chain reaction (qPCR) and for whole-genome sequencing (WGS). Among 1,966 individuals screened, 128 participants met enrollment criteria: 112 (87%) with secondary (SS), 15 (12%) with primary (PS) and one with early latent syphilis; 66/128 (52%) self-reported as heterosexual, while 48 (38%) were men who have sex with men (MSM). Genital ulcer swabs had the highest polA copy numbers (67 copies/µl) by qPCR with a positivity rate (PR) of 73%, while SS lesions had 42 polA copies/µl with PR of 62%. WB polA positivity was more frequent in SS than PS (42% vs 7%, respectively; p = 0.009). Isolation of TPA from WB by rabbit infectivity testing (RIT) was achieved in 5 (56%) of 9 ES WB samples tested. WGS from 33 Cali patient samples, along with 10 other genomic sequences from South America (9 from Peru, 1 from Argentina) used as comparators, confirmed that SS14 was the predominant clade, and that half of all samples had mutations associated with macrolide (i.e., azithromycin) resistance. Variability in the outer membrane protein (OMP) and vaccine candidate BamA (TP0326) was mapped onto the protein's predicted structure from AlphaFold. Despite the presence of mutations in several extracellular loops (ECLs), ECL4, an immunodominant loop and proven opsonic target, was highly conserved in this group of Colombian and South American TPA isolates. CONCLUSIONS: This study offers new insights into the sociodemographic and clinical features of venereal syphilis in a highly endemic area of Colombia and illustrates how genomic sequencing of regionally prevalent TPA strains can inform vaccine development.

Clinical presentation of early syphilis and genomic sequences of Treponema pallidum strains in patient specimens and isolates obtained by rabbit inoculation.

BACKGROUND: The global resurgence of syphilis necessitates vaccine development. METHODS: We collected ulcer exudates and blood from 17 primary syphilis (PS) participants and skin biopsies and blood from 51 secondary syphilis (SS) participants in Guangzhou, China for Treponema pallidum subsp. pallidum (TPA) qPCR, whole genome sequencing (WGS), and isolation of TPA in rabbits. RESULTS: TPA DNA was detected in 15 of 17 ulcer exudates and 3 of 17 blood PS specimens. TPA DNA was detected in 50 of 51 SS skin biopsies and 27 of 51 blood specimens. TPA was isolated from 47 rabbits with success rates of 71% (12/17) and 69% (35/51), respectively, from ulcer exudates and SS bloods. We obtained paired genomic sequences from 24 clinical samples and corresponding rabbit isolates. Six SS14- and two Nichols-clade genome pairs contained rare discordances. Forty-one of the 51 unique TPA genomes clustered within SS14 subgroups largely from East Asia, while 10 fell into Nichols C and E subgroups. CONCLUSIONS: Our TPA detection rate was high from PS ulcer exudates and SS skin biopsies and over 50% from SS blood, with TPA isolation in over two-thirds of samples. Our results support the use of WGS from rabbit isolates to inform vaccine development.

The incidence of new cases of syphilis has skyrocketed globally in the twenty-first century. This global resurgence requires new strategies, including vaccine development. As part of an NIH funded Cooperative Research Center to develop a syphilis vaccine, we established a clinical research site in Guangzhou, China to better define the local syphilis epidemic and obtain samples from patients with primary and secondary syphilis for whole genome sequencing (WGS) of circulating Treponema pallidum strains. Inoculation of rabbits enabled us to obtain T. pallidum genomic sequences from spirochetes disseminating in blood, a compartment of immense importance for syphilis pathogenesis. Collectively, our results further clarify the molecular epidemiology of syphilis in southern China, enrich our understanding of the manifestations of early syphilis, and demonstrate that the genomic sequences of spirochetes obtained by rabbit inoculation accurately represent those of the spirochetes infecting the corresponding patients.

Early syphilis in Guangzhou, China: presentation, molecular detection of Treponema pallidum , and genomic sequences in clinical specimens and isolates obtained by rabbit infectivity testing.

Background: The global resurgence of syphilis requires novel prevention strategies. Whole genome sequencing (WGS) of Treponema pallidum ( TPA ) using different specimen types is essential for vaccine development. Methods: Patients with primary (PS) and secondary (SS) syphilis were recruited in Guangzhou, China. We collected ulcer exudates and blood from PS participants, and skin biopsies and blood from SS participants for TPA polA polymerase chain reaction (PCR); ulcer exudates and blood were also used to isolate TPA strains by rabbit infectivity testing (RIT). TPA WGS was performed on 52 ulcer exudates and biopsy specimens and 25 matched rabbit isolates. Results: We enrolled 18 PS and 51 SS participants from December 2019 to March 2022. Among PS participants, TPA DNA was detected in 16 (89%) ulcer exudates and three (17%) blood specimens. Among SS participants, TPA DNA was detected in 50 (98%) skin biopsies and 27 (53%) blood specimens. TP A was isolated from 48 rabbits, with a 71% (12/17) success rate from ulcer exudates and 69% (36/52) from SS bloods. Twenty-three matched SS14 clade genomes were virtually identical, while two Nichols clade pairs had discordant tprK sequences. Forty-two of 52 unique TPA genomes clustered in an SS14 East Asia subgroup, while ten fell into two East Asian Nichols subgroups. Conclusions: Our TPA detection rate was high from PS ulcer exudates and SS skin biopsies and over 50% from SS whole blood, with RIT isolation in over two-thirds of samples. Our results support the use of WGS from rabbit isolates to inform vaccine development. Summary: We performed Treponema pallidum molecular detection and genome sequencing from multiple specimens collected from early syphilis patients and isolates obtained by rabbit inoculation. Our results support the use of whole genome sequencing from rabbit isolates to inform syphilis vaccine development.

Clinical and genomic diversity of Treponema pallidum subsp. pallidum: A global, multi-center study of early syphilis to inform vaccine research.

Background: The continuing increase in syphilis rates worldwide necessitates development of a vaccine with global efficacy. We conducted a multi-center, observational study to explore Treponema pallidum subsp. pallidum ( TPA ) molecular epidemiology essential for vaccine research by analyzing clinical data and specimens from early syphilis patients using whole-genome sequencing (WGS) and publicly available WGS data. Methods: We enrolled patients with primary (PS), secondary (SS) or early latent (ELS) syphilis from clinics in China, Colombia, Malawi and the United States between November 2019 - May 2022. Inclusion criteria included age ≥18 years, and syphilis confirmation by direct detection methods and/or serological testing. TPA detection and WGS were conducted on lesion swabs, skin biopsies/scrapings, whole blood, and/or rabbit-passaged isolates. We compared our WGS data to publicly available genomes, and analysed TPA populations to identify mutations associated with lineage and geography. Findings: We screened 2,820 patients and enrolled 233 participants - 77 (33%) with PS, 154 (66%) with SS, and two (1%) with ELS. Median age of participants was 28; 66% were cis -gender male, of which 43% reported identifying as "gay", "bisexual", or "other sexuality". Among all participants, 56 (24%) had HIV co-infection. WGS data from 113 participants demonstrated a predominance of SS14-lineage strains with geographic clustering. Phylogenomic analysis confirmed that Nichols-lineage strains are more genetically diverse than SS14-lineage strains and cluster into more distinct subclades. Differences in single nucleotide variants (SNVs) were evident by TPA lineage and geography. Mapping of highly differentiated SNVs to three-dimensional protein models demonstrated population-specific substitutions, some in outer membrane proteins (OMPs) of interest. Interpretation: Our study involving participants from four countries substantiates the global diversity of TPA strains. Additional analyses to explore TPA OMP variability within strains will be vital for vaccine development and improved understanding of syphilis pathogenesis on a population level. Funding: National Institutes of Health, Bill and Melinda Gates Foundation.

Utility of Urine Cultures During Febrile Neutropenia Workup in Hematopoietic Stem Cell Transplantation Recipients Without Urinary Symptoms.

The utility of obtaining screening urine cultures for febrile neutropenia (FN) during hematopoietic stem cell transplant (HCT) is unknown. In 667 adult HCT patients with FN, only 40 (6%) were found with bacteriuria. Antibiotics were modified in 3 patients (0.4%) based on urine cultures and none developed urinary-associated infectious complications.

Ten Years of Disseminated Gonococcal Infections in North Carolina: A Review of Cases From a Large Tertiary Care Hospital.

BACKGROUND: The detection and reporting of disseminated gonococcal infection (DGI) has been increasing across the United States. METHODS: We conducted a retrospective chart review of DGI case-patients diagnosed between 2010 and 2019 at a large tertiary care hospital in North Carolina. RESULTS: We identified 12 DGI case-patients (7 men and 5 women, aged 20 to 44 years), of whom 5 had Neisseria gonorrheae isolated from a sterile site (confirmed), 2 had N. gonorrheae detected at a nonsterile mucosal site and had clinical manifestations consistent with DGI (probable), and 5 did not have N. gonorrheae isolated from any site, but DGI was the most likely diagnosis (suspect). Among the 12 DGI case-patients, the most common manifestation was arthritis or tenosynovitis (n = 11); 1 patient had endocarditis. Half of the patients had significant underlying comorbidities or predisposing factors, including complement deficiency. Eleven of the 12 case-patients were hospitalized, and 4 required surgical intervention. CONCLUSIONS: This case series highlights the difficulty of making a definitive diagnosis of DGI, which could negatively affect reporting to public health authorities and hinder surveillance efforts to determine the true prevalence of DGI. A high index of suspicion is required, and a full diagnostic workup should be pursued in all cases of suspected DGI.

High-throughput nanopore sequencing of Treponema pallidum tandem repeat genes arp and tp0470 reveals clade-specific patterns and recapitulates global whole genome phylogeny.

Sequencing of most Treponema pallidum genomes excludes repeat regions in tp0470 and the tp0433 gene, encoding the acidic repeat protein (arp). As a first step to understanding the evolution and function of these genes and the proteins they encode, we developed a protocol to nanopore sequence tp0470 and arp genes from 212 clinical samples collected from ten countries on six continents. Both tp0470 and arp repeat structures recapitulate the whole genome phylogeny, with subclade-specific patterns emerging. The number of tp0470 repeats is on average appears to be higher in Nichols-like clade strains than in SS14-like clade strains. Consistent with previous studies, we found that 14-repeat arp sequences predominate across both major clades, but the combination and order of repeat type varies among subclades, with many arp sequence variants limited to a single subclade. Although strains that were closely related by whole genome sequencing frequently had the same arp repeat length, this was not always the case. Structural modeling of TP0470 suggested that the eight residue repeats form an extended α-helix, predicted to be periplasmic. Modeling of the ARP revealed a C-terminal sporulation-related repeat (SPOR) domain, predicted to bind denuded peptidoglycan, with repeat regions possibly incorporated into a highly charged ß-sheet. Outside of the repeats, all TP0470 and ARP amino acid sequences were identical. Together, our data, along with functional considerations, suggests that both TP0470 and ARP proteins may be involved in T. pallidum cell envelope remodeling and homeostasis, with their highly plastic repeat regions playing as-yet-undetermined roles.

Summary of the Fourth Annual American Sexually Transmitted Diseases Association Workshop on Improving Sexually Transmitted Infection Control Efforts Through Cross-Sector Collaboration.

ABSTRACT: The American Sexually Transmitted Diseases Association has, for several years, been conducting a cross-sector workshop to bring together a variety of stakeholders to develop ideas for collaboratively improving the sexually transmitted infection control efforts in the United States. In this summary, we share the content of discussions and ideas of the fourth annual workshop for future research and potential changes to practice with a focus on diagnostic capacity.

A prospective study of asymptomatic SARS-CoV-2 infection among individuals involved in academic research under limited operations during the COVID-19 pandemic.

BACKGROUND: Early in the pandemic, transmission risk from asymptomatic infection was unclear, making it imperative to monitor infection in workplace settings. Further, data on SARS-CoV-2 seroprevalence within university populations has been limited. METHODS: We performed a longitudinal study of University research employees on campus July-December 2020. We conducted questionnaires on COVID-19 risk factors, RT-PCR testing, and SARS-CoV-2 serology using an in-house spike RBD assay, laboratory-based Spike NTD assay, and standard nucleocapsid platform assay. We estimated prevalence and cumulative incidence of seroconversion with 95% confidence intervals using the inverse of the Kaplan-Meier estimator. RESULTS: 910 individuals were included in this analysis. At baseline, 6.2% (95% CI 4.29-8.19) were seropositive using the spike RBD assay; four (0.4%) were seropositive using the nucleocapsid assay, and 44 (4.8%) using the Spike NTD assay. Cumulative incidence was 3.61% (95% CI: 2.04-5.16). Six asymptomatic individuals had positive RT-PCR results. CONCLUSIONS: Prevalence and incidence of SARS-CoV-2 infections were low; however, differences in target antigens of serological tests provided different estimates. Future research on appropriate methods of serological testing in unvaccinated and vaccinated populations is needed. Frequent RT-PCR testing of asymptomatic individuals is required to detect acute infections, and repeated serosurveys are beneficial for monitoring subclinical infection.

Diagnosis and Management of Trichomonas vaginalis: Summary of Evidence Reviewed for the 2021 Centers for Disease Control and Prevention Sexually Transmitted Infections Treatment Guidelines.

Trichomonas vaginalis is likely the most prevalent nonviral sexually transmitted infection, affecting an estimated 3.7 million women and men in the United States. Health disparities are prominent in the epidemiology of trichomoniasis, as African Americans are >4 times more likely to be infected than persons of other races. Since publication of the 2015 Centers for Disease Control and Prevention sexually transmitted diseases treatment guidelines, additional data have bolstered the importance of T. vaginalis infection sequelae in women, including increased risk of human immunodeficiency virus (HIV) acquisition, cervical cancer, preterm birth, and other adverse pregnancy outcomes. Less is known about the clinical significance of infection in men. Newly available diagnostic methods, including point-of-care assays and multiple nucleic acid amplification tests, can be performed on a variety of genital specimens in women and men, including urine, allowing more accurate and convenient testing and screening of those at risk for infection. Repeat and persistent infections are common in women; thus, rescreening at 3 months after treatment is recommended. In vitro antibiotic resistance to 5-nitroimidazole in T. vaginalis remains low (4.3%) but should be monitored. High rates of T. vaginalis among sexual partners of infected persons suggest a role for expedited partner treatment. A randomized controlled trial in HIV-uninfected women demonstrated that multidose metronidazole 500 mg twice daily for 7 days reduced the proportion of women with Trichomonas infection at 1 month test of cure compared with women receiving single-dose therapy (2 g). The 2-g single-dose oral metronidazole regimen remains the preferred treatment in men.

Coinfection With Chlamydial and Gonorrheal Infection Among US Adults With Early Syphilis.

ABSTRACT: Among 865 adults with early syphilis considered for a multicenter treatment trial, 234 (27%) were excluded before enrollment because of bacterial sexually transmitted infection coinfection. Coinfection with Neisseria gonorrhoeae (29%), Chlamydia trachomatis (22%), or both (23%) was common. Study findings highlight the need for comprehensive bacterial sexually transmitted infection screening in patients with syphilis.

Costs Associated With Incorporation of Network Approaches Into Sexually Transmitted Disease Program Activities.

BACKGROUND: Network approaches can be used to study sociosexual partnerships and identify individuals at high risk of infection. Little is known about the cost structure of these services and their association with STD diagnoses. METHOD: We collected costs associated with using a peer network strategy to recruit men who have sex with men and transwomen of color in 4 counties in North Carolina: Guilford, Forsyth, Durham, and Wake from February through October 2019. We used a comprehensive costing approach to gather detailed retrospective information on the intervention cost, broken down by category and programmatic activity. RESULTS: The sociosexual networks collected consisted of 31 initial seeds (index cases) and 49 peers of those seeds. In peers, 5 cases of human immunodeficiency virus (HIV) and 10 cases of syphilis were identified. The cost per case (HIV or syphilis) identified was $7325. Personnel costs accounted for 80% of total expenditures, followed by laboratory expenses (12%). Personnel cost was distributed between disease intervention specialist patient navigators (51%), nonclinical (37%), and management (12%) staff. General administration was the costliest programmatic activity (37%), followed by case management and field services (37%), and study activities (11%). The estimated average cost per patient tested was $2242. CONCLUSIONS: Finding positive peer cases in nonclinical settings is costly but may be crucial for limiting the spread of sexually transmitted diseases. The cost of staff was the major driver. This study demonstrates that using a network strategy can be a cost-effective way to identify, test, and refer patients at high risk of syphilis and HIV infections to care.

Perceptions, experiences, and preferences for partner services among Black and Latino men who have sex with men and transwomen in North Carolina.

OBJECTIVES: In the United States, sexually transmitted infections (STIs) disproportionately affect men who have sex with men (MSM) and transwomen of color. Partner services can prevent STI transmission by facilitating testing and treatment for partners of individuals diagnosed with an STI. Understanding client perspectives towards partner services is critical to their acceptance and uptake. This study examined perceptions, experiences, and preferences for partner services among Black and Latino MSM and transwomen in North Carolina. DESIGN: We conducted seven audio-recorded focus groups in English (n = 5) and Spanish (n = 2). The audio was transcribed verbatim and we inductively analyzed data using field notes, systematic coding, and thematic comparison. RESULTS: Black MSM reported the most exposure and experiences with partner services, and most perceived partner services negatively. Feeling supported and having flexibility characterized positive experiences with partner services among Black MSM; feeling judged or harassed characterized negative experiences. Black transwomen had less exposure to partner services and had a mix of positive reactions to the approach, along with concerns about client confidentiality. Most Latino participants were unaware of partner services and expressed openness to their potential. All participants preferred self-notifying and wanted flexible, discreet, supportive partner services with linkages to other wellness resources. CONCLUSION: Building off positive partner services experiences and responding to client preferences can enhance trust, acceptability, and service use.

Intersection of Syphilis and Human Immunodeficiency Virus (HIV) Networks to Identify Opportunities to Enhance HIV Prevention.

BACKGROUND: Human immunodeficiency virus (HIV) and syphilis infection continue at disproportionate rates among minority men who have sex with men (MSM) in the United States. The integration of HIV genetic clustering with partner services can provide important insight into local epidemic trends to guide interventions and control efforts. METHODS: We evaluated contact networks of index persons defined as minority men and transgender women diagnosed with early syphilis and/or HIV infection between 2018 and 2020 in 2 North Carolina regions. HIV clusters were constructed from pol sequences collected through statewide surveillance. A combined "HIV-risk" network, which included persons with any links (genetic or sexual contact) to HIV-positive persons, was evaluated by component size, demographic factors, and HIV viral suppression. RESULTS: In total, 1289 index persons were identified and 55% named 1153 contacts. Most index persons were Black (88%) and young (median age 30 years); 70% had early syphilis and 43% had prevalent HIV infection. Most people with HIV (65%) appeared in an HIV cluster. The combined HIV-risk network (1590 contact network and 1500 cluster members) included 287 distinct components; however, 1586 (51%) were in a single component. Fifty-five percent of network members with HIV had no evidence of viral suppression. Overall, fewer index persons needed to be interviewed to identify 1 HIV-positive member without viral suppression (1.3 vs 4.0 for contact tracing). CONCLUSIONS: Integration of HIV clusters and viral loads illuminate networks with high HIV prevalence, indicating recent and ongoing transmission. Interventions intensified toward these networks may efficiently reach persons for HIV prevention and care re-engagement.

Beyond Disease Intervention: Exploring an Expanded Role for Partner Services in the MATRix-NC Demonstration Project.

BACKGROUND: Disease intervention specialists (DIS) provide partner services for sexually transmitted infections (STIs). We assessed an expansion of DIS services for clients with HIV and/or syphilis, and contacts within their social and sexual networks. METHODS: Black and Latinx cisgender men and transgender women who have sex with men diagnosed with HIV and/or syphilis in 4 urban North Carolina counties were referred to designated DIS, who were trained to recruit clients as "seeds" for chain-referral sampling of sociosexual network "peers." All received HIV/STI testing and care; referrals for preexposure prophylaxis (PrEP) and social, behavioral, and non-STI medical services were offered. Participants completed baseline, 1-month, and 3-month computerized surveys. RESULTS: Of 213 cases referred to DIS from May 2018 to February 2020, 42 seeds (25 with syphilis, 17 with HIV) and 50 peers participated. Median age was 27 years; 93% were Black and 86% were cisgender men. Most peers came from seeds' social networks: 66% were friends, 20% were relatives, and 38% were cisgender women. Incomes were low, 41% were uninsured, and 10% experienced recent homelessness. More seeds than peers had baseline PrEP awareness; attitudes were favorable, but utilization was poor. Thirty-seven participants were referred for PrEP 50 times; 17 (46%) accessed PrEP by month 3. Thirty-nine participants received 129 non-PrEP referrals, most commonly for housing assistance, primary care, Medicaid navigation, and food insecurity. CONCLUSIONS: Chain-referral sampling from partner services clients allowed DIS to access persons with significant medical and social service needs, demonstrating that DIS can support marginalized communities beyond STI intervention.

Daily Predictors of ART Adherence Among Young Men Living with HIV Who Have Sex with Men: A Longitudinal Daily Diary Study.

Improving adherence to antiretroviral therapy (ART) is essential for limiting HIV disease progression among young sexual minority men living with HIV. Daily diaries allow for a detailed examination of how fluctuations in psychosocial factors are associated with adherence over time. Across three cities in the United States, this study collected 60 days of quantitative data from 44 young men (between 16 and 24 years of age) living with HIV who have sex with men. Lagged transition models explored the associations of mood, stress, social support, substance use, and condomless intercourse with daily ART adherence. Baseline levels of illicit substance use and condomless intercourse, and a higher proportion of days with stress or marijuana use, were associated with lower ART adherence. Lapses in adherence predicted non-adherence the following day. Findings suggest prospective data collection may identify different predictors of adherence compared to retrospective recall. Lapse-management strategies are needed to improve adherence following a missed dose.

Bacterial Vaginosis and Its Association With Incident Trichomonas vaginalis Infections: A Systematic Review and Meta-Analysis.

BACKGROUND: Bacterial vaginosis (BV) has been associated with an increased risk for acquisition of human immunodeficiency virus and sexually transmitted infections. We evaluated the association between BV and incident Trichomonas vaginalis (TV) infection in women. METHODS: MEDLINE and ClinicalTrials.gov were searched for articles published between January 1, 1980, and May 7, 2021. Observational studies in women that evaluated the relationship between having/not having BV and the risk for acquiring TV were included. RESULTS: Fourteen studies were included in the systematic review; 12 studies were included in meta-analyses involving 18,424 participants. Most studies used Nugent scoring to diagnose BV. For TV diagnosis, 12 studies used wet mount microscopy or culture, and 2 used nucleic acid amplification tests. There was diversity in the measures of association used, so an overall effect size could not be calculated. The majority of studies reported odds ratios, which showed an increased risk of incident TV among women with BV versus without BV (adjusted odds ratio, 1.87; 95% confidence interval, 1.45-2.40; P = 0.007). However, there were heterogeneity and potential confounding factors (eg, age, sexual partners) reported among studies. CONCLUSIONS: This systematic review and meta-analysis provide evidence for a nearly 2-fold higher risk for acquiring TV among women with BV compared with women without BV.

Research Priorities to End the Adolescent HIV Epidemic in the United States: Viewpoint.

Youth represent 21% of new HIV diagnoses in the United States. Gay, bisexual, and transgender (GBT) youth, particularly those from communities of color, and youth who are homeless, incarcerated, in institutional settings, or engaging in transactional sex are most greatly impacted. Compared with adults, youth have lower levels of HIV serostatus awareness, uptake of antiretroviral therapy (ART), and adherence. Widespread availability of ART has revolutionized prevention and treatment for both youth at high risk for HIV acquisition and youth living with HIV, increasing the need to integrate behavioral interventions with biomedical strategies. The investigators of the Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) completed a research prioritization process in 2019, focusing on research gaps to be addressed to effectively control HIV spread among American youth. The investigators prioritized research in the following areas: (1) innovative interventions for youth to increase screening, uptake, engagement, and retention in HIV prevention (eg, pre-exposure prophylaxis) and treatment services; (2) structural changes in health systems to facilitate routine delivery of HIV services; (3) biomedical strategies to increase ART impact, prevent HIV transmission, and cure HIV; (4) mobile technologies to reduce implementation costs and increase acceptability of HIV interventions; and (5) data-informed policies to reduce HIV-related disparities and increase support and services for GBT youth and youth living with HIV. ATN's research priorities provide a roadmap for addressing the HIV epidemic among youth. To reach this goal, researchers, policy makers, and health care providers must work together to develop, test, and disseminate novel biobehavioral interventions for youth.